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Ethnopharmacological Relevance: Phyllanthus muellerianus (Kunze) Exell, a member of the Phyllanthaceae family, is a medicinal plant widely distributed in Africa. Decoctions from the leaves are used in Nigeria to treat fevers, convulsions, some neurological disorders and malaria., Aim of the Study: This study is to evaluate the anti-malarial properties of methanol extract of Phyllanthus muellerianus (MEPM) leaves and its ethyl acetate fraction using a murine malaria model infected with Plasmodium berghei. Additionally, we seek to investigate the potential modulatory effects of this extract and fraction on CD4 + T-cell populations in the context of malaria infection., Materials and Methods: The anti-malarial effects of the leaf methanol extract of Phyllanthus muellerianus (MEPM) were screened using three established in vivo models of anti-plasmodial screening namely the curative, suppressive and prophylactic models. The methanol extract (MEPM) was afterwards fractionated into hexane (HFPM), ethyl acetate (EAFPM), and methanol (MFPM) fractions. In the pilot anti-malarial screening of the fractions, EAFPM exhibited the best antiparasitic activity. Subsequently, EAFPM was screened for anti-malarial activity using the three models above. The effects of the MEPM and EAFPM on haematological indices (Hb and PCV) of the inoculated animals were further screened and the mean survival time (MST) of the animals was monitored. CD4 + T cells of various groups were counted before and after treatment using a flow cytometer. The EAFPM was further subjected to HPLC analysis for identification of its major compounds., Results: The EAFPM (100 and 200 mg/kg) elicited 88% and 93% cure respectively in the curative model, while artesunate (5 mg/kg,- the positive control) gave 87% protection. The MEPM and EAFPM also gave significant suppression of parasitemia in the suppressive model. The treated groups survived beyond 28 days as against 11 days by the control group (infected but not treated). The treated groups also prevented anaemia seen in the negative control. The EAFPM group significantly modulated the CD4 + T cell. Compounds identified were Gallocatechin, Quercetin -3-O-gallate, Ellagic acid, and Methylellagic acid rhamnoside)., Conclusion: The study established that the leaf of Phyllanthus muellerianus possesses antimalarial activity, thus lending support to its use in the folkloric treatment of malaria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alopecia areata (AA) is an autoimmune-induced hair loss condition, by utilizing MNX, a hair growth-promoting compound. However, minoxidil (MNX) administration's efficacy is hindered by low bioavailability and adverse effects. To enhance its delivery, Trilayer Dissolving Microneedles (TDMN) are introduced, enabling controlled drug release. The study's primary was to establish a validated UV-Vis Spectrophotometer method for Minoxidil analysis in rat skin affected by alopecia areata. This method adheres to International Conference Harmonization (ICH) and FDA guidelines, encompassing accuracy, precision, linearity, quantification limit (QL), and detection limit (DL). The validation method was conducted through two approaches, namely UV region validation using PBS and the colorimetric method in the visible region (Vis). The validated approach is then employed for assessing in vitro release, ex vivo permeation, and in vivo pharmacokinetics. Results indicate superior MNX extraction recovery using methanol compared to acetonitrile. Method C (5mL methanol) is optimal, offering high recovery with minimal solvent usage. Precision assessments demonstrate %RSD values within MNX guidelines (≤15%), affirming accuracy and reproducibility. UV-Vis spectroscopy quantifies MNX integration into TDMN, using PVA-PVP, with concentrations aligning with ICH standards (95% to 105%). In conclusion, TDMN holds promise for enhancing MNX delivery, mitigating bioavailability and side effect challenges. The validated UV-Vis Spectrophotometer method effectively analyzes MNX in skin tissues, providing insights into AA treatment and establishing a robust analytical foundation for future studies., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Acute methanol intoxication, whether unintentional or deliberate, necessitates prompt intervention to prevent severe morbidity and mortality. Homemade alcoholic beverages are a frequent source of such poisoning. This retrospective analysis examined two outbreaks of methanol intoxication in Saudi Arabia. It investigated the clinical presentation, implemented management strategies, and any lasting complications (sequelae) associated with these cases. The aim was to assess the potential impact of different treatment modalities and the timeliness of their initiation on patient outcomes., Methods: This was a retrospective case series of methanol poisoning cases which presented to the adult emergency department (ED) at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. There were two separate outbreaks in the city, the first one was from September 1 to September 10, 2020 and the second one was from May 14 to May 20, 2021. Electronic charts were reviewed, and data were extracted to previously prepared data extraction sheets., Result: From the 22 patients who arrived in the ED alive, the most common complaints were nausea or vomiting followed by altered level of consciousness. About 9% from the patient were hypotensive, 36% were tachycardic, 41% were tachypneic and 4% were having SpO2 < 94%. Brain CT was abnormal in 6 patients. Vision impairment was the most common sequalae of methanol poisoning (7 out of 12 patients who were assessed by ophthalmologist, 58%). When the patients were divided based on severity (mild, moderate, severe), nausea or vomiting and loss of consciousness were the most common complaints among the moderate group while loss of consciousness predominated in the severe group. Two patients presented with low blood pressure and were in the sever group. The severe group had a mean Glasgow Coma Scale (GCS) of 8. Most of the patients in the severity groups underwent the same management apart from those who died or deposited. Eight patients in the severe group had to be intubated., Conclusion: This study demonstrates the multifaceted clinical presentation of methanol poisoning, culminating in a 17.4% mortality rate. Notably, our findings emphasize the critical role of prompt diagnosis and swift initiation of combined fomepizole therapy and hemodialysis in mitigating mortality and minimizing the potential for chronic visual sequelae associated with methanol poisoning., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Snake bites are a critical health issue in many parts of the world particularly in Asian countries lacking efficient health facilities in rural areas. Cobra is the most common snake type in Asia and is responsible for a large number of mortalities particularly in rural areas. Plants are usually considered the most effective and easy-to-approach treatment for snake bites in rural areas of various countries. Vitex negundo L. is an important medicinal plant traditionally used to treat snake bite envenomation in many countries of Asia., Aim of the Study: From literature survey of plants traditionally used in the treatment of snake bites in Asian countries including India, Pakistan and Sri Lanka, roots of V. negundo were selected for the present study. Anti-snake venom potential of its roots was assessed through various in vitro assays targeting the phospholipase A 2 enzyme., Materials and Methods: V. negundo roots were sequentially extracted in different organic solvents to get fractions and in methanol to get total extract. The extracts were evaluated for phospholipase A 2 (PLA 2 ) inhibitory potential through inhibition of venom-induced hemolysis, ADP-induced platelet aggregation, PLA 2 -induced fatty acid hydrolysis and anticoagulant effect of cobra venom. Antioxidant power was determined using DPPH and superoxide radical scavenging assays. GC-MS and HPLC analysis was performed for the total methanol extract., Results: Strong PLA 2 inhibitory effect was observed for all the extracts. The ethyl acetate, acetone and methanol fractions significantly inhibited toxic effects of cobra venom under in vitro conditions. Radical scavenging potential of these fractions was also significantly high as compared to non-polar fractions in both DPPH and superoxide scavenging assays. Phytochemical analysis indicated high phenolic and flavonoid contents in these fractions. GC-MS and HPLC analysis of total methanol extract confirmed the presence of bis(2-ethylhexyl) phthalate, phenol, o-Guaiacol, palmitic acid-methyl ester, methyl stearate, quercetin and kaempferol in the plant., Conclusion: The study concluded that the roots of V. negundo, particularly their polar extracts, have strong PLA 2 inhibitory effect against cobra venom confirming their traditional use to manage snake bites. The roots of this plant can be further studied for isolation of plant-based antisera., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Plasmodium falciparum multi-drug resistant (MDR) strains are a great challenge to global health care. This predicament implies the urgent need to discover novel antimalarial drugs candidate from alternative natural sources. The Himalaya constitute a rich repository of medicinal plants which have been used traditionally in the folklore medicine since ages and having no scientific evidence for their activity. Crambe kotschyana Boiss. and Eremurus himalaicus Baker are used for their antipyretic and hepatoprotective properties in Kinnaur district of Himachal Pradesh, India., Aim of the Study: This study would investigate the antiplasmodial efficacy of C. kotschyana and E. himalaicus extracts, their fractions and active components using in vitro, in vivo and in silico approaches to provide a scientific insight into their activity., Methods: The methanol extracts of C. kotschyana (CKME) and E. himalaicus (EHME) were prepared by maceration followed by fractionation using ethyl acetate. The isolation of flavonoid glycosides isorhamnetin-3, 7-di-O-glucoside from C. kotschyana and luteolin-6-C-glucoside (isoorientin) from E. himalaicus was carried out by antiplasmodial activity-guided isolation. In vitro antimalarial activity was assessed by WHO method while in vitro cytotoxicity was ascertained employing the MTT assay. Molecular docking and molecular dynamics simulation were performed using the Glide module of Schrödinger Software and Gromacs-2022 software package respectively. In vivo curative activity was assessed by Ryley and Peters method., Results: The methanol extracts of both the plants illustrated the best antiplasmodial activity followed by the ethyl acetate fractions. Iso-orientin (IC 50 6.49 μg/ml) and Isorhamnetin-3,7-di-O-glucoside (IC 50 9.22 μg/ml) illustrated considerable in vitro activity even against P. falciparum resistant strain. Extracts/fractions as well as the isolated compounds were found to be non-toxic with CC 50  > 640 μg/ml. Molecular docking studies were performed with these 2 O-glucosides against four malaria targets to understand the binding pose of these molecules and the results suggested that these molecules have selectivity for lactate dehydrogenase enzyme. CKME and EHME exhibited curative activity in vivo along with increase in Mean Survival Time of mice., Conclusion: The research delineated the scientific evidence that both the therapeutic herbs possessed antimalarial activity and notably, bioactive compounds responsible to exhibit the antimalarial activity have been isolated, identified and characterized. Further studies are underway to assess the antiplasmodial efficacy of isolated compounds alone and in combination with standard antimalarials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives : Diabetes mellitus is a chronic metabolic disease associated with several complications, including that of kidney disease. Plant-based dietary products have shown promise in mitigating these effects to improve kidney function and prevent tissue damage. This study assessed the possible favorable effects of beetroot extract (BE) in improving kidney function and preventing tissue damage in diabetic rats. Materials and Methods : Type 2 diabetes mellitus (T2DM) was induced using a low dose of streptozotocin (STZ). Both control and rats with pre-established T2DM were divided into six groups (each consisting of eight rats). All treatments were given by gavage and continued for 12 weeks. Fasting blood glucose levels, serum fasting insulin levels, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), serum triglycerides, cholesterol, low-density lipoprotein-cholesterol, serum and urinary albumin, and creatinine and urea levels were measured. Apart from this, glutathione, malondialdehyde, superoxide dismutase, tumor necrosis factor-α, and interleukine-6 in the kidney homogenates of all groups of rats were measured, and the histopathological evaluation of the kidney was also performed. Results : It was observed that treatment with BE increased body weight significantly ( p ≤ 0.05) to be similar to that of control groups. Fasting glucose, insulin, HOMA-IR levels, and lipid profile in the plasma of the pre-established T2DM rats groups decreased to p ≤ 0.05 in the BE-treated rats as the BE concentration increased. Treatment with BE also improved the renal levels of oxidative stress and inflammatory markers, urinary albumin, and serum creatinine and urea levels. Unlike all other groups, only the kidney tissues of the T2DM + BE (500 mg/kg) rats group showed normal kidney tissue structure, which appears to be similar to those found in the kidney tissues of the control rats groups. Conclusion : we found that streptozotocin administration disturbed markers of kidney dysfunction. However, Beta vulgaris L. root extract reversed these changes through antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Ethnopharmacological Relevance: Having identified Annickia affinis as the most potent antiplasmodial plant constituent in a hepta-herbal Agbo-iba (HHA) formula commonly used to manage malaria in Benin city, Nigeria, we have in this study attempted to identify the specialized metabolites responsible for antiplasmodial activity of A. affinis through anti-blood stage malaria parasite activity guided isolation of potent molecules from its stem bark methanol extract. After that, phenotypic effects, including stage-specific kill kinetics, were investigated. Further, the crude extract, its potent fractions, and specialized metabolites were also tested against the liver-stage malaria parasite., Materials and Methods: A. affinis was subjected to molecular PCR-based analysis to confirm its identity. Thereafter, extraction of its stem bark with methanol was carried out. Alkaloid enriched fractions from this stem bark extract were obtained using the acid-base-solvent extraction method. These alkaloid-enriched fractions were subjected to various chromatographic techniques that led to the isolation of two protoberberine alkaloids identified as berberine and palmatine based on NMR and mass spectrometry analysis. The efficacy of crude extract, fractions and purified alkaloids was tested against the malaria parasite's blood and liver stages, respectively., Results and Discussion: Annickia affinis methanol extract, fractions, and the isolated protoberberine alkaloids showed excellent antiplasmodial activity with good selectivity against blood-stage malaria parasite. Thus, their IC 50 against various strains of the parasite ranged from 0.95 to 18.65 μg/ml, while CC 50 against Human embryonic kidney (HEK) and the human hepatoma (HUH-7) cell lines ranged between 10 and > 100 μg/ml. Interestingly, the crude extract and the alkaloid enriched fractions showed promising activity against the liver-stage malaria parasite. Between berberine and palmatine isolated from the potent fractions, only the former showed ∼100% and 90% inhibitions of liver stage parasite at 5 μg/ml and 1 μg/ml, respectively, while the latter showed no inhibition even at 20 μg/ml., Conclusion: This study reports that the ethnomedicinal use of HHA to manage malaria can be attributed to the presence of promising antiplasmodial protoberberine alkaloids together with synergistic effects via either enhancement of bioavailability or improved pharmacokinetics by other phytoconstituent(s) coming from other HHA constituent plants. The protoberberine alkaloids isolated have been identified as fast-acting antiplasmodial agents, with activity against all erythrocytic stages of the malaria parasite. Further, A. affinis methanol stembark extract and the protoberberine alkaloid berberine isolated from it also displayed excellent activity (>90% inhibition at 1 μg/ml) against the liver-stage malaria parasite. A. affinis and HHA can thus be useful as both liver-stage prophylactic and blood-stage curative agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Eclipta prostrata (L.) L. is a medicinal plant used by many ethnic groups in Brazil to treat respiratory diseases, hepatitis and the bites of venomous animals. A methanolic extract of E. prostrata (MEEP), the major components of which are wedelolactone (WED) and demethylwedelolactone (DMW), exhibited anti-inflammatory activity in acute asthma models but the effects on lung inflammation and the mechanisms of action of MEEP in a chronic asthma model are not known., Aim of the Study: To study the effects of MEEP in vivo using a chronic ovalbumin (OVA)-induced allergic asthma model in mice., Materials and Methods: The identities of WED and DMW in MEEP were confirmed and the concentrations determined by liquid chromatography and tandem mass spectrometry. Male Balb/c mice were sensitized and challenged with OVA and experimental animals were treated with MEEP (100, 250 or 500 mg/kg) while control animals were treated with dexamethasone (2 mg/kg) or normal saline. Bronchial hyperresponsiveness, total and differential cell counts in bronchoalveolar lavage (BAL), and the production of Th2 cytokines in lung homogenates were assessed. Lung inflammation and mucus production were evaluated by histological analysis while nuclear factor kappa-B (NF-κB) activation was assessed immunohistochemically., Results: Concentrations of WED and DMW in MEEP were 5.12% and 1.04%, respectively. Treatments with MEEP (250 or 500 mg/kg) significantly decreased bronchial hyperresponsiveness, reduced total cell and eosinophil counts in BAL and IL-4 concentrations in lung homogenate, and inhibited NF-κB activation. Treatment with MEEP at 500 mg/kg reduced the level of IL-5 in lung homogenates but did not decrease IL-13 concentration or mucus production., Conclusions: MEEP attenuated bronchial hyperresponsiveness and decreased lung and airway inflammation in a chronic asthma model in mice. The mechanism of action involves inhibition of NF-κB activation, most likely associated with the presence of the coumestans WED and DMW. These results support the ethnopharmacological evidence for the use of E. prostrata against asthma and other respiratory inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Significant risk factors for atherosclerosis include hyperlipidemia and oxidative stress, which together rank as three of the most significant risk factors for cardiovascular diseases. Securigera securidaca lowers cholesterol levels in diabetic rats' blood. This investigation's objective was to determine how methanolic extracts affected the flowers, leaves, and seeds of plants in rats that were fed a high-fat diet (HFD). Five groups of animals were created (n = 5). A total of 35 days, divided into two intervals, were used for the study. Rats received HFD during the first 15-day interval, while during the second 20-day interval, they also received extracts or the Atorvastatin reference drug. The extract of seeds has a high phenol content as well as DPPH radical antioxidant activity. Extracts were given at a dose of 200 mg/kg; p.o. Methanolic treatment of S. securidaca flowers, leaves, and seeds in HFD-induced hyperlipidemic rats resulted in significant reductions in total cholesterol, triglycerides, LDLC, and VLDL-C levels. HDL-C levels increased significantly because of the leaves. While in hyperlipidemic rats, seeds significantly reduced the activities of the enzymes ALT and ALP. The findings showed that, to a certain extent, seeds, flowers, and leaves may have benefits in reducing hyperlipidemia brought on by HFD in terms of lipid profiles and liver function enzymes. The findings of this study indicate a promising application prospect, but more research is needed to determine the exact mechanism of these novel compounds as antihyperlipidemic agents and to clarify their potential combination effect with synthetic drugs such as Atorvastatin. Combinations can reduce the dose of chemical medications required, which lowers the risk of side effects.

Ethnopharmacological Relevance: Cupressus torulosa (family Cupressaceae), widely distributed in the north western Himalayan region of India, is a coniferous aromatic tree with various traditional uses of its aerial parts. Its needles have been used for anti-inflammatory, anticonvulsant, antimicrobial, and wound-healing properties., Aim of the Study: The study aimed at investigating the previously unknown anti-inflammatory activity of the hydromethanolic extract of the needles employing in vitro and in vivo assays and scientifically validate traditional claim of their use in treatment of inflammation. Chemical characterization of the extract with the aid of UPLCQTOFMS was also of interest., Materials and Methods: C. torulosa needles were first defatted with hexane and sequentially extracted with chloroform and 25% aqueous methanol (AM). Since the presence of phenolics (TPCs, 208.21 ± 0.95 mg GAE/g needles) and flavonoids (TFCs, 84.61 ± 1.21 mg QE/g needles) was observed in the AM extract only, it was chosen for biological and chemical examinations. Acute toxicity of the AM extract on female mice was evaluated following the OECD guideline 423. In vitro anti-inflammatory activity of the AM extract was examined using egg albumin denaturation assay while carrageenan-induced paw edema and formalin-induced paw edema models at doses of 100, 200 and 400 mg/kg po were used to determine the in vivo activity of the AM extract on Wistar rats of either sex. The components of the AM extract were analyzed by UPLC-QTOF-MS method using non-targeted metabolomics approach., Results: AM extract was found to be non-toxic at 2000 mg/kg b.w. with no signs of abnormal locomotion, seizures and writhing. The extract demonstrated promising in vitro anti-inflammatory activity (IC 50 160.01 μg/mL) compared to standard diclofenac sodium (IC 50 73.94 μg/mL) in egg albumin denaturation assay. In carrageenan-induced paw edema and formalin-induced paw edema tests the extract showed significant anti- inflammatory activity (57.28% and 51.04% inhibition of paw edema, respectively) at the dose of 400 mg/kg p.o. after 4 h in comparison to the standard diclofenac sodium which displayed 61.39% and 52.90% inhibition, respectively, at the dose of 10 mg/kg p.o. after 4 h in these models. A total of 63 chemical constituents, majority of them being phenolics, were found in the AM extract of the needles. Two compounds namely monotropein (iridoid glycoside), (±)12-HETE (eicosanoid) and fraxin (coumarin glycoside) were reported to have anti-inflammatory effect., Conclusions: For the first time our study demonstrated that hydro-methanolic extract of C. torulosa needles exhibit anti-inflammatory activity thereby supporting their traditional use in the treatment of inflammatory disorders. UPLCQTOFMS assisted chemical profile of the extract was also unveiled., Competing Interests: Declaration of competing interest The authors declare that they do not have any conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Malaria is still one of the most severe public health problems worldwide. The development of treatment, prevention, and control of malaria is one of the substantial problems in the world., Aims: To investigate the in vitro antimalarial activity of Syzygium cumini methanol fruit fraction., Methods: Syzygium cumini L fruit powder was macerated with methanol (PA) and the extract obtained was fractionated using the liquid-liquid partition method with n-hexane, ethyl acetate, butanol, chloroform, methanol, and water solvents. In vitro antimalarial assay was conducted using the culture of Plasmodium falciparum 3D7 strain culture that had reached >5% growth and was examined for IC 50 values using a 24-well microplate in duplicate. Each treatment and control well contained 1,080 μl of complete media. Well, number 1 was added with 120 μl fraction, and then the solution was diluted until it reached 0.01, 0.1, 1, 10, and 100 μg/ml the final concentration in the microtiter well. The control only contained complete media and infected erythrocytes without the addition of anti-malarial drugs. The microplate was incubated for 48 hours. After 48 hours, a thin blood smear was made fixed with methanol and stained with 20% Giemsa for 20 minutes to determine the IC 50 value by plotting sample concentrations and percentage of parasitemia in Excel., Results: The IC 50 values of ethyl acetate fraction, n.hexane fraction, butanol fraction, and water fraction were 1.189, 76.996, 1,769, and 15.058 μg/ml, respectively. Whereases the IC 50 values of C1 fraction (mix fraction from chloroform: methanol 100:0 and 90:10) and C4 fraction (mix fraction from chloroform: methanol 20:80, 10:90, and 0:100) were 100.126 and 1.015 μg/ml, respectively. The results showed that the IC 50 value of ethyl acetate, butanol, and C4 fraction were lower than 10μg/ml and were considered as good activity (strong antimalarial activity)., Conclusion: The ethyl acetate, butanol and C4 subfraction from S. cumini fruit have the potential to be developed as an antimalarial agent., Competing Interests: The authors declare that there is no conflict of interest.

Background: Helminth infections are an important public health problem in humans and have an even greater impact on domestic animal and livestock welfare. Current readouts for anthelmintic drug screening assays are stage development, migration, or motility that can be subjective, laborious, and low in throughput. The aim of this study was to apply and optimize a fluorometric technique using resazurin for evaluating changes in the metabolic activity of Ascaris suum third-stage larvae (L3), a parasite of high economic relevance in swine., Methods: Ascaris suum L3 were mechanically hatched from 6- to 8-week embryonated and sucrose-gradient-enriched eggs. Resazurin dye and A. suum L3 were titrated in 96-well microtiter plates, and resazurin reduction activity was assessed by fluorometry after 24 h of incubation. Fluorescence microscopy was used to localize the resazurin reduction site within the larvae. Finally, we exposed A. suum L3 to various stress conditions including heat, methanol, and anthelmintics, and investigated their impact on larval metabolism through resazurin reduction activity., Results: We show that the non-fluorescent dye resazurin is reduced inside vital A. suum L3 to fluorescent resorufin and released into the culture media. Optimal assay parameters are 100-1000 L3 per well, a resazurin concentration of 7.5 µg/ml, and incubation at 37 °C/5% CO 2 for 24 h. An intact L2 sheath around the L3 of A. suum completely prevents the uptake of resazurin, while in unsheathed L3, the most intense fluorescence signal is observed along the larval midgut. L3 exposed to methanol or heat show a gradually decreased resazurin reduction activity. In addition, 24 h exposure to ivermectin at 0.625 µM, mebendazole at 5 µM, and thiabendazole from 10 to 100 µM significantly decreased larval metabolic activity by 55%, 73%, and 70% to 89%, respectively., Conclusions: Together, our results show that both metabolic stressors and anthelmintic drugs significantly and reproducibly reduce the resazurin reduction activity of A. suum L3, making the proposed assay a sensitive and easy-to-use method to evaluate metabolic activity of A. suum L3 in vitro., (© 2023. The Author(s).)

Ethnopharmacological Relevance: Cenchrus ciliaris L. belongs to the family Poaceae and is found all over the world. It is native to the Cholistan desert of Pakistan where it is locally known as 'Dhaman'. Owing to high nutritional value, C. ciliaris is used as fodder while seeds are used for bread making which are consumed by locals. It also possesses medicinal value and is extensively employed to treat pain, inflammation, urinary tract infection, and tumors., Aim of Study: Studies on the pharmacological activities of C. ciliaris are scarce in spite of its several traditional uses. To the best of our knowledge, no comprehensive study has been conducted on anti-inflammatory, analgesic and anti-pyretic activity of C. ciliaris until now. Here we employed an integrative phytochemical and in - vivo framework to evaluate the potential biological activities of C. ciliaris against inflammation, nociception and pyrexia experimentally induced in rodents., Material and Methods: C. ciliaris was collected from the desert of Cholistan, Bahawalpur, Pakistan. Phytochemical profiling of C. ciliaris was done by employing GC-MS analysis. Anti-inflammatory activity of plant extract was initially determined by various in - vitro assays including albumin denaturation assay and RBC membrane stabilization assays. Finally, rodents were utilized to evaluate in - vivo anti-inflammatory, antipyretic and anti-nociceptive activities., Results: Our data revealed the presence of 67 phytochemicals in methanolic extract of C. ciliaris. The methanolic extract of C. ciliaris provided RBC membrane stabilization by 65.89 ± 0.32% and protection against albumin denaturation by 71.91 ± 3.42% at 1 mg/ml concentration. In in - vivo acute inflammatory models, C. ciliaris exhibited 70.33 ± 1.03, 62.09 ± 8.98, 70.24 ± 0.95% anti-inflammatory activity at concentration of 300 mg/ml against carrageenan, histamine and serotonin induced inflammation. In CFA induced arthritis, inhibition of inflammation was found to be 48.85 ± 5.11% at 300 mg/ml dose after 28 days of treatment. In anti-nociceptive assays C. ciliaris exhibited significant analgesic activity in both peripheral and centrally mediated pain. The C. ciliaris also reduced the temperature by 75.26 ± 1.41% in yeast induced pyrexia., Conclusion: C. ciliaris exhibited anti-inflammatory effect against acute and chronic inflammation. It also showed significant anti-nociceptive and anti-pyretic activity which endorses its traditional use in the management of pain and inflammatory disorders., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As a major public health issue, cutaneous leishmaniasis (CL) has a number of complications, including drug resistance and poor response to conventional treatments. Over the last decade, research on natural sources for finding new antileishmanial agents has been a critical part of tropical disease research. Natural products also should be regarded as one of the most valuable applications for CL infection drug development. In this study, we assessed the in vitro and in vivo antileishmanial potential of Carex pendula Huds. (hanging sedge) methanolic extract and its fractions against Leishmania major produced cutaneous infection. Although the methanolic extract and its fractions exhibited suitable activity, the ethyl acetate fraction showed the best activity (with the half maximal inhibitory concentration IC 50  = 1.627 ± 0.211 mg/mL). The toxicity and selectivity indices (SI) of all samples were determined in murine peritoneal macrophage cells (J774A.1) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The flavonoid components of the ethyl acetate fraction were identified using liquid chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS). Nine chemical compounds were identified in this fraction, including three flavonols, four flavanonols, and two flavan derivatives. L. major-infected mice were used as an in vivo model because the methanolic extract was effective against L. major promastigotes in the mammalian cell line J774A.1 with SI = 2.514 (tail lesion size model). In silico analysis of identified compounds also revealed a favorable interaction between compounds 2-5 and L. major protein targets (3UIB, 4JZX, 4JZB, 5L4N, and 5L42). According to the findings of this study, the ethyl acetate fraction (as flavonoid fraction) exhibited considerable in vitro antileishmanial activity., (© 2023 John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Caesalpinia coriaria (Jacq.) Willd is widely used as a traditional medinal plant in Mexico for protective and healing purposes and the treatment of gastrointestinal diseases., Aim of the Study: To investigate the gastroprotective effect of extract of Caesalpinia coriaria pods against ethanol-induced and indomethacin-induced gastric lesion models, its anti-inflammatory and antioxidative activities, and its main compounds through LC-MS analysis., Materials and Methods: Male Wistar rats were orally administered a methanol extract obtained from the pods of C. coriaria at doses of 10, 30, 100, and 300 mg/kg prior to inducing gastric lesions with ethanol or indomethacin. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations. Determination of prostaglandin E 2 (PGE 2 ), alpha tumor necrosis factor (TNF-α), leukotriene B 4 (LTB 4 ), nitrites/nitrates, superoxide dismutase (SOD), and H 2 S gastric levels were investigated. Its main compounds of the active extract through LC-MS analysis., Results: Phenolic compounds were identified as major components of methanol extract. LC-MS analysis identified 15 constituents, and the significant compounds were gallic acid, 3-O-galloylquinic acid, digalloylglucose, tetragalloylglucose, valoneic acid dilactone, pentagalloylglucose, digalloylshikimic acid, and ellagic acid. Pretreatment with the extract at doses of 100 and 300 mg/kg significantly reduced gastric ulcer lesions in both models. Compared with the reference drugs (omeprazole or ranitidine, respectively), no significant difference was found (p < 0.05). The extract's gastroprotective effect was accompanied by significant decreases in leukocyte recruitment, and gastric levels of TNF-α and LTB 4 by two to fourfold (p < 0.05). Also, gastric levels of PGE 2 gastric levels were maintained and the antioxidant enzyme activities of SOD and nitrate/nitrite in the gastric tissue were improved (p < 0.05). The LC-MS analysis indicated the presence of hydrolyzable tannins (mainly gallic acid derivatives)., Conclusion: The results suggest that the gastroprotective effect of the methanol extract of C. coriaria pods occurs through anti-inflammatory, antioxidant, and NO modulation properties, and gallic acid derivatives may be the main possible compounds responsible for its actions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Callicarpa arborea Roxb. is widely used as traditional medicine especially by the tribal people of Bangladesh in the management of wide range of ailments. In addition to Bangladesh, the leaves of this plant is utilized as a remedy to various painful and inflammatory conditions including rheumatism, toothache and stomachache in other countries of Indian subcontinent., Aim of the Study: Depending on the ethnomedicinal uses, we undertook this study to investigate the in-vivo analgesic and anti-inflammatory activities of the methanolic extract of C. arborea Roxb. leaves in Swiss albino mice as well as its chemical composition., Materials and Methods: We evaluated the analgesic activity of Callicarpa arborea Roxb. leaves by the acetic acid induced writhing test, the hot plate test, and the formalin test. We undertook the egg albumin induced paw edema test to determine the anti-inflammatory activity of the plant. Furthermore, we conducted the phytochemical profiling by gas chromatography-mass spectrometry (GC-MS)., Results: In acute toxicity test, no mortality was observed at the highest dose of 2000 mg/kg b.w. Significant (p < 0.005) inhibition of acetic acid induced writhing was observed at both doses of the extract. A dose dependent increase in the response time was seen in the hot-plate test. In the formalin test, the extract significantly inhibited pain response in both early and late phase. We observed marked anti-inflammatory activity manifested by a significant (p < 0.005) reduction in egg albumin induced paw edema. We identified a total of twenty one compounds in the extract of by GC-MS analysis., Conclusion: Taken all into consideration we conclude that the leaves of C. arborea Roxb. possesses potent analgesic and anti-inflammatory activity, thus justifying its's ethnomedicinal use against painful and inflammatory pathological conditions., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The current study aimed to explore the in vivo therapeutic effects of the methanolic extracts of Citrullus colocynthis, Ruta graveolens, and Peganum harmala against hydatid cyst secondary infection., Methods: Aerial parts of P. harmala and R. graveolens, including leaves and stems, and seeds of C. colocynthis were collected and extracted using absolute methanol. Rats that are infected with secondary infection of hydatid cysts were treated orally and intraperitoneally according to the determined lethal doses for 30 days. Histological, hematological, and biochemical investigations were done 8 months after the infection., Results: Compared to Albendazole drug, C. colocynthis, and P. harmala, the methanol extract of R. graveolens showed higher and significant (P < 0.05) therapeutic effects on the secondary hydatid cysts growth. Those effects were represented by the reduction in the cysts' number, size, and weight; as well as the significant changes (P < 0.05) in values of hematological and biochemical parameters, the elevation of IFN-γ levels, and the decline of IL-10 and IL-4 cytokines, compared to the negative control group in both routes of treatment (oral and IP). Moreover, the histological sections showed that R. graveolens has a clear damaging effect on the hydatid cysts GL in the infected rats represented by the detachment of GL from LL and AL., Conclusion: This study can open an avenue to find new therapeutics for secondary hydatid cyst infections using the studied plant extracts, especially the extract of R. graveolens., (© 2022. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

Ethnopharmacological Relevance: The Vha-Venda people of South Africa use Pappea capensis EckI & Zeyh. (Sapindaceae) twigs to treat malaria and its related symptoms., Aim of Study: The main aim of this study was to evaluate the antiplasmodial and cytotoxic activity of P. capensis extracts and chromatographic fractions. Spectroscopy analysis was conducted using 1 H NMR and GC-MS to tentatively identify the major classes of compounds and phytoconstituents that can be attributed to the observed antiplasmodial bioactivity., Materials and Methods: Pappea capensis twigs were dried and then ground to fine powder. A solvent mixture of dichloromethane: methanol: water (1:0.5:0.5, v/v) was used to extract. The polar extract was separated from the non-polar. The organic extract was dried to yield a DCM (I = 60 g) extract. The methanol in the aqueous extract was evaporated using a rotary vapour and the remaining water freeze dried to yield a water extract (II = 287 g). Extract I was further partitioned using a solvent mixture of DCM: MeOH (1:1, v/v), separated and concentrated under vacuum to yield dichloromethane (III = 40 g) and methanol (IV = 15 g) extracts. A water-based decoction (V = 10 g) was also prepared to establish the clinical relevance of the preparation administered by Vha-Venda people in South Africa. Extracts II, III and IV were further subjected to silica column chromatography, eluting with a series of different solvents with increasing polarity to yield a total of 25 fractions (A - Y). In vitro antiplasmodial tests on Plasmodium falciparum (NF54) and cytotoxicity screens on mammalian L-6 rat skeletal myoblast cells were performed on all extracts and fractions. Selectivity indices (SI) were also computed for all tested extracts and fractions which were further subjected to 1 H NMR spectroscopy and GC-MS analysis for the identification of the major classes of compounds present in the extracts., Results: From the assayed extracts, only extract I (IC 50  = 2.93 μg/ml; SI = 14), III (IC 50  = 2.59 μg/ml; SI = 21) and IV (IC 50  = 3.56 μg/ml; SI = 13) demonstrated the best antiplasmodial activity and selectivity. Of all assayed fractions, only N (0.6 μg/ml; SI = 91), D (0.85 μg/ml; SI = 37) and E (0.91 μg/ml; SI = 30) depicted the best antiplasmodial activity and selectivity. The 1 H NMR analysis of the extracts and fractions identified the prominent class of constituents to be aliphatic based which was tentatively identified as terpenoids. When further GC-MS analysis was conducted, the presence of lupin-3-one, lupeol acetate, α-amyrin, and β-amyrin phytoconstituents were tentatively confirmed. These constituents are triterpenoids with established antiplasmodial activity which can be tentatively attributed to the bioactivity observed in P. capensis twigs., Conclusion: The study validates the ethnomedicinal use of P. capensis for malaria treatment. It demonstrated the potential of discovering novel antiplasmodial constituents that could serve as drug hits through dereplication approaches where known compounds with established antimalarial activity can be bypassed to focus on the unknown., Competing Interests: Declaration of competing interest Authors declare no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The purpose of the present study was to assay the in vitro and in vivo anthelmintic activity (AA) of Caesalpinia coriaria (Cc) mature fruits against the nematode Haemonchus contortus (Hc). The Hc infective larvae were used to assess the in vitro AA through larval mortality assay. The exposure of larvae to the different treatments was performed in 96-well microtitration plates. The treatments were as follows: hydroalcoholic extract (HA-E, at 25-100 mg/mL), aqueous fraction (Aq-F, at 12.5-50 mg/mL), organic fraction (EtOAc-F at 12.5-50 mg/mL), compounds (1, methyl gallate and 2, gallic acid at 1.25-10 mg/mL), positive control (ivermectin at 5 mg/mL) and two negative controls (distilled water and 4% methanol). After exposure, dead and live larvae were quantified and results were compared to their controls. The in vivo assay was carried out by a faecal egg count reduction test (FECRT); artificially infected goat kids (F1: Boer x Nubia) were treated with Cc ground dried fruits to assess the AA. The treatments were established as follows: G1-untreated goats (negative control), G2-goats dewormed with ivermectin (positive control), G3-goats fed with Cc mature fruits (10% of their diet). Results in both in vitro and in vivo assays were analysed using an ANOVA through random design, applying a general linear model and mixed models. The in vitro results showed an evident larvicidal effect of the HA-E, EtOAc-F from Cc, indicating that the compound responsible for the AA was gallic acid. The results of the in vivo study corroborated the anthelmintic properties of Cc, reaching 78.6% reduction in the elimination of Hc eggs per gram of faeces. This plant represents a potential natural anthelmintic for the control of haemonchosis in goats under grazing conditions. Future studies should standardise the Cc extract or dried fruits for use in the management of nematodiasis in goat herds., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Ethno-Pharmacological Relevance: Gymnosporia montana (Roth) Benth an herbaceous shrub used in Indian traditional medicine their leaves decoction was used as mouthwash to get relieve from toothache, hence it is also known as Dantakashta in Sanskrit language which means the plant used for tooth problems. Traditionally the leaves juice used to alleviate inflammation and in some parts of India like Saurashtra in Gujarat, leaves were chewed as a folklore cure for Jaundice and in Bhandra region Karnataka, leaves extract mixed with cow milk used for jaundice. Hepatoprotective activity for G. montana leaves was well reported however, its use for inflammation and toothache are still not studied to investigate active phytoconstituents responsible for anti-inflammatory activity., Aim of the Study: The present study aimed at bioactivity guided isolation of G. montana leaves extracts using inhibition of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukins (IL-1β and IL-6) in RAW 264.7 cells in vitro assay to yield bioactive phytoconstituents., Materials and Methods: The n-hexane, ethyl acetate and methanol extracts prepared from G. montana leaves were evaluated for cell viability using MTT assay. The effect of extracts to inhibit the pro-inflammatory mediators like NO, TNF-α, IL-1β and IL-6 in RAW 264.7 macrophages was measured by enzyme-linked immunosorbent assay (ELISA). The quantitative analysis of the isolated phytoconstituents was performed using quantitative Nuclear Magnetic Resonance (qNMR)., Results: The n-hexane, ethyl acetate, and methanol extracts of G. montana leaves exhibited cell viability in the range of 97.43-84.88% at 50 μg/mL concentration in RAW 264.7 macrophages. In-vitro evaluation of extracts showed that n-hexane extract was most effective in inhibiting NO, TNF-α, IL-1β and IL-6 inflammatory mediators at 50 μg/mL in lipopolysaccharides (LPS) stimulated RAW 264.7 cells. Further n-hexane extract, its fraction GMHA3 and β-amyrin exhibited significant anti-inflammatory activity at 100, 50 and 30 mg/kg per oral, respectively in carrageenan-induced rat paw edema. The quantitative analysis by qNMR revealed β-amyrin as a major compound in the n-hexane extract., Conclusions: In vitro and in vivo bioassay results suggested that G. montana n-hexane extract, its fraction GMHA3 and β-amyrin exhibits significant anti-inflammatory activity proves the traditional uses of G. montana leaves. The reported activity of β-amyrin for periodontitis provides evidence of profound the use of G. montana leaves for toothache and anti-inflammatory activity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Preparations derived from the plant Calotropis procera, have been used for medicinal purpose though the plant is known for its toxic effects. The aerial parts of the plant contain latex in plenty and have been found effective in treating disorders of gastrointestinal system and cancer., Aim of the Study: This study evaluated the efficacy of C. procera dried latex extract prepared in methanol (MeDL) against inflammation and oxidative stress in experimental model of colorectal carcinoma (CRC)., Materials and Methods: Two subcutaneous injections of chemical carcinogen, 1,2-dimethylhydrazine (DMH; 150 mg/kg) were given at an interval of one week to induce CRC in rats. The MeDL (50 and 150 mg/kg) and aspirin (60 mg/kg) were given daily and their effect was evaluated on markers of oxidative stress and inflammation after completion of 8 weeks following second injection of carcinogen. A comparison was made with normal and experimental control groups. The colon tissue levels of glutathione (GSH), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), nitrite and myeloperoxidase (MPO) were determined. Enzyme-linked immunosorbent assay was performed to determine the levels of prostaglandin E 2 (PGE 2 ) and tumor necrosis factor-alpha (TNF-α) and immunohistochemical analysis was performed for IL-1β., Results: Induction of cancerous changes in the colon resulted in altered oxidative homeostasis as evident from a reduction in GSH level and SOD activity and rise in TBARS level when compared with normal rats. Elevated levels of nitrite, MPO, TNF-α, PGE 2 and immunoreactivity of IL-1β were also observed in these rats. The levels of these markers were normalized when the rats were treated with MeDL or anti-inflammatory drug, aspirin., Conclusion: This study demonstrates that suppression of oxidative stress and inflammation contributes to the beneficial effect of MeDL in rat model of colon carcinogenesis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Bocconia arborea S. Watson (Papaveraceae) is known as "palo llora sangre" and is used in Mexican traditional medicine for the treatment of infections, it is also used as anxiolytic, analgesic, and antidiabetic, among others., Aim of the Study: to evaluate the antinociceptive and gastroprotective activities of extracts from B. arborea and dihydrosanguinarine (DHS) in murine models., Materials and Methods: Organic extracts [hexane (HEX), dichloromethane (DCM) and methanol (MeOH)] were obtained by maceration. DHS was isolated and purified from HEX and DCM by precipitation and chromatographic column, respectively. Organic extracts and DHS were evaluated to determine their antinociceptive effect using formalin test in murine model. Also, the ambulatory effect of the HEX and DHS was determined in Open field test. The possible mechanism of action of DHS was explored in the presence of naltrexone (NTX, 1 mg/kg, i.p.), and picrotoxin (PTX, 1 mg/kg, i.p.). Gastric damage as possible adverse effect or gastroprotection were also investigated. Whereas DHS acute toxicological study was done, and 100 mg/kg of DHS was examined by electroencephalographic (EEG) analysis to discard neurotoxic effects., Results: The B. arborea extracts significantly showed effects in both neurogenic and inflammatory phases of the formalin test, where the HEX extract reached the major antinociceptive effect. A significant and dose-response (10, 30, and 100 mg/kg) antinociceptive activity was observed with the HEX (ED 50  = 69 mg/kg) and DHS (ED 50  = 85 mg/kg) resembling the effect of the reference analgesic drug tramadol (30 mg/kg). The significant effect of DHS was inhibited in the presence of NTX and PTX. Neither the extracts or DHS produced sedative effects or gastric damage per se at antinociceptive doses. The EEG analysis demonstrated central depressant activity but not sedative or neurotoxic effects at the highest antinociceptive dosage tested, and LD 50 is higher than 2000 mg/kg., Conclusions: HEX, DCM, and MeOH extracts showed significant antinociceptive activity, and DHS was identified as one of bioactive compounds without producing sedative, neurotoxic or gastric damage effects, as possible adverse effects reported for analgesic drugs. A role of opioid and GABA A neurotransmission appears to be involved as mechanisms of action of DHS, suggesting its potential for pain therapy and reinforcing the traditional use of B. arborea., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Natural products with targeted bioactivity have gained major attention in the field of cancer research owing to emerging anti-cancer drug resistance and off target toxicities. Chloroxylon swietenia (Roxb.) DC is recognized as a folklore medicinal plant and has numerous therapeutic benefits in the folklore medicine system, however the anti-cancer potential of this plant and its mechanism of action is poorly understood., Aims: The aim of the study was to investigate the anti-breast cancer efficacy of C. swietenia leaves methanol extract (CSLME) against MCF-7 hormone dependent human breast cancer cell line with possible mechanism of action., Methods and Results: The anti-breast cancer activity of CSLME against MCF-7 cells was assessed by evaluating its efficacy toward cytotoxicity, cell migration, colony formation, DNA fragmentation, apoptosis, cytoskeleton, angiogenesis, cell cycle regulation, and animal toxicity. The preliminary screening of CSLME against MCF-7 cells revealed the cytotoxicity (IC 50 20 μg/ml), inhibited cell migration, colony formation, and angiogenesis. It was observed that CSLME induces apoptosis by nuclear fragmentation and disruption of cytoskeleton by actin derangement. The results of Annexin V-FITC assay and cell cycle analysis by flow cytometry clearly pointed out the sizable fraction of apoptotic cells, and arrested the cells at G2/M phase of cell cycle. The results of the immunoblotting experiments showed that CSLME activates intrinsic pathway of apoptosis with down regulation of anti-apoptotic marker like Bcl2, up regulation of pro-apoptotic markers like Bax & Bad, along with successful cleavage of Caspase-9 and PARP-1. Further, western blot analysis revealed the possible down regulation of NF-κB pathway by CSLME, which may be responsible for anti-cancer activity in MCF-7 cells. In vivo animal model studies using NOD-SCID mice demonstrated impressive anti-tumor activity with significant reduction in tumor volume of MCF-7 tumor xenograft. Of note, in-vivo acute oral toxicity study as per Organization for Economic Cooperation and Development 423 revealed the nontoxic nature of CSLME., Conclusion: The in vitro and in vivo findings clearly outline the potential of CSLME as inhibitor of growth and proliferation of MCF-7 cells. Mechanistically, CSLME seems to activate intrinsic pathway of apoptosis, arrest cell cycle, target actin cytoskeleton, inhibit growth, colony formation, migration, and angiogenesis, with down regulation of NF-κB pathway leading to cell death., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Cervical cancer remains one of the significant causes of mortality in women due to the limitations of current treatment strategies and their associated side effects. Investigation of alternative medicine, including phytomedicine, has shown effective anti-cancer potential with fewer side effects. Azadirachta indica (commonly known as neem) is known for its medicinal properties. The present study investigated the anti-cancer potential of methanolic neem stem bark extract (MNBE) against cervical cancer using HeLa, SiHa, and ME-180 cell lines., Methods: Cytotoxic effect of MNBE on cultured cell lines was evaluated by MTT and clonogenic assay. The growth-inhibiting effect of MNBE was further confirmed by performing cell cycle analysis and apoptosis assay using flow cytometry. The anti-migratory effect of MNBE was evaluated by using wound healing and Boyden chamber assay. Real-time PCR was used to determine the mRNA expression, and western blot and flow cytometry was used to determine the protein levels of growth and migration-related genes., Results: MNBE significantly suppressed the growth and survival of cervical cancer cells in a dose-dependent manner by inducing cell cycle arrest and apoptosis. In addition, the growth inhibitory effect of MNBE was specific to cervical cancer cells than normal cells. Cell cycle arrest was correlated to transcriptional downregulation of cyclin dependent kinase 1 (CDK1), cyclin A, and cyclin B. Additionally, MNBE treatment resulted in the upregulation of active caspase-3 protein and downregulation of prosurvival genes, Bcl2, and survivin at mRNA level and NFkB-p65 at the protein level. Furthermore, MNBE inhibited the migration of cervical cancer cells accompanied by modulation of migration-related genes, including zona occludens-1 (ZO-1), matrix metalloproteinase 2 (MMP2), focal adhesion kinase (FAK), N-cadherin, snail, and E-cadherin., Conclusion: In summary, the present study provides the first evidence of MNBE in restricting cervical cancer cell growth and migration, which warrants further investigation for developing novel anti-cancer drugs., (© 2022. The Author(s).)

Given the complexity of pathophysiological processes of brain tumors, ineffective therapies, and high mortality rate, new therapeutic options with less toxicity are necessary. Hyssopus officinalis (hyssop) is an aromatic plant with important biological activities. The aim of this study is to assess the anti-cancer effect of hyssop extract on damages of glioblastoma multiforme. In this study, total flavonoids, phenolic content, and quantification of phenolic compound of hyssop extracts were analyzed. In vitro antioxidant properties of hyssop extract were also examined. In addition, cell viability, apoptosis, and cell cycle were evaluated in C6 glioma cell culture. In vivo, the rats were divided randomly into four main groups: intact, control, vehicle, and treatment groups. 1 × 10 6 C6 rat glioma cells were implanted into the right caudate nucleus of the rat's brain. The treatment group received the methanol extract of hyssop (100 mg/kg) for 7 days. Evolution of locomotor activity, tumor volume, survival rate, activities of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), vascular endothelial growth factor (VEGF) expression, TUNEL-positive cells, p53 and p21 mRNA expression, and histological alterations were performed. The results showed that the methanol extract of hyssop increased the apoptosis and reduced the cell division of C6 glioma cells in cell culture. Moreover, methanol extract decreased the tumor volume and prolonged survival. Also, the activity of SOD and CAT enzymes was reduced in tumor tissue and enhanced in surrounding tissue. TUNEL-positive cells were increased in methanol extract of hyssop group. The expression of p53 and p21 mRNA was upregulated in the treatment group. Moreover, the histological analysis indicated a considerable decrease in invasion of tumor cells and inflammation in the hyssop-treated rats. According to the achieved results, it can be stated that hyssop has sufficient potential to inhibit damage of brain tumors, at least in part, by affecting the oxidative stress and cell proliferation pathways., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer in the world. It is the third leading cause of cancer-related mortality. In more than 80% of people liver cancer-related death is due to its poor prognosis. The flavonoids obtained from natural sources have potent therapeutic effects on HCC. The flavonoid rich methanolic fraction obtained from ethyl acetate extract of leaf of Cestrum nocturnum (MFLCN) was analyzed by UPLC-QTOFMS/MS for the presence of different flavonoids. The physiochemical and pharmacokinetics properties of the identified flavonoids were performed by absorption, distribution, metabolism, excretion, and toxicity (ADMET). It was selected on the basis of Lipinski rule and hepatotoxicity evaluations. The potential gene dataset of HCC were taken from gene card database and targets compounds were selected from target net prediction. Gene ontology and pathway enrichment analysis of HCC was performed via enricher and David web tools. Cytoscape was used to visualize targets and network pathways. MFLCN contains 33 flavonoids. Among these flavonoids, apigenin was selected as principal active compound on the basis of their pharmacokinetic and ADMET properties. Apigenin has 92 targets out of 627 total targets related to HCC, while there was13 pathways in the target-pathway network. Results revealed that apigenin regulates cell proliferation and survival, primarily through different signaling pathways like estrogen, VEGF, PI3K/AKT1, TNF, FoXO, and Ras signaling pathways. Thus, integrating network pharmacology prediction with m-RNA and human protein atlas validation could be an effective method for understanding the molecular mechanism of apigenin on HCC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Saussurea heteromalla is the one of specie of Saussurea plant belonging to family Asteraceae. The Saussurea heteromalla found extensively in Pakistan. The literature review highlights numerous biological aspects of Saussurea heteromalla. This research therefore aims to assess its potential anti-inflammatory, antioxidant, anti-cancer. Carrageenan induced rat paw edema model was used for the evaluation of anti-inflammatory activity. DPPH method was used to evaluate anti-oxidant activity. The MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide) test was used to assess the viability of the cells for the assessment of the cytotoxic effect of the extract. Methanolic Saussurea heteromalla flowers extract analysis carried by GC-MS, result 19 different peaks. The methanolic extract of Saussurea heteromalla at 400mg/kg dose have equal anti-inflammatory action when compare with standard that is diclofenac sodium. Anti-oxidant activity of methanolic extract is also very good. IC 50 value of methanol extract was 25µg/ml. 18.72% cell survive out of 100 when methanolic flower extract of Saussurea heteromalla was given at the dose of 400mg, which shows the cytotoxic effect. This activity shows that plant Saussurea heteromalla methanolic flowers extract have anti-inflammatory, anti-oxidant, cytotoxic effect. The isolation and characterization-based investigations proclaiming the biologically leading active molecule are worthy for further study in this regard.

Ripe figs, barks, and wood of Ficus vallis-choudae are used in traditional medicine against several conditions including nausea and malaria. However, its use is still to be scientifically documented and validated. Hence, the aim of the present work was to evaluate the antiplasmodial activity of the dichloromethane-methanol (DCM-MeOH (1:1)) crude extract, their hexane, dichloromethane, ethyl acetate, and methanoli fractions, as well as the isolated chemical constituents. The chemical study of the DCM-MeOH (1:1) crude extract of F. vallis-choudae figs led to the isolation of fifteen (15) known compounds identified based on their spectroscopic data [one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), mass spectrometry] and by comparison of these data with those reported in the literature. Some of the isolated compounds were assessed in vitro for their antiplasmodial activity against Plasmodium falciparum chloroquine-sensitive 3D7 (Pf3D7) and multidrug-resistant Dd2 strains. The dichloromethane fraction exhibited very good antiplasmodial activity against both strains with IC 50 values of 13.86 μg/mL and 8.18 μg/mL, respectively. Among the tested compounds, wighteone (2) was the most active against P. falciparum 3D7 (IC 50  = 24.6 ± 1.5 μM) and Dd2 (IC 50  = 11.9 ± 2.4 μM) strains. The obtained results could justify the traditional uses of F. vallis-choudae against malaria. Wighteone appears to be the most active ingredient. However, further consideration of this compound as starting point for antimalarial drug discovery will depend upon its selectivity of action towards Plasmodium parasites. HIGHLIGHTS: • 15 (fifteen) compounds were isolated from the dichloromethane-methanol extract of Ficus vallis-choudae. • Their structures were determined on the basis of their spectroscopic data. • The dichloromethane fraction showed promising activities on the Pf3D7 and PfDd2 strains with IC 50 values of 13.86 and 8.18 µg/mL, respectively. • Wighteone was the most active compound against PfDd2 (IC 50  = 11.9 ± 2.4 μM)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This experimental study determined the in vitro , in vivo , and toxicity effects of Cinnamomum zeylanicum methanolic extract (CZME) against Toxoplasma gondii infection., Methods: The in vitro activity of CZME T. gondii tachyzoites was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Infected mice were treated with CZME for two weeks at doses of 20, 40, and 60 mg/kg/day. Then, the therapeutic effects of CZME were evaluated by assessing the mean number and mean size of T. gondii tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, and mRNA expression levels of bradyzoite surface antigen 1 (BAG1) by real-time PCR., Results: CZME significantly (p <0.001) increased the mortality rate of parasites in a dose- and time-dependent response. The mean number of intracellular tachyzoites was significantly reduced after CZME therapy. The treatment of infected mice with CZME resulted in a significant (p <0.001) downregulation of BAG1 and the level of lipid peroxidation (LPO) and nitric oxide (NO) as oxidative stress markers. However, a considerable rise (p <0.05) was found in the levels of antioxidant markers such as glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD). In a dose-dependent response, after treatment of infected mice with CZME, the level of pro-inflammatory cytokines of IFN-γ, IL-1β, and IL-12 was considerably elevated. CZME had no significant cytotoxicity on Vero cells, with a 50% cytotoxic concentration of 169.5 ± 5.66 μg/ml., Conclusion: The findings confirmed the promising therapeutic effects of CZME on chronic toxoplasmosis in mice. Nevertheless, further investigations must confirm these results, elucidate its precise mechanisms, and examine its effectiveness in human volunteers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alanazi and Almohammed.)

Cryptosporidiosis causes diarrhea in both immunocompetent and immunocompromised individuals, with acute manifestations occurring particularly in children and the elderly. Up till now, there is no curative therapy for cryptosporidiosis, so discovery of new classes of drugs are of great importance. This study aimed to examine the effect of methanol leaves extracts of the three Podocarpus species; P. macrophyllus (Thunb.), P. gracilior (Pilg.) and P. elongatus (Aiton) L' Hér. ex Pers and their combination on Cryptosporidium parvum (C. parvum) in experimentally infected mice in comparison with the commercially used drug, Nitazoxanide. As well as spectrophotometric estimation of the total phenolic and flavonoid content of these extracts was done. Results revealed that treatment with these three Podocarpus extracts and their combination showed a significant reduction of the number of C. parvum oocyst shed in the stool of infected mice compared to infected control group and Nitazoxanide- infected treated group at P < 0.001. The combination of the three Podocarpus extracts was the most effective treatment showing the lowest number of oocysts shedding in comparison with other used extracts and Nitazoxanide. Histopathological inspection of sections from ilium and colon displayed signs of improvement after treatment with P. macrophyllus and P. gracilior extracts and more remarkable improvement when the three extracts were combined. It was concluded that the three Podocarpus species extracts used in this study had a promising anti-Cryptosporidium activity especially when they were combined.

Alternative and natural therapies are needed for malignant melanoma (MM), the most deadly skin cancer type due to chemotherapy's limited effect. In the present study, we evaluated the anticancer potentials of Inula viscosa methanol and water extracts (IVM and IVW) on MM cells, A2058 and MeWo, and normal fibroblasts. After the chromatographic and antioxidant activity analysis, their antiproliferative effects were determined with the increasing doses for 24-72 h. IVM induced more cell death in a dose and time-dependent manner in MM cells compared to IVW. This effect was probably due to the higher amount of phenolics in it. IVM significantly induced more apoptotic death in MM cells than fibroblasts ( p  < 0.01), which was also supported morphologically. IVM also caused cell cycle arrest at G0/G1 and G2/M phases in A2058 and MeWo, respectively, and suppressed the migration ability of MM cells ( p  < 0.01). Additionally, IVM was found to have significant potential in regulating MM-related miRNAs, upregulating miR-579 and miR-524, and downregulating miR-191 and miR-193, in MM cells ( p  < 0.05, p  < 0.01). As a result, the anticancer effect of IVM via regulating miRNAs' expression has been demonstrated for the first time. Thus, IVM, with these potentials, may be a promising candidate for MM treatment.

Irritable bowel syndrome (IBS) is a world-wide disease prevalently in Western nations. It influences about 15% of the western populace, with a negative effect on the quality of life and furthermore on medical services costs. Anticholinergic antispasmodics are first line of treatment for discomfort or abdominal pain, particularly if unrelieved after alleviation of stoppage or antidiarrheal treatment. Otilonium bromide (OTB) is quaternary ammonium compound with action on distal GI tract as antispasmodic. It is utilized in the treatment of patients influenced by Irritable inside disorder (IBS) because of its particular pharmacokinetic and pharmacodynamic properties. OTB is poorly absorbed systematically was viable in contrast with different medications used for same purpose, for example, pinaverium bromide and mebeverine, with a good tolerability profile. The effects are long lasting, even after stopping the dosage regime for reduction of abdominal pain. In this review, an overview of mechanism of action, pharmacologic action, synthesis and particularly various analytical and bioanalytical methods are discussed. The analytical methods discussed are spectrophotometry including Near Infrared Spectroscopy (NIRS), chromatography and capillary electrophoresis methods are described with the range, limit of detection and quantification. The paper also provides details of scope of further extension of analytical methods. It was found that most of the analytical methods involves usage of toxic solvents e.g., methanol, acetonitrile, chloroform etc. posing risk to the analyst as well as environment.

Origanum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose ∼5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G 0 /G 1 , S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML.

Haemonchosis is a gastrointestinal parasitic disease of economic importance in ruminants especially sheep and goats. In view of the rising costs of conventional veterinary anthelmintics and the development of resistance by Haemonchus contortus, there is a need to develop alternative ethnoveterinary therapies for the treatment and management of Haemonchosis. This study investigated the anthelmintic activity of Dennettia tripetala G. Baker (Annonaceae) fruits against Haemonchus contortus in red Sokoto goats. The maximum tolerated dose was determined in adult albino rats administered, 3000, 4000, and 5000 mg/kg body weight of the crude methanol extract (CME) fraction, and observed over a period of 48 h for signs of toxicity and mortality. The in vivo anthelmintic activity was evaluated using 20 kids infected with H. contortus and randomly allocated into 5 groups (1, 2, 3, 4, and 5). Kids in groups 1, 2, and 3 were treated with CME at doses of 1250, 2500, and 5000 mg/kg respectively for 3 consecutive days per os. Groups 4 and 5 were treated with albendazole (7.5 mg/kg) once and distilled water (5 ml) respectively and served as treated and untreated controls. Blood samples were collected for haematology. The maximum tolerated dose of the CME of D. tripetala did not produce observable signs of toxicity or death in all the rats given up to 5000 mg/kg. There was significant (P < 0.05) reduction in faecal egg count by CME at doses of 1250 mg/kg (91.6%), 2500 mg/kg (98.5%), and 5000 mg/kg (100%) at day 14 post-treatment. The total plasma protein (TPP) and FAMACHA © scoring values were significantly improved (P < 0.05) in the treated groups. These results indicate that methanol extract and fractions of D. tripetala fruits possess beneficial anthelmintic activity against H. contortus and may be a suitable alternative anthelmintic candidate for the control of haemonchosis in goats., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The pathological process of traumatic spinal cord injury (SCI) involves excessive activation of microglia leading to the overproduction of proinflammatory cytokines and causing neuronal injury. Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays an important role in mediating inflammation, cell proliferation, survival, and immunity., Methods: We aim to investigate the mechanism and pathway of the Sphk1-mediated neuroinflammatory response in a rodent model of SCI. Sixty Sprague-Dawley rats were randomly assigned to sham surgery, SCI, or PF543 (a specific Sphk1 inhibitor) groups. Functional outcomes included blinded hindlimb locomotor rating and inclined plane test., Results: We discovered that Sphk1 is upregulated in injured spinal cord tissue of rats after SCI and is associated with production of S1P and subsequent NF-κB p65 activation. PF543 attenuated p65 activation, reduced inflammatory response, and relieved neuronal damage, leading to improved functional recovery. Western blot analysis confirmed that expression of S1P receptor 3 (S1PR3) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) are activated in microglia of SCI rats and mitigated by PF543. In vitro, we demonstrated that Bay11-7085 suppressed NF-κB p65 and inhibited amplification of the inflammation cascade by S1P, reducing the release of proinflammatory TNF-α. We further confirmed that phosphorylation of p38 MAPK and activation of NF-κB p65 is inhibited by PF543 and CAY10444. p38 MAPK phosphorylation and NF-κB p65 activation were enhanced by exogenous S1P and inhibited by the specific inhibitor SB204580, ultimately indicating that the S1P/S1PR3/p38 MAPK pathway contributes to the NF-κB p65 inflammatory response., Conclusion: Our results demonstrate a critical role of Sphk1 in the post-traumatic SCI inflammatory cascade and present the Sphk1/S1P/S1PR3 axis as a potential target for therapeutic intervention to control neuroinflammation, relieve neuronal damage, and improve functional outcomes in SCI.

Objectives: Several cultivars of Allium cepa L. have been studied for anti-inflammatory and analgesic activities but there is inadequate information on such biological activities of the concentrated extracts of the Nigerian grown red cultivar A. cepa bulb., Methods: The anti-inflammatory models used in this study were Carrageenan-induced paw oedema and formalin-induced paw lick in rats, while acetic acid-induced abdominal writhing, hot plate reaction, hot water tail flick tests in mice were the analgesic models., Results: At 30 min post-induction (pi), the inhibition of paw oedema (62.50%) by 200 mg/kg of methanol extract of red cultivar A. cepa bulb (MERCACB) was significantly (p<0.001) higher than that of indomethacin (15.63%) at 10 mg/kg. The paw oedema inhibition at 60 min pi by MERCACB (76.92%) was significantly higher than that of indomethacin (41.03%). At the early phase of formalin paw-lick test, the pain reaction time (PRT) of rat treated with MERCACB (400 mg/kg) was significantly lower than that of indomethacin and the control groups. The hotplate test revealed that PRT of mice treated with 800 mg/kg of MERCACB were significantly (p<0.01) longer in comparism to indomethacin and control groups. The PRT of mice subjected to thermal pain due to hot water and treated with 800 mg/kg of MERCACB was significantly (p<0.05) longer than that of the control group., Conclusions: These findings indicate that MERCACB possesses potent anti-inflammatory and analgesic properties which confirm the traditional use of the plant for the treatment of inflammatory diseases and may be useful as a future therapeutic agent., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Modern research propounded that alteration in signaling pathways have shown strong connection with the progression of cervical cancer and modulation of these pathways by natural compounds could be a better treatment approach for the management of cervical cancer. Additionally, inhibitory role of methanolic extract of Moringa oleifera leaves against Jab1 has not been elucidated yet. Therefore, we have elucidated the inhibitory potential of MMLE against Jab1 in cervical cancer by analyzing several In Vitro assays. The MMLE treatment in cervical cancer cells showed decreased cell growth in a dose and time dependent manner. Furthermore, MMLE treated cervical cells have also depicted enhanced nuclear condensation (apoptotic induction potential) confirmed by Hoechst analysis. RT-PCR results clearly illustrated the inhibitory potential of MMLE against Jab1 via down regulating its expression. Conversely, a significant increase in p27 expression was also reported which could explain the cells growth arrest at G0/G1 phase. Additionally, enhanced ROS production and caspase-3 activation explains one of the possible mechanisms behind the inhibitory potential of MMLE against Jab1 in cervical cancer cells (HeLa). Thus our experimental findings may pave a potent phyto compound for targeting a crucial signalosome (Jab1) in cervical cancer.

Objective: The present study aimed to evaluate the efficacy of methanolic extract of Muntingia calabura L. leaves (MEMC) in ameliorating oxidative stress and inflammation associated with 1,2-dimethyl hydrazine (DMH) induced colon cancer., Methods: The antioxidant enzymes, oxidative stress markers, liver and renal toxicity markers were evaluated. Histopathological examination of colon tissues was carried out with the aid of alcian blue stain and Hematoxylin and Eosin stain., Results: MEMC supplementation at doses of 100 and 200 mg/kg body weight of rats causes the antioxidant enzymic levels to retain near to its normal range. Meanwhile the oxidative stress markers, which showed an elevation from its normal level upon DMH administration, gets significantly reduced on MEMC treatment. Histopathological observation also revealed that the severity of colorectal cancer was reduced by the supplementation of MEMC., Conclusion: The findings from the present study showed that MEMC can exert a potential role to ameliorate the oxidative stress and inflammation associated with colorectal cancer.

Non-small cell lung cancer (NSCLC) constitutes nearly 85% of all cases of lung cancer. Drug resistance, dose-limiting toxicity, and metastasis in NSCLC eventually reduce the efficacy of chemotherapeutics. In this study, we have shown that the methanol-ethyl acetate partitioned fraction from Magnolia grandiflora L. seeds (MEM) exhibit potential anti-cancer activities against NSCLC H1975 cells in vivo and in vitro. MEM significantly inhibited the proliferation of H1975 cells in a concentration- and time-dependent manner. Further, MEM exhibited potent anti-tumor efficacy and low toxicity in nude mice bearing H1975 tumors. Our study also showed that MEM could induce cellular apoptosis in H1975 cells by down-regulating the protein expression levels of Akt and p-Akt-473, and by increasing the ratio of Bax/Bcl-2. Also, MEM significantly inhibited metastasis-related cell invasion and migration of H1975 cells, which associated with the down-regulation of HIF-1α, MMP-2, and MMP-9 protein expression levels. Thus, our data shows that MEM may be an effective fraction of M. grandiflora in NSCLC treatment.

In our previous study, we found that the methanolic extract of Sanoshashinto () (SHXXTM) exhibited significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine were the main antihypertensive constituents in SHXXTM. We also speculated that the baicalin-berberine (BB) combination produced vasorelaxant effects by activating the NO/cGMP pathway, and the BK Ca channel and the DAG/PKC/CPI-17 pathway were involved. In this study, we examined the vasorelaxant effects using helical strips of rat aorta pretreated with different activators or inhibitors. The results suggested that the K ATP channel and the voltage-dependent Ca 2+ channel (VDCC) were also involved in the vasorelaxant effects. Furthermore, we found that SHXXTM and the BB combination reduced left ventricular hypertrophy and altered gut microbiota. Together, the results indicated that Sanoshashinto might have comprehensive effects on ameliorating hypertension.

Objective: To determine the potential effect of Pyrenancantha staudtii extract on experimentally induced seizures in mice and to evaluate the role of benzodiazepines, naloxone, and serotonin within these pathways., Methods: Animal behaviours were evaluated using open field, hexobarbitone-induced sleep model, and anticonvulsant activity using picrotoxin-, or strychnine-, or isoniazid-induced convulsions. Attempt to understand the mode of action of the anticonvulsant activity of the plant, three notable antagonists (flumazenil, 3 mg/kg; naloxone 5 mg/kg, i.p., and cyproheptadine, 4 mg/kg, i.p) were used., Results: The results revealed a significant (p < 0.05) reduction in the frequency of rearing and grooming episodes compared with the control. The extract of P. staudtii potentiates the sleeping time of hexobarbitone-induced hypnosis in a dose-related manner. P. staudtii stem bark extracts significantly (p<0.05) prolonged the onset of a seizure and attenuated the duration of seizure in a dose-dependent manner in picrotoxin- and or isoniazid-induced seizures. While, P. staudtii stem bark extract at all doses (100, 200, and 400 mg kg-1) though significantly prolonged the onset of action, but did not confer any significant changes on the duration, as well as mortality in this strychnine-induced seizure model. However, the anticonvulsant activity of the methanolic extract of P. staudtii was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist) and naloxone (opioid receptor antagonist) but not cyproheptadine (5-HT2 receptor antagonist) in picrotoxin-induced convulsion., Conclusion: The data obtained suggest that methanol extract of P. staudtii possessed significant anticonvulsant effect, thereby confirming the traditional uses of P. staudtii in the treatment of epilepsy; mechanisms of which could involve the interaction with GABAergic and or opioidergic system., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, which often affects colon or rectum or both. It is now well recognized that sphingosine kinases-1/sphingosine-1-phosphate (S1P) signaling may have a very significant potential as targets for therapeutic intervention in UC. Compared with the pure dextran sodium sulfate group, administration of PF543 significantly reduced clinical symptoms with less weight loss, diarrhea, and shortening of the colon. The severity of colitis was improved with reduced disease activity index and degree of histological damage in colon. Moreover, treatment with PF543 not only decreased S1P but also inhibited mRNA expression of proinflammatory factors such as interleukin (IL)-1β and IL-6. This suggests that PF543 might exhibit an anti-inflammatory function against colitis through inhibition of expression of proinflammatory factors.

Calotropis procera, a latex producing plant is known to possess medicinal properties including its beneficial effect in gastrointestinal disorders. The anti-inflammatory effect of its latex in various experimental models is noteworthy and in light of this the present study was carried out with an objective to evaluate its efficacy in ulcerative colitis, an inflammatory condition of the colon. Colitis was induced in rats by acetic acid and the rats were divided into four groups where one group served as experimental control and the other groups were treated with two doses of methanol extract of dried latex of C. procera (MeDL; 50 and 150 mg/kg) and mesalazine (MSZ; 300 mg/kg). The study also included normal control (NC) group for comparison of various parameters related to colon like macroscopic changes, ulcer score, adherent mucus content, weight/length ratio, small intestinal transit, oxidative stress and inflammatory markers, tissue histology and immunoreactivity of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa beta (NFκB) subunit p65. Treatment of colitic rats with MeDL produced a significant reduction in colonic mucosal damage as revealed by macroscopic and microscopic evaluation and normalization of tissue levels of oxidative stress markers and pro-inflammatory mediators. The protection afforded by MeDL was also evident from its restorative effect on tissue histology and expression of COX-2, iNOS and NFκB(p65). This study shows that by targeting oxidative stress and NFκB(p65) mediated pro-inflammatory signaling, the latex of C. procera affords protection in colitis and its effect was comparable to that of mesalazine. This study suggests that latex of C. procera could serve as a promising therapeutic option for treating inflammatory conditions of the colon., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Roots, bark, stem/twigs, and leaves of Fraxinus xanthoxyloides are being used regionally for the cure of malaria, jaundice, internal injuries, pneumonia, pain, rheumatism and also in fracture of bones. Our objective was to assess the methanolic leaves extract of F. xanthoxyloides for its antioxidant capability against oxidative stress induced by carbon tetrachloride (CCl 4 ) in the kidney of Sprague-Dawley rats. Duration of this experiment was 30 days and doses were given on alternative days. Urine of rats was assessed for kidney function and renal tissues for antioxidant enzymes activity, biochemical markers, comet assay and histopathology. Enhanced urinary creatinine, urobilinogen levels and decreased creatinine clearance, protein contents, and albumin levels were observed by CCl 4 administration when matched to controls. CCl 4 injection also decreased the level of reduced glutathione, catalase, super oxide dismutase, peroxidase, glutathione s-transferase, glutathione reductase, and tissue protein while elevated the levels of thiobarbituric acid reactive substances, DNA damages and H 2 O 2 in renal tissues of experimental animals. Co-treatment of FXM and silymarin, lead to the restoration of all the above tested parameters of kidney. Through this study we affirmed the ameliorating role of F. xanthoxyloides in oxidative stress affiliated disorders of kidney.

According to the Brazilian folk medicine, the leaves of Plinia edulis (Vell.) Sobral (Myrtaceae), known as cambuca, are indicated in the treatment of gastric disorders. Infusions of P. edulis leaves were previously demonstrated to contain both maslinic (MA) and ursolic acids (UA). Both triterpenes have also been identified in the methanolic extract of peels from P. edulis fruit (MEPPE); however, the antiulcer effects of MEPPE have not yet been studied. This study therefore evaluates the gastroprotective potential of MEPPE, MA, and UA using ethanol/HCl- and indomethacin-induced gastric ulcers in mice. In addition, the in vitro effects of these compounds on the H + , K + -ATPase activity and on the free radical DPPH were measured. When used at concentration of 100 μg/mL, both MEPPE and UA were found to reduce the DPPH radical levels by 78.66 and 60.14%, respectively. However, MA did not reduce DPPH radical levels. Our results illustrated the antiulcer effects of MEPPE, MA, and UA against experimental ulcer models when administered by either the oral or the intraperitoneal routes. In addition, MEPPE reduced the size of ethanol/HCl-induced ulcers in a dose-dependent manner (log half-maximal effective oral dose, LogED 50  = 1.09). Interestingly, UA promoted gastroprotection at lower doses than MA by increasing the production of mucin levels at 692%; however, it does not alter the activity of H + , K + -ATPase. In contrast, both MEPPE and MA, when incubated at concentrations of 10 and 100 μg/mL, inhibited H + , K + -ATPase activity in 61.81, 68.37, 54.04, and 70.45%, respectively. These results confirm that MEPPE, MA, and UA display gastroprotective activity through different modes of action; MA inhibits H + , K + -ATPase activity, whereas UA favour the mucus barrier.

Context: Leaves of Muntingia calabura (Elaeocarpaceae) are widely used in traditional medical practice; scientific findings show various pharmacological activities. However, its anticancer effect has not been investigated thoroughly yet., Objective: The objective of this study is to study the chemoprevention effects of MEMC L against azoxymethane (AOM)-induced colon cancer and to examine the involvement of endogenous antioxidants Materials and methods: Male Sprague-Dawley rats, divided into five groups (n = 7), were injected intraperitoneally once weekly for 2 weeks with 15 mg/kg AOM, except for the normal group (received saline). The animals were then administered orally for 8 weeks with 8% Tween-80 (vehicle; normal group), 8% Tween-80 (vehicle; cancer group) or, 50, 250 or 500 mg/kg MEMC. After treatments, colon samples were collected from each rat for the histopathological analysis, quantification of aberrant crypt foci formed and determination of colon antioxidant levels. MEMC was also subjected to HPLC analysis., Results: The extract exerted significant (p < 0.05): (i) anti-carcinogenesis activity, indicated by a decrease in the total aberrant crypt formation; (ii) antioxidant activity by increasing the colon tissue antioxidant markers [i.e., superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH)] and reducing the oxidant marker (i.e., malonaldehyde (MDA) levels in comparison with the cancer group. HPLC analysis demonstrated the presence of rutin., Discussion and Conclusions: Muntingia calabura leaves exert anticancer effect against AOM-induced colon cancer possibly via the action of flavonoids on the colon tissue antioxidant activity.

Objective: To investigate potential reproductive effects of Pterocarpus marsupium methanolic extract on testosterone propionate induced Polycystic Ovarian Syndrome (PCOS) in female albino rats., Methodology: PCOS was induced in female albino rats by daily injecting testosterone propionate for 15 days intraperitoneally. Animals are divided into five groups with six rats per group. Group 1: Control group received olive oil, Group 2: Testosterone propionate+natural recovery, Group 3: Testosterone propionate + a dose of clomiphene citrate (standard), Group 4 and 5: Testosterone propionate + low dose (200mg/kg) and high dose (400mg/kg) b.w respectively for 15 days. Various biochemical and histopathological investigations were assessed., Results: Methanol extract of Pterocarpus marsupium was able to exert its protective effect successfully by restoring all the parameters to normal and diminishing the cysts found in ovaries., Conclusion: Pterocarpus marsupium showed potential reproductive effects on testosterone propionate induced PCOS female albino rats and could be used as an alternative therapy in the treatment of PCOS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of death worldwide. Since there is a dire need for novel and effective therapies to improve the poor survival rates of advanced pancreatic cancer patients, we analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on pancreatic cancer cell lines in vitro and in vivo. OSU-A9 exhibited a stronger antitumor effect than gemcitabine on two pancreatic cancer cell lines, including gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down-regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and decreased phosphorylation of JAK and STAT3. Cell migration and invasiveness assays showed that OSU-A9 reduced cancer cell aggressiveness and inhibited BxPC-3 xenograft growth in nude mice. These results suggest that OSU-A9 modulates the p38-JAK-STAT3 signaling module, thereby inducing cytotoxicity in pancreatic cancer cells. Continued evaluation of OSU-A9 as a potential therapeutic agent for pancreatic cancer thus appears warrented.

Ethnopharmacological Relevance: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies reported that the active component tanshinones displayed a variety of biological activities: anti-thrombous, anti-allergic, anti-inflammatory, antioxidant and anti-tumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated. The aim of this study was to investigate the effects of CTN on the growth inhibition, apoptosis and molecular targets of human non-small cell lung cancer (NSCLC)., Materials and Methods: CTN-induced cytotoxicity was determined by MTT assay. The cell survival was evaluated using clonogenic survival assay. The morphology of Glc-82 cells after treatment with CTN was determined by fluorescence microscopy. Cell cycle distribution was revealed by flow cytometry. The apoptotic cells were quantified with annexin V-FITC/PI staining and flow cytometry, and observed using Hoechst 33258 staining and TUNEL assays. The expression levels of proteins were analyzed using western blot. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice., Results: CTN inhibited the proliferation of NSCLC in a dose-dependent manner and induced both early and late apoptosis. Treatment of Glc-82 cells with CTN (5-80μg/ml) significantly (p<0.05) suppressed the cell proliferation in a concentration and time-dependent manner. CTN induced significant (p<0.05) and dose-dependent apoptosis of Glc-82 cells. Cell cycle assay showed that CTN induced a G 2 /M phase arrest, and significantly (p<0.05) increased expression of p53 and p21, actived caspase-3/9 and PARP1, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, CTN decreased expression of the anti-apoptotic protein Bcl-2, Bcl-xl and increased expression of the pro-apoptotic protein Bax. Result also showed that CTN could increase expression levels of PTEN, and reduce the phosphorylated levels of Akt (protein kinase B) on Thr 308 and Ser 473 domain. In vivo assay showed that the antitumor effect of CTN was significantly augmented without increasing toxicity in nude mice bearing Glc-82 xenograft., Conclusion: The PTEN/Akt signaling axis is defined as a critical pathway regulated by PTEN in NSCLC. CTN, the methanol extract of Salvia miltiorrhiza Bunge, are the active compounds as shown by their ability to induce apoptosis through the mitochondrial pathway of apoptosis and PTEN-mediated inhibition of PI3K/Akt pathway. CTN could inhibit tumor growth more efficiently, which supports the ethno-medicinal use of this herb as an alternative or complementary therapy for NSCLC., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)