Search

The current review discuss the chemistry, nutritional composition, toxicity, and biological functions of garlic and its bioactive compounds against various types of cancers via different anticancer mechanisms. Several scientific documents were found in reliable literature and searched in databases viz Science Direct, PubMed, Web of Science, Scopus, and Research Gate were carried out using keywords such as “garlic”, “garlic bioactive compounds”, “anticancer mechanisms of garlic”, “nutritional composition of garlic”, and others. Garlic contains several phytoconstituents with activities against cancer, and compounds such as diallyl trisulfide (DATS), allicin, and diallyl disulfide (DADS), diallyl sulfide (DAS), and allyl mercaptan (AM). The influence of numerous garlic- derived products, phytochemicals, and nanoformulations on the liver, oral, prostate, breast, gastric, colorectal, skin, and pancreatic cancers has been studied. Based on our search, the bioactive molecules in garlic were found to inhibit the various phases of cancer. Moreover, the compounds in this plant also abrogate the peroxidation of lipids, activity of nitric oxide synthase, epidermal growth factor (EGF) receptor, nuclear factor-kappa B (NF-κB), protein kinase C, and regulate cell cycle and survival signaling cascades. Hence, garlic and its bioactive molecules exhibit the aforementioned mechanistic actions, and thus, they could be used to inhibit the induction, development, and progression of cancer. The review describes the nutritional composition of garlic, its bioactive molecules, and nanoformulations against various types of cancers, as well as the potential for developing these agents as antitumor drugs.

To prospect an isozyme-specific, effective inhibitor against the physiologically-crucial enzyme phosphodiesterase 1 (PDE1), phytochemicals from Pistacia integerrima galls were screened. The chloroform fraction of gall extract was subjected to column chromatographic which led to the isolation of compound 1, elucidated to be 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (a flavone). In vitro and in silico PDE1 inhibitory activity of the compound 1 was investigated. EDTA, a known PDE1 inhibitor, was used as the reference. The flavone exhibited in vitro attenuation towards snake venom PDE1. IC50 response was superior to the standard chelator. An in silico molecular docking study was carried out using 3D structure of PDE1 to study the binding interactions of compound 1. The docking study predicted that flavone had a lower binding affinity (-7.6 kcal/mol) and total energy (-95 kcal/mol) score compared to EDTA. The minimal energy associated with the ligand-protein complex implied that isolated compound 1 can serve as a therapeutic agent against PDE1 enzyme-provoked ailments like asthma, hypertension, schizophrenia, and erectile dysfunction.

Presently, the majority of breast tumors are estrogen receptor (ER) positive. Breast cancer (BC) is defined by uncontrolled cell proliferation (CP) in breast tissue. BCs are caused by the overexpression of genes that promote CP in breast cells. The discovery of effective inhibitors is an excellent chemopreventive method. Our in silico approach analysis offers a pharmacoinformatics methodology for identifying lead molecules targeting cochaperone HSP90 and the epidermal growth factor receptors (EGFR) and human epidermal growth factor receptor 2 (HER2)/neu receptor. BC has been associated with the high expression of these targets. The use of drug-likeness filters aided in determining the therapeutic properties of possible lead compounds. In this study, docking-based virtual screening (VS) was performed. Database of about 450 cancer marine compounds was used. The X-ray-assisted structure of ERα with 4-OHT (PDB code: 3ERT) was chosen for 4-OHT. A docking-based virtual screening was performed on the dataset supplied using the molecular operating environment (MOE) dock application. The binding energy (BE) and explanation of the protein inhibitor interaction (PII) are crucial findings for future both in terms of dry or wet lab research. The GBVI/WAS binding-free energy assessment (in kcal/mol) scores were used to grade the compounds. Compounds with a BE of less than -9.500 kcal/mol were deemed to be the most effective inhibitors. For further analysis, the top seven structurally diverse scaffolds were selected. Seven marine compounds exhibited the best docking score, which validates them to be potent anti-BC compounds. These compounds’ bioactive potential and prospective drug-likeness profile make them promising leads for further experimental research.

Urease is a metallo-protein in which two nickel (Ni) atoms are present at the active site. It is found in all the organisms such as, bacteria, fungi, plants, and in algae. Urease enzymes are also involved in catalyzing the hydrolysis of urea into CO2 and NH3. Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. Current research work aimed to purify the three di-naphthodiospyrols namely; 5,4 -dihydroxy-1-methoxy-6,6 -dimethyl7,3-binaphthyl-1,4,5,8-tetraone (1), 5,8 -dihydroxy-5-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4 -tetraone (2) and 8,5,8-trihydroxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4-tetraone (3) from the chloroform fraction of Diospyros lotus roots. The pure constituents (1-3) were evaluated for their urease inhibitory activity. Compounds (1-3) exhibited potent activity with IC50 value of 28.27 ± 1.68, 20.57 ± 2.00, 27.12 ± 2.45 µM respectively, when compared with standard thiourea (IC50 = 21.23 ± 0.12 µM). The pure isolated compounds (1-3) were also subjected to in silico studies to know their binding pattern with enzyme. The binding orientation and interactions with the important residues of urease enzyme revealed that the three compounds inactivate the enzyme activity by interacting with Ni bi-center as well as with the tailpiece residues.

Background: To date, no optimal way of organizing and delivering care to hypertensive patients at the primary carer level has been identified, due to which a significant number of patients fail to meet the treatment goals. The current study aims to observe hypertension educational intervention's effect on general physicians (GPs) to indirectly improve blood pressure control and patient outcomes. Methodology: In this randomized control trial, GPs will be divided into 2 groups and both groups will be asked to fill hypertension awareness questionnaire at baseline and, after randomization. GPs of the group I will receive (1 day) face-to-face education with structured educational material on hypertension management strategies. GPs of group II will receive the print version of educational material (structured educational material) on strategies of structured hypertension management. Both groups of GPs will recruit 10 (5 newly diagnosed + 5 already diagnosed patients) from the study site. The patient will be asked to fill hypertension awareness questionnaire at baseline and share a 12-hour blood pressure measurement. GPs and patients will be reassessed after 3 months of intervention. Discussion: The purpose of designing this study is to observe the effect of hypertension educational intervention for general physicians to improve blood pressure control and patient outcomes indirectly. Results of this study may provide a basis for developing a hypertension educational program targeted at general physicians. Trial registration: The trial was registered with ClinicalTrials.gov NCT05038774.

COVID-19 (SARS-CoV-2) is a viral disease that causes acute respiratory syndrome, which has increased the morbidity and mortality rate throughout the world. World Health Organization has declared this COVID-19 outbreak as pandemic and classified health emergency throughout the world. In the recent past, outbreaks of SARS and MERS have shown the interspecies transmission potential of coronaviruses and limitations of already prescribed drugs to overcome this global public health issue. Therefore, there is a dire need to identify a new regimen of targeted drugs from natural compounds having anti-COVID19 potential. This study aimed at screening 1018 brown algal natural compounds (many of them previously reported to have immunomodulatory effects) having probable anti-COVID19 potentials. The source compounds were extracted from MarinLit, a database dedicated to marine natural products and screened against COVID-19 main protease. The top seven compounds were further analysed, and their interactions with the active site were visualized. This study will further warrant screening the potent compounds against the virus in in-vitro conditions.

The study aimed to validate the folkloric medicinal uses of Viburnum grandiflorum. The column chromatography led to the isolation of a compound from the chloroform soluble fraction of V. grandiflorum which was characterized as 2, 3-dihydro-2-(4ʹ-hydroxy, 3ʹ-methoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl) 7-hydroxybenzofuran (benzofuran) on the basis of various spectroscopic techniques. When benzofuran was studied for xanthine oxidase inhibition, it caused significant concentration dependent inhibition of the enzyme with IC50: 49.52 µM, however, it was found less potent than standard xanthine inhibitor allopurinol (IC50: 0.59 µM). Binding orientation and binding energy of benzofuran and allopurinol were predicted via docking studies. Docking simulations revealed that both studied molecules interact with key amino acid residues through hydrogen bond (Arg 880, Glu 1261, Thr1010 with Allopurinol & Thr 1010 with benzofuran) and hydrophobic interactions (Phe914, Phe1009 with Allopurinol & Phe 910, Phe 1009 with benzofuran). A fair correlation between the computed binding energy and experimental values was observed. Thus, it is concluded that the isolated compound, benzofuran had inhibition on xanthine oxidase, need further detail studies.

Diabetes is a chronic condition which is locally managed through the stem of Ficus foveolata. To find the exact chemical constituent responsible for this activity, a triterpene lactone (ficusonolide) isolated from F. foveolata was studied for antidiabetic potential through the in vitro antidiabetic paradigm employing L-6 cells and an in vivo antidiabetic assay against non-insulin-dependent rats. The results on glucose uptake in the L-6 cell line indicated that ficusonolide has enhanced the uptake of glucose by 53.27% over control at a dose of 100 μg/mL, while at doses of 50 and 25 μg/mL, the glucose uptake was enhanced by 22.42 and 14.34%, respectively. The extract of F. foveolata (100 mg/kg) and ficusonolide (50 mg/kg) demonstrated a significant (p < 0.001) decline in streptozotocin-induced hyperglycemia of diabetic rats. Ficusonolide displayed conspicuous inhibitory activity against the molecular docking studies with proteins such as dipeptidyl peptidase-IV (DPP-IV), protein tyrosine phosphatase 1B (PTP-1B), α-glucosidase, and α-amylase subjected to molecular targets. Detailed computational and structural insights affirmed promising interactions between target proteins and ficusonolide. In conclusion, the plant and its isolated compound have significant antidiabetic activity with a possible mechanism of interaction with DPP-IV, PTP-1B, α-glucosidase, and α-amylase.

Tobacco (Nicotiana tabacum) is an herbaceous plant originating from South America and processed into cigarettes for consumption. Polyphenols are considered vital components of tobacco in view of their contribution to antioxidant properties. This study aimed to determine the phenolic compounds in different tobacco varieties by applying cold extraction with methanol and distilled water. The extracts were screened for phenolic compound diversity and distribution as well as their antioxidant potential in different tobacco varieties. The results showed that the methanolic extract of tobacco SP-28 exhibited the highest value in the total phenolic content (24.82 ± 0.07 mg GAE/gd.w.) and total flavonoid content (4.42 ± 0.01 mg QE/gd.w.), while the water extract of tobacco SN-2 exhibited the highest value in the total condensed tannin (1.12 ± 0.03 mg CE/gd.w.). The radical scavenging capacities of tobacco SP-28 were relatively high in DPPH (18.20 ± 0.01 mg AAE/gd.w.) and FRAP (3.02 ± 0.10 mg AAE/gd.w.), whereas the ABTS value was the highest in tobacco SN-2 (37.25 ± 0.03 mg AAE/gd.w.), and the total antioxidant capacity was the highest in tobacco SN-1 (7.43 ± 0.18 mg AAE/gd.w.). LC-ESI-QTOF-MS/MS identified a total of 49 phenolic compounds, including phenolic acids (14), flavonoids (30), and other polyphenols (5) in four different tobacco varieties. Tobacco SP-28 showed the highest number of phenolic compounds, especially enriched in flavones. Our study highlights the antioxidant potential of tobacco extracts and reveals the phenolic distribution among different tobacco varieties that could support tobacco utilization in different pharmaceutical industries.

The aim of the present investigation was to evaluate the effect of the combined crude extract, fractions, and compound 1 isolated from the fruits of Datura metel against selected microbial (bacteria and fungi) strains. Results of antibacterial screening indicated marked susceptibility of the extract and its fractions against tested bacterial strains. Among the extract and various fractions, the chloroform fraction exhibited a significant effect against different bacterial strains including Escherichia coli, Staphylococcus aureus, and Bacillus subtilis with an inhibitory zone ranging from 18 to 24 mm. Similarly, results of antifungal activity revealed that the chloroform fraction displays a promising effect against various fungal strains. The chloroform fraction was subjected to repeated chromatography analysis, which yielded compound 1 (daturaolone). Daturaolone exhibited potent activity against selected bacterial strains including Klebsiella pneumoniae, B. subtilis, S. epidermidis, and S. aureus with an inhibitory zone ranging from 12 to 30 mm. In addition, the extracts and daturaolone exhibited significant sensitivity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata. Taken all together, it is concluded that our findings validated the traditional use of D. metel to treat various infectious diseases, which is supported by daturaolone.

Background: Cancer being a genetically heterogeneous and complex disease and the available therapies are not very effective, rendering them the predominant cause of mortality across the world. The discovery of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals. Objective: The current study focused on the anticancer potential of two known dimeric napthoquiones, diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus. Methods: In vitro Epstein-Barr-Virus (EVA) an early antigen activation assay was used to evaluate the antitumor potential of tested compounds followed by a two-stage carcinogenesis assay on mouse skin for anti-carcinogenic effect. Compounds were also assessed for their multidrug resistance reversal potential. The in vitro heatinduced protein denaturation assay was used for the anti-inflammatory effect of the tested compounds. Results: Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at a concentration of 1000 (mol / ratio 32 pmol TPA). In a two-stage carcinogenesis assay on mouse skin, both compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect at 14th week, whereas compound 2 exerted the same effect at 13th week, while both provoked 100% effect at 20th week. Both compounds significantly attenuated thermal-induced protein denaturation with EC50 values of 298 and 264 μg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion of Multidrug-Resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited promising MDR reversal effect in a dose-dependent manner against mouse T-lymphoma cell line. Docking results also showed that both compounds have good docking statistics as compared with standard. Conclusions: Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR reversal effects with significant attenuation of thermal-induced denaturation of the protein. These compounds may explain the traditional uses of D. lotus which might be effective anticancer agents.

Specific cellular uptake and sufficient drug release in tumor tissues are important for effective cancer therapy. Hyaluronic acid (HA), a skeleton material, could specifically bind to cluster determinant 44 (CD44) receptors highly expressed on the surface of tumor cells to realize active targeting. Cystamine (cys) is sensitive highly reductive environment inside tumor cells and was used as a connecting arm to connect docosahexaenoic acid (DHA) and chlorin e6 (Ce6) to the HA skeleton to obtain redox-sensitive polymer HA-cys-DHA/Ce6 (CHD). Nanoparticles were fabricated and loaded with chemotherapeutic drug docetaxel (DTX) by physical encapsulation. The prepared nanoparticles had significantly increased uptake by MCF-7 cells that overexpressed CD44 receptors, and DTX was effectively released at high reducing condition. Compared with mono-photodynamic therapy (PDT) or mono-chemotherapy, the prepared nanoparticles exhibited superior anti-tumor effect by inhibiting microtubule depolymerization, blocking cell cycle and generating reactive oxygen species (ROS). In vivo anti-tumor experiments proved that DTX/CHD nanoparticles had the best antitumor response versus DTX and CHD nanoparticles under near-infrared (NIR) irradiation. These studies revealed that redox-responsive DTX-loaded CHD nanoparticles held great potential for the treatment of breast cancer.

The Sophora mollis is one of the best anti-inflammatory, antioxidant, and anticancerous plant; therefore, the isolated chemical constituents, that is, scopoletin (1), pinitol (2), 2-propenoic acid, 3-(3,4-dihydroxyphenyl)-octacosyl ester (3), betulin (4), and β-sitosterol glucoside (5) were tested for these folklores. The structures of the isolated compounds were confirmed by 1H NMR, 13C NMR, 2D-NMR, and mass spectral data. The anti-inflammatory, anticancer, antiglycation, and antioxidant activities of compounds 1-5 were evaluated using different assays. Compound 1 exhibited significant anti-inflammatory effect as it reduced edema of the paw (83.98%), which is more potent than the standard drug (ibuprofen) (which showed an inhibition percentage of 73.22% a), followed by compound 3. Furthermore, compound 3 showed significant free-radical scavenging activity using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free-radical assay. Percentage inhibition of DPPH recorded was 95.646 ± 0.003, 94.766 ± 0.014, and 94.516 ± 0.011% at concentrations of 400, 200, and 100 μg/mL, respectively. Evaluation of anticancer activity of isolated compounds reveals weak effect against HeLa and 3T3 cell lines. Docking studies of the most active compound into the binding sites of cyclooxygenase isoforms showed a better antagonistic potential against COX-1 than the COX-2 isoform.

Pistacia integerrima leaf galls are used in several traditional medicines to cure many diseases such as diarrhea, asthma, fever, cough, vomiting, and hepatitis. The main goal of the present investigation was to assess the antidiarrheal effect of the Pistacia integerrima extracts/fractions and four isolated flavonoid compounds (1-4) on mice. An in vivo assay involving castor-oil-induced diarrhea was used to evaluate the antidiarrheal potential of extracts/fractions at 100, 200, and 400 mg/kg p.o., as well as isolated compounds at 5, 10, and 20 mg/kg p.o. Pretreatment of mice with extracts/fractions significantly attenuated castor-oil-induced diarrhea in a dose-dependent manner. Among all crude extracts and fractions, the ethyl acetate extract was the most effective with 100% protection against diarrhea followed by chloroform (75% protection) at 400 mg/kg p.o. Although all the isolated compounds exhibited strong antidiarrheal activity, isolated compounds 1 and 4 demonstrated 100% protection against diarrhea. Moreover, docking models were performed using the Molecular Operating Environment (MOE) and AutoDock software and suggested that the extracts and isolated compounds exert antidiarrheal activity by inhibiting mu-opioid and delta-opioid receptors. Therefore, our finding affords a strong pharmacological basis for the traditional use of P. integerrima galls in the treatment of diarrhea.

International audience; Diabetic neuropathy (DN) is a common and serious diabetes-associated complication that primarily takes place because of neuronal dysfunction in patients with diabetes. Use of current therapeutic agents in DN treatment is quite challenging because of their severe adverse effects. Therefore, there is an increased need of identifying new safe and effective therapeutic agents. DN complications are associated with poor glycemic control and metabolic imbalances, primarily oxidative stress (OS) and inflammation. Various mediators and signaling pathways such as glutamate pathway, activation of channels, trophic factors, inflammation, OS, advanced glycation end products, and polyol pathway have a significant contribution to the progression and pathogenesis of DN. It has been indicated that polyphenols have the potential to affect DN pathogenesis and could be used as potential alternative therapy. Several polyphenols including kolaviron, resveratrol, naringenin, quercetin, kaempferol, and curcumin have been administered in patients with DN. Furthermore, chlorogenic acid can provide protection against glutamate neurotoxicity via its hydrolysate, caffeoyl acid group, and caffeic acid through regulating the entry of calcium into neurons. Epigallocatechin-3-gallate treatment can protect motor neurons by regulating the glutamate level. It has been demonstrated that these polyphenols can be promising in combating DN-associated damaging pathways. In this article, we have summarized DN-associated metabolic pathways and clinical manifestations. Finally, we have also focused on the roles of polyphenols in the treatment of DN.

Medicinal plants are precious gifts of nature, which may serve as a source of food and medicine to humans. Phyllanthus emblica L has held a unique position in the Indian (Ayurvedic), Turkish, Unani, and Tibetan medicinal systems for centuries. Its nutritional, therapeutic and healing potentials have made it a valid research option for the development of novel drug formulations with few side effects. The presence of vitamin C, alkaloids, ellagitannins, gallic acid, emblicanin A and emblicanin B, flavonoids (especially rutin and quercetin), and a variety of biological molecules, makes P. emblica, a valued medicinal plant. This review article summarizes the recent literature relevant to the nutritional, health, and therapeutic benefits of P. emblica, such as potential chemo-preventive, anti-diabetic, anti-microbial, anti-inflammatory, analgesic, anti-mutagenic, antioxidant, diuretic, aphrodisiac, UV protectant, and anti-aging activities. Its applications in memory enhancing, respiratory, skin and ophthalmic disorders, and detoxification including that of snake venom, are also highlighted. It additionally reviews retrospective studies on P. emblica at the molecular level, for disease management and control. P. emblica is an important medicinal plant with many benefits. It has been used for centuries and generations as a source of food because of its unique restorative and rejuvenating potential. Thus, in light of the sum of these investigations, new studies could be designed to explore valuable bioactive compounds present throughout in nature in the form of plants

The inadequate role of silver nanoparticles is evident from their underutilization in myriad applications in the modern era. Herein we report the environment-friendly, facile, and robust synthesis of silver nanoparticles (Ag-NPs) from alcoholic extracts of black cumin (Bunium persicum) seeds to reduce and stabilise agents. The extract principally consists of nigellon, terpenoid, thymoquinone, polyene, phenylpropanoids, and phototoxic furanocoumarins. The effect of pH revealed that the BCS@Ag-NPs were more stable at neutral pH than acidic and basic. A change in the size and number of BCS@Ag-NPs was observed at high sodium chloride solution concentrations showing their instability in a concentrated salt solution. The synthesized BCS@Ag-NPs were considered significant catalysts showed by approximate 99% conversion of the 4-nitrophenolate anion into 4-aminophenol in 24 min. The surface plasmon resonance of BCS@Ag-NPs at 430 nm was recorded on UV–Vis spectrometer, and particle size ranging from 35 to 77 nm was measured through scanning electron microscopic (SEM) analysis. FTIR spectra confirmed the presence of amines, alcohols and amide functional groups at 3365 cm−1, 1646 cm−1 and 1026 cm−1 capped along with the reduction of BCS@Ag-NPs. The firm peaks for Ag atoms in BCS@Ag-NPs at almost 0.4, 3.1 and 3.2 keV in EDX analysis showed the presence of elemental silver. Nevertheless, the alcoholic seed extract and synthesized BCS@Ag-NPs exhibited excellent various pharmacological activities. Both the tested samples significantly inhibited Urease, CA-II, PDE-I. The inhibitory potential against tyrosinase was appreciated against extract as compared to BCS@Ag-NPs. The alcoholic extract was effective in the inhibition of E. coli. Both of the tested samples proved significant analgesia in the acetic acid-induced writhing model. A noticeable sedative response was observed as a compared extract. No mortality was detected in acute toxicity. In conclusion, these results provide the scientific rationale to the folklore of black cumin for GIT problems, hypertension, bronchodilation and analgesic.

Marine organisms are considered a cache of biologically active metabolites with pharmaceutical, functional, and nutraceutical properties. Among these, marine bioactive peptides (MBAs) present in diverse marine species (fish, sponges, cyanobacteria, fungi, ascidians, seaweeds, & mollusks) have acquired attention owing to their broad-spectrum health-promoting benefits. Nowadays, scientists are keener exploring marine bioactive peptides precisely due to their unique structural and biological properties. These MBAs have reported ameliorating potential against different diseases like hypertension, diabetes, obesity, HIV, cancer, oxidation, and inflammation. Furthermore, MBAs isolated from various marine organisms may also have a beneficial role in the cosmetic, nutraceutical, and food industries. Few marine peptides and their derivative are approved for commercial use, while many MBAs are in various pre-clinical and clinical trials. This review mainly focuses on the diversity of marine bioactive peptides in marine organisms and their production procedures, such as chemical and enzymatic hydrolysis. Moreover, MBAs' therapeutic and biological potential has also been critically discussed herein, along with their status in drug discovery, pre-clinical and clinical trials.

Anti-inflammatory, analgesic, and sedative medicine is used with numerous side effects, including peptic ulcer, headache, addiction, and other complications. In this regard, discovery research is undergoing a process to discover effective, safe, and economical drugs with no side effects. The aim of this study was to assess chloroform extracts and isolated compounds for anti-inflammatory, analgesic, and sedative activities in animal models. The anti-inflammatory potential was measured by using the carrageenan-induced and histamine-induced paw edema procedure, while the analgesic potential was determined using a hot plate analgesiometer. The sedative effect was observed in an animal model for screening of the locomotor effect of the extract and isolated compound 1. Our data exhibited that the extract and compound 1 attenuated carrageenan-induced and histamine-induced paw edema (93.98 and 89.54%, respectively). Furthermore, compound 1 attenuated biphasic edema associated with histamine and prostaglandins. The chloroform extract showed a moderate analgesic effect; however, compound 1 showed a significant analgesic potential (p < 0.001) by increasing the latency time of the animals in the thermally induced algesia model. Compound 1 exhibited a significant sedative effect and dose-dependent analgesic activity. It is concluded that the chloroform extract and compound 1 showed remarkable anti-inflammatory, analgesic, and sedative activities. This research work strongly rationalizes the folkloric usage of Diospyros kaki in the treatment of inflammation, pain, and insomnia.

Graphical abstract, Highlights • The antidiarrheal activity of C. reflexa was evaluated in pigeons using the juice, aqueous, and methanol extracts. • The antidiarrheal effect of C. reflexa was evaluated using different reported research models. • The juice, aqueous, and methanol extract of C. reflexa exhibit significant anti-motility and anti-secretory potential., Background Cuscuta reflexa (dodder) belonging to the family Convolvulaceae has many ethno-medicinal uses such as antidiarrheal and antiemetic. This plant has been employed to treat diarrhea, where the antidiarrheal use of this plant is well established in different communities around the world without scientific bases. In addition, the antibacterial, anthelmintic, anticholinergic, and antihistaminic effects of this parasitic vine are partly responsible for the folkloric antidiarrheal use of this plant. In the present study, the antidiarrheal activity of C. reflexa was evaluated in pigeons (Columba livia) using the juice (JCR), aqueous (CRAE), and methanol (CRME) extracts. Methods The antidiarrheal effect of C. reflexa was evaluated using different reported research models, with few modifications. In pigeons, diarrhea was induced by administration of castor oil (6 mL/kg, PO), ampicillin (250 mg/kg, IP), magnesium sulfate (2 gm/kg, PO), and cisplatin (6 mg/kg, IV). In these experiments, loperamide (2 mg/kg, IM) was used as a positive control, whereas JCR (1 mL/kg (1%) and 1 mL/kg (2%), CRAE (50, 100 and 200 mg/kg) and CRME (50, 100 and 200 mg/kg) were administered intramuscularly at different doses into each pigeon in the test groups. Results In addition to cisplatin-induced diarrhea, all paradigms tested gave significant results (P < 0.01). The JCR, at different doses, exhibited a significant (p < 0.01) a dose-dependent antidiarrheal effect on both the frequency and the onset of diarrhea. Similarly, CRAE and CRME, at doses of 100 and 200 mg/kg, showed considerable (p < 0.001) inhibition against the onset and frequency of diarrhea. On the other hand, JCR, CRAE, and CRME exerted significant effects (p < 0.001) on the percentage inhibition (PI) of diarrhea and gastrointestinal charcoal transit in a dose-dependent manner. In this respect, the maximum PI (p < 0.01) of JCR, CRAE, and CRME in different experimental paradigms was 43.13, 49.14, and 55.99 %, respectively. Conclusions Taken all together, results from this study reveal that the juice, aqueous, and methanol extract of C. reflexa exhibit significant anti-motility and anti-secretory potential. These findings may explain the medicinal use of C. reflexa in folk medicine as an antidiarrheal medicinal plant.

The main aims of this investigation were the isolation of dimeric naphthoquinones, a new class of dinaphthodiospyrols (1-7), from chloroform fractions and screening them for antibacterial, antifungal, and antioxidant potential. The susceptibility of the isolated compounds, namely, dinaphthodiospyrol A (1), dinaphthodiospyrol B (2), dinaphthodiospyrol C (3), dinaphthodiospyrol D (4), dinaphthodiospyrol E (5), dinaphthodiospyrol F (6), and dinaphthodiospyrol G (7) was assessed for antibacterial potential using well diffusion methods. The isolated compounds showed excellent antibacterial activity against selected bacterial strains, including Gram-positive Bacillus subtilis, Streptococcus epidermis, and Bacillus subtilis, and Gram-negative bacteria Klebsiella pneumonia with the zones of inhibition 6 to 26 nm. The standard drug Imipenem showed a maximum inhibitory zone 30 to 35 nm. Similarly, the isolated compounds were screened for antifungal properties, which showed an excellent reduction in the growth of selected fungal strain including Candida albicans, Aspergillus flavus, Fusarium solani, Trichyton logifusus, Microsporum canis , and Candida glabrata. Among all the screened compounds, 7 exhibited good activity (30-49 mm), followed by compounds 5 and 6, (35-46 mm), while compounds 1-4 showed a moderate effect (8-28 mm) against the selected fungal strain against miconazole which showed potent effects (101-110.98 mm). The isolated compounds were also screened for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) activity. In vitro-based free radical was employed using ascorbic acid as a standard antioxidant. The tested compounds (1-7) exhibited significant antioxidant activity in a concentration-dependent manner. The dinaphthodiospyrol 7 exhibited 97.32% scavenging activity, followed by dinaphthodiospyrol 6, 92.01%, and compounds 5 and 4 with 89.90 and 88.43% scavenging activity at 100 μg/mL, respectively; ascorbic acid showed 96.45% scavenging effect. Furthermore, docking analysis was performed to know the exact binding mode of the tetra-substituted derivatives of dinaphthodiospyrols to the selected target proteins. From the docking analysis, it was found that the docking results are well correlated with the experimental observations. In conclusion, the dinaphthodiospyrols exhibited excellent antibacterial, antifungal, and free radical scavenging potential.

Fernandoa adenophylla (Wall. ex G. Don) Steenis is traditionally used to cure various diseases and can be included as an ingredient in massage oils, which are supposed to comfort muscular tension and pain. This study was designed to assess the antinociceptive, muscle relaxant, and molecular docking properties of a novel compound, namely, (5aR,5a1R,6R,7aS,14bR,15R)15-hydroxy-7a-methyl-6-(2-methylprop-1-en-1-yl)-7,7a,14b,15-tetrahydro-5H-t-5a,15methanobenzo[g]benzo[5,6]azuleno[1,8-bc]chromene-5,9,14,16(5a1H,6H)- tetraone (peshawaraquinone), isolated from the methanolic extract of F. adenophylla in an animal model. The chemical structure of the isolated compound was elucidated using advanced spectroscopic techniques and further confirmed by XRD analysis. Compound 1 was tested against hot plate-induced noxious stimuli at various doses (2.5, 5, 10, and 15 mg/kg i.p.). The muscle relaxation potency of compound 1 was evaluated in the inclined and traction test, while the open-field test was used for the determination of sedative potential. The isolated compound was also subjected to acute toxicity analysis. The compound was then subjected to molecular docking analysis to determine the exact mechanism of action. Compound 1 demonstrated significant (p < 0.05) analgesic effect in a dose-dependent manner. A noticeable muscle relaxant effect was observed with the passage of time in both experimental models. The compound 1 showed a significant (p < 0.05) sedative effect, and in an acute toxicity study, the compound 1 was devoid of any noxious effects. The docking studies showed preferential affinity for μ-opioid and GABAA receptors. Hence, the prospective antinociceptive and muscle relaxant and sedative properties are probably mediated through these two target interactions.

Heterophragma adenophyllum (Wall. ex G.Don) Seem belong to family Bignoniacea. To find a safe, effective and economical drugs candidate, the screening of chemical constituents for various biological actions is essential. The isolated compounds (1–3), such as, 2-hydroxy-3-(3-methylbut-2-enyl)naphthalene-1,4-dione (1), methyl 1,2-dihydroxy-2-(3-methylbut-2-enyl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylate (2), 2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10-dione (3) were characterized with 1H-NMR, 13C-NMR, EI-MS and UV spectroscopy. The pure constituents have shown significant inhibition potential against phosphodiesterase-1 (PDE-1) with percentage inhibition 98.4, 92.4 and 88.4%, respectively. The IC50 value of the compounds was calculated in which all the three compounds have shown potent activity against clinically important enzyme PDE-1 (IC50 = 21.9 ± 1.12 to 112.4 ± 2.08 µM). When these values were compared with standard EDTA (IC50 = 265.5 ± 2.25 µM), then it is concluded that H. adenophyllum can be used for the treatment of vasoconstriction and various inflammatory conditions. Molecular docking was performed to explore the possible role of isolated bioactive compounds into active sites of snake venom and human PDE-1. The data obtained in terms of binding energy values from docking studies of both snake venom and human PDE-I agrees with the experimental PDE-1 inhibition.

Carbonic anhydrase-II (CA-II) catalyzes reversible hydration of carbon dioxide leading to the formation of bicarbonate and a proton. CA-II inhibitors act as biomarkers and therapeutic targets for various diseases such as epilepsy, glaucoma, leukemia, and cystic fibrosis. In the present work, a number of thiourea and benzylidene derivatives were evaluated as CA-II inhibitors. For this, detection of CA-II inhibition was tested through high throughput biochemical mechanism-based assay. Results indicated that thiourea derivatives exhibit remarkable inhibition activity with IC50 values ranging from 1.90 ± 1.30 to 25.90 ± 2.05 µM, when compared with the standard inhibitor acetazolamide IC50 = 0.13 ± 0.05. On the other hand, bezylidene derivatives showed weak inhibition potential with IC50 values in the range of 52.68 ± 0.47 to 348.57 ± 3.32 µM when compared with the thiourea derivatives; the Ez-Fit enzyme kinetics software was used for IC50 calculations from the percentage inhibition. In addition, 3T3 normal cell line was employed to determine the toxicity profile of identified inhibitors of CA-II. In silico modeling was performed to decipher the molecular nature of thiourea and benzylidene derivatives with key residues of carbonic anhydrase; results were in agreement with experiments related to inhibition of carbonic anhydrase.

Human Parainfluenza virus (HPIV) causes lower respiratory tract infections (LRTI) mostly in young children. Respiratory viral infections may decline T cells in circulation and display enhanced pathogenicity. This study is aimed to analyze T cells alterations due to HPIV in children with LRTIs. Children (N=152) with bronchitis or pneumonia, admitted in tertiary care hospitals were included in the study. Respiratory samples (throat or nasopharyngeal swabs) were taken and HPIV genotypes (1-4) were analyzed through RT-PCR. Peripheral blood T cells, CD3+, CD4+, CD8+, and CD19+, were analyzed in confirmed HPIV positive and healthy control group children through flow cytometry. The positivity rate of HPIV was 24.34% and the most prevalent genotype was HPIV-3 (20.40%). HPIV-1 and HPIV-2 were detected in 0.66% and 02% children respectively. The T lymphocyte counts were observed significantly reduced in children infected with HPIV-3. CD4+ cell (1580 ± 97.87) counts did not change significantly but the lowest CD8+ T cell counts (518.5 ± 74.00) were recorded. Similarly, CD3+ and CD19 cell ratios were also reduced. The CD4/CD8 ratio was significantly higher (3.12 ± 0.59) in the study population as compared to the control group (2.18±0.654). Changes in the count of CD8+ T cells were more pronounced in patients with bronchiolitis and pneumonia. It is concluded that CD8+ T cells show a reduced response to HPIV-3 in children with severe LRTIs suggesting a strong association of these cells with disease severity.

The human communities all over the globe, are suffering from emerging and growing of a serious public health problem, the antimicrobial-resistant pathogens, which are resistant to almost all antibiotic classes. This happens in parallel with the decreasing investment in antimicrobial research and development by major pharmaceutical companies as an expensive and high-risk investment. In order to eliminate that phenomenon, the richness and diversity of nature must be taken into account as a cheap and reliable source for antimicrobial drugs. The significance of antimicrobial peptides (AMPs) of insects is widely studied. The source and the method of activity on the insect’s immune system in the susceptible arrangement of these particles have been depicted from alternate points of view. The current short-review is briefly highlighted in this interesting topic.&nbsp

The aim of the current research finding was to synthesize, characterize and antibacterial evaluation of sparfloxacin-mediated noble metal nanoparticles. Noble metal [silver (Ag), and gold (Au)] nanoparticles (NPs), mediated with fluoroquinolone, an anti-bacterial drug [Sparfloxacin, (Sp)], was synthesized by a facile and convenient procedure. Formulated Ag-Sp NPs, and Au-Sp NPs exhibited stability against variation in pH, NaCl solution, temperature, and time. The structural topographies of Ag-Sp, and Au-Sp NPs were determined by fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy (UV-Vis), scanning electron microscopy (SEM) atomic force microscopy (AFM), and energy dispersive X-ray (EDX). UV-Vis revealed the formulation of NPs by showing typical surface Plasmon absorption maxima at 410 nm for Ag-Sp NPs and 555 nm for Au-Sp NPs. The AFM and SEM analysis ascertained stable mono dispersed Ag-Sp NPs and Au-Sp NPs in the size range of 40-50 nm, and 70-80 nm, respectively. Ag-Sp, and Au-Sp NPs exhibited antibacterial traits against Bacillus subtilis, Staphylococcus aureus, and Klebsiella pneumonia, showing a zone of inhibition (ZOI) ranging from 20±0.98 mm to 24±0.94 mm (Ag-Sp NPs), and 22±0.79 mm to 26±0.92 mm (Au-Sp NPs) at dose of 3 mg/mL.

Graphical abstract, Cuscuta reflexa has been traditionally used as an antiemetic. Additionally, it has been used in various herbal formulations for the treatment of emesis. So far, there is no scientific evidence of the plant extract as antiemetic. Therefore, this study was intended to assess the antiemetic activity of Juice (JCR), aqueous (CRAE) and methanolic extract (CRME) of C. reflexa in pigeons. Emesis was induced through GIT irritants like ampicillin (300 mg/kg, IM), copper sulphate (100 mg/kg, PO), conc. sodium chloride solution (1600 mg/kg, PO) and cisplatin (5-HT3 receptor stimulator) (6 mg/kg, IM). Dimenhydrinate acted as a positive control (2 mg/kg; IM). JCR [(1 ml/kg (1 %) and 1 ml/kg (2 %)], CRAE, and CRME were administered intramuscularly at different doses (50, 100 and 200 mg/kg) to each pigeon (n = 6). In each group, calculation of total number of jerks & vomiting episodes, and vomiting-weight was carried out to evaluate its antiemetic activity. The JCR exhibited a significant (p < 0.05) antiemetic impact on both the frequency and onset of emesis at 1 ml/kg (2 %) against various emesis mediator, except sodium chloride. Similarly, CRAE and CRME elicited marked dose dependent inhibition both on onset and frequency of emesis with highly significant (p < 0.001) effect at 200 mg/kg. The study reflects that juice, aqueous and methanolic extract of C. reflexa have significant antiemetic potential and possess pharmacological active constituent(s) that interfered with the emetic mediators by acting through GIT irritation and 5-HT3 receptor stimulations. Results of this study provide a scientific background to its traditional antiemetic uses.

Heterophragma adenophyllum (HA) is an important medicinal plant which is used in traditional medicine for the treatment of muscular tension and pain. Herein, we report the isolation of methyl,1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylate (1), from the roots of H. adenophyllum. The isolated compound 1 was evaluated for in vivo muscle relaxant, sedative, and analgesic potential in Swiss albino mice. Results revealed that the isolated compound 1 exhibited a dose- and time-dependent muscle coordination (51%) and a significant (p p 1. Furthermore, the experimental results were compared with the theoretical studies by using density functional theory (DFT). The stability of the compound as well as the flow of electrons was determined by the calculated Frontier orbital analysis. The calculated stretching frequencies, 1H-NMR/13C-NMR chemical shift values and UV-visible spectra were found to be in agreement with experimental values. The results obtained from molecular docking studies were used to explore the mechanism of analgesic and muscle relaxant activity. Communicated by Ramaswamy H. Sarma

At present, malignant tumours have become one of the most serious diseases that endanger human health. According to a survey on causes of death in Chinese population in early 1990s, the malignant tumours were the second leading cause of death. In the treatment of tumours, the ideal situation is that drugs should target and accumulate at tumour sites and destroy tumour cells specifically, without affecting normal cells and stem cells with regenerative capacity. This requires drugs to be specifically transported to the target organs, tissues, cells, and even specific organelles, like mitochondria, nuclei, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus (GA). The nano drug delivery system can not only protect drugs from degradation but also facilitate functional modification and targeted drug delivery to the tumour site. This article mainly reviews the targeting of nano drug delivery systems to tumour cytoplasmic matrix, nucleus, mitochondria, ER, and lysosomes. Organelle-specific drug delivery system will be a major mean of targeting drug delivery with lower toxicity, less dosage and higher drug concentration in tumour cells.

BackgroundAnalgesic, anti-inflammatory, and sedative drugs are available with potential side effects such as peptic ulcer and addiction among other things. In this regard, research is underway to find safe, effective, and economical drugs free of these side effects. In this study, an isolated natural product fromDiospyros lotus, was tested for the aforementioned bioactivities.ObjectivesTo evaluate analgesic, anti-inflammatory, and sedative potential ofD. lotusextracts in animal paradigms using BALB/c mice as experimental model.MethodsAnalgesic, anti-inflammatory and sedative activities of dinaphthodiospyrol G (1) isolated from the chloroform fraction ofD. lotuswere evaluated using different experimental procedures. Anti-inflammatory effect was evaluated using the carrageenan and histamine-induced paw edema, whereas the antinociceptive effect was quantified by means of the hot plate analgesiometer. On the other hand, the sedative effect was determined using animal assay for screening the locomotors effects of compound1. Compound1was also subjected to molecular modeling studies against cyclooxygenase enzymes.ResultsResults from this investigation showed that the extract is devoid of anti-inflammatory and antinociceptive potentials but has a significant sedative effect, whereas the tested compound exhibited 55.23 and 78.34% attenuation in paw edema by carrageenan and histamine assays, respectively. A significant (p 1forms specific interactions with key residues in the active site of the target receptor, which validates the potential use of the isolated compound as cyclooxygenase inhibitor.ConclusionsCompound1exhibited remarkable analgesic, anti-inflammatory, and sedative activities. These findings strongly justify the traditional use ofD. lotusin the treatment of inflammation, pain, and insomnia.

Sclerosing lipogranuloma (SLG) in children is a rare, benign disease of unknown etiology suspected to be due to abnormal fatty tissue reaction. A 13-year-old girl presented with progressively worsening back pain. Cross-sectional imaging identified a retroperitoneal mass compressing the left ureter as well as infrarenal inferior vena cava atresia with extensive venous collaterals and chronic partially occlusive thromboses of the iliac veins. Surgical biopsy was consistent with SLG and it resolved spontaneously. SLG is typically a disease of adulthood but may be seen in children. The association between inferior vena cava atresia with venous thrombosis and development of SLG has not been reported previously.

Diospyros lotus, also known as date-plum, belongs to theEbenaceaefamily and is mostly recognized as a rootstock forD.kaki. Similar classes of naphthoquinones inD.lotusare investigated against cancer and inflammation and have antimicrobial, sedative, and analgesic properties. Six chemical constituents (1-6) were isolated fromDiospyros lotusand tested for anti-inflammatory effects at the dose of 2.5 and 5 mg/kg, i.p., using carrageenan (1%, 0.05 ml)-induced paw edema. The maximum protection against carrageenan-induced edema was observed for compounds 1 and 2. Both studied compounds demonstrated significant anti-inflammatory effect after the 3rdhour of posttreatment. The maximum anti-inflammatory effect of compound 1 was 85.96%, while that of compound 2 was 81.44%, followed by compounds 5 and 6, which exhibited 80.11% and 82.45% effect, respectively. Similarly, histamine-induced inflammation was significantly antagonized by 1, 2, 5, and 6 with 87.99%,82.18±1.8,80.40±1.59, and 77.44% effects, respectively, at 5 mg/kg after the 2ndhour of posttreatment. The rest of the tested compounds did not show any significant effect as compared to the negative control. Interestingly, no toxicity was observed at higher doses. Moreover, the extracted compounds showed remarkable antibacterial activity against the Gram-positive bacteria and no effect against the Gram-negative bacteria. Docking studies on target cyclooxygenases showed that all the compounds established interactions with the key amino acid residues present in the additional pocket of COX-2. Hence, these compounds may act as selective COX-2 inhibitors. In conclusion, the findings of the current study suggest that the roots ofDiospyros lotusmay contain some anti-inflammatory and antibacterial agents with minimal toxicological effects and accordingly this plant product is recommended for further investigations.

Background: Dryopteris cycadina has diverse traditional uses in the treatment of various human disorders which are supported by pharmacological studies. Similarly, the phytochemical studies of this plant led to the isolation of numerous compounds. Methodology: The present study deals with α-glucosidase inhibition of various kaempferol derivates including kaempferol-3, 4/-di-O-α- L-rhamnopyranoside 1, kaempferol-3, 5-di-O-α-L-rhamnoside 2 and kaempferol-3,7-di-O-α- L-rhamnopyranoside 3. Results: The results showed marked concentration-dependent inhibition of the enzyme when assayed at different concentrations and the IC50 values of compounds 1-3 were 137±9.01, 110±7.33, and 136±1.10 mM, respectively far better than standard compound, acarbose 290±0.54 mM. The computational studies revealed strong docking scores of these compounds and augmented the in vitro assay. Conclusion: In conclusion, the isolated kaempferol derivatives 1-3 from D. cycadina exhibited potent α- glucosidase inhibition.

The ubiquitin (Ub)-proteasome system (UPS) is considered as a central protein degradation system in all eukaryotes. The UPS comprises of several factors such as Ub and Ub-like molecules, Ub hydrolases, E3 Ub ligases, and the proteasome itself. Numerous studies have demonstrated that the dysfunction of UPS plays an essential role in the pathogenesis and progression of Alzheimer's disease (AD). Furthermore, current evidence has suggested that the UPS components can be connected with the initial stage of AD that is characterized by synaptic dysfunction, and to the late phases of AD, marked by neurodegeneration. In AD patients, the accumulations of insoluble protein in the brain can be caused by overload or dysfunction of the UPS, or by conformational alterations in the protein substrates that prevent their degradation and recognition by the UPS. Synaptic dysfunction is also caused by defective proteolysis that has found in the initial stage in AD as the UPS is widely recognized to play a pivotal role in the regular activities of synapses. Conversely, its precise cause and pathogenesis are unclear. Presently accepted medicines for AD give symptomatic relief, though they are unable to stop the progression of the disease. Besides, the components of the cellular quality control system demonstrate a significant emphasis on the advancement of targeted and effective treatments for AD. In this review, we focus on the role of UPS in the pathogenesis of AD and highlight how the UPS-linked treatments influence in the management of AD.

Many cases of insecticide resistance in insect pests give resulting no-cost strains that retain the resistance genes even in the absence of the toxic stressor. Malathion (rac-diethyl 2-[(dimethoxyphosphorothioyl)sulfanyl]succinate) has been widely used against the red flour beetle, Tribolium castaneum Herbst. in stored products although no longer used. Malathion specific resistance in this pest is long lasting and widely distributed. A malathion resistant strain was challenged with a range of stressors including starvation, hyperoxia, malathion and a pathogen to determine the antioxidant responses and changes to some lifecycle parameters. Adult life span of the malathion-specific resistant strain of T. castaneum was significantly shorter than that of the susceptible. Starvation and/or high oxygen reduced adult life span of both strains. Starving, with and without 100% oxygen, gave longer lifespan for the resistant strain, but for oxygen alone there was a small extension. Under oxygen the proportional survival of the resistant strain to the adult stage was significantly higher, for both larvae and pupae, than the susceptible. The resistant strain when stressed with malathion and oxygen significantly increased catalase activity, but the susceptible did not. The resistant strain stressed with Paranosema whitei infection had significantly higher survival compared to the susceptible, and with low mortality. The malathion resistant strain of T. castaneum showed greater vigour than the susceptible in oxidative stress situations and especially where stressors were combined. The induction of the antioxidant enzyme catalase could have helped the resistant strain to withstand oxidative stresses, including insecticidal and importantly those from pathogens. These adaptations, in the absence of insecticide, seem to support the increased immunity of the insecticide resistant host to pathogens seen in other insect species, such as mosquitoes. By increasing the responses to a range of stressors the resistant strain could be considered as having enhanced fitness, compared to the susceptible.

Simple Summary Lucerne (Medicago sativa L.) is a cross-pollinated crop and pollination does not usually take place until the sexual column is released. The discharge of the sexual column is referred to as ‘tripping’ the flower. In this study, several bee species were investigated to facilitate the pollination of lucerne crop with a purpose to examine the pollination efficiencies of native insect pollinators that lead to a seed set of alfalfa. We designed a two-year field trial to investigate the abundance and diversity of insect pollinators along with foraging behavior in terms of stay time, visitation rate, pollen harvest and tripping efficiency. Moreover, the single-visit efficiency in terms of number of seeds per pod, germination and seed yield was evaluated. Ten major pollinators (five solitary bees, three honeybees and two flies) were tested for their pollination efficiency as effective pollinators. Findings show the solitary bees (Megachile cephalotes, Megachile hera, Amegilla sp.) can be recommended as an effective pollinator for this crop, thus increasing options available to seed growers. For lucerne seed development, more consideration should be paid to the variety of native wild bees, conservation strategies and foraging requirements in establishing a diverse pollination system rather than a single bee species. Abstract Lucerne (Medicago sativa L.) is a cross-pollinated crop and requires entomophilous pollination for tripping of flowers and subsequent pod and seed set. To discover the best pollinators for lucerne seed production, a two-year field trial was carried out at the research farm of MNS University of Agriculture, Multan, Pakistan. Abundance and diversity of insect pollinators along with the foraging behavior were recorded in terms of tripping efficiency, stay time, visitation rate and pollen harvest. The single-visit efficiency of abundant insect pollinators was also evaluated in terms of number of seeds and seed weight per raceme along with germination percentage. Ten most abundant floral visitors (five solitary bee species, three honeybee species and two syrphid fly species) were tested for their pollination efficiency. Honeybees were most abundant in both the years followed by the solitary bees and syrphid flies. Single-visit efficacy in terms of number of pods per raceme, number of seeds per raceme, 1000 seed weight and germination percentage revealed Megachile cephalotes as the most efficient insect pollinator followed by Megachile hera and Amegilla sp. Future studies should investigate the biology and ecology of these bee species with special emphasis on their nesting behavior and seasonality.

Nickel nanoparticles (Ni NPs) are utilized extensively in various industrial applications. However, there are increasing concerns about potential exposure to Ni NPs and consequent health effects. The aim of this study was to assess Ni NPs-induced liver toxicity in Sprague Dawley rats. Twenty-five rats were exposed to Ni NPs via intraperitoneal injection at doses of 15, 30, and 45 mg/kg per body weight for 28 days. Results from ICP-MS analysis showed an increase in the concentration of Ni NPs in a dose-dependent manner. The liver dysfunction was indicated by considerable production of ALT, AST, ALP, LDH, and TB in Ni NPs-treated rats. Histological examination demonstrated liver injuries (inflammatory cells, congestion, necrosis, and pyknosis) in exposed rats with dose-dependent severity of pathologies by semi-quantitative histograding system. To explore the toxicological pathways, we examined oxidative stress biomarkers and detected Ni NPs significantly elevated the levels of MDA and LPO while decreasing the levels of CAT and GSH. All the changes in biomarkers were recorded in a dose-dependent relationship. In addition, we found upregulated NF-kβ indicating activation of inflammatory cytokines. ELISA results of serum revealed a remarkable increase of nitrative stress markers (iNOS and NO), ATPase activity, inflammatory cytokine (IL-6, IL-1β, and TNF-α), and apoptotic mediators (caspase-3 and caspase-9) in Ni NPs-treated groups than the control. In summary, the result of this study provided evidence of hepatotoxicity of Ni NPs and insightful information about the involved toxic pathways, which will help in health risk assessment and management, related preventive measures for the use of Ni-NPs materials.

Under changing climate, water scarcity and frequent incidence of diseases like stripe rust pose the biggest threat to sustainable crop production which jeopardizes nutritional security. A study was executed to rationalize crop water requirement and evaluate wheat (Triticum aestivum L. cv. Bohoth 3) yield losses by stripe rust infection under irrigated conditions. Seven water treatments included three irrigations in three stages/season ( S 3 ), four irrigations ( S 4 ), and five irrigations ( S 5 ) at the different sensitive growth stages, full ( F ), and two deficit irrigation levels including D 1 = 80 % of field capacity (FC) and D 2 = 70 % (FC) along with farmers’ practice of irrigation as control ( C ). Results revealed that F and D 1 boosted grain yield by 31 and 14%. Overall, F irrigation regime resulted in the highest grain production (2.93 ton/ha) as well as biomass yield (13.2 ton/ha). However, D 2 had the highest value of grain protein (15.9%) and achieved the highest application efficiency (AE) at midseason (54.6%) and end season (59.6%), and the lowest AE was under S 3 . Also, halting irrigation at the milky stage ( S 5 ) led to a significant decrease in irrigation water use efficiency as compared to D 1 . However, cutting irrigation at the end of seedling, heading, and milky stages ( S 3 ) caused a significant reduction in E a , crop water use (ETa), and 1000 grain weight in comparison with all other treatments. Regarding yellow rust, S 3 irrigation regime resulted in the lowest incidence of yellow rust infection. The highest irrigation and water use efficiency values were recorded under D 1 (0.79 and 0.59 kg/m3), and the lowest values were obtained for control. Hence, the deficit irrigation treatment D 1 could be recommended as the best appropriate strategy to save more water and to improve the water productivity under Yemeni agroclimatic conditions.

Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling.