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Abstract Background Wound management is a critical procedure in veterinary practice. A wound is an injury that requires the body’s cells’ alignment to break down due to external assault, such as trauma, burns, accidents, and diseases. Re-epithelization, extracellular matrix deposition, especially collagen, inflammatory cell infiltration, and development of new blood capillaries are the four features that are used to evaluate the healing process. Using a natural extract for wound management is preferred to avoid the side effects of synthetic drugs. The current study aimed to assess the effect of major pregnane glycoside arabincoside B (AR-B) isolated from Caralluma arabica (C. arabica) for the wound healing process. Method AR-B was loaded on a gel for wound application. Rats were randomly distributed into six groups: normal, positive control (PC), MEBO®, AR-B 0.5%, AR-B 1%, and AR-B 1.5%, to be 6 animals in each group. Wounds were initiated under anesthesia with a 1 cm diameter tissue needle, and treatments were applied daily for 14 days. The collected samples were tested for SOD, NO, and MDA. Gene expression of VEGF and Caspase-3. Histopathological evaluation was performed at two-time intervals (7 and 14 days), and immunohistochemistry was done to evaluate α -SMA, TGF-β, and TNF-α. Result It was found that AR-B treatment enhanced the wound healing process. AR-B treated groups showed reduced MDA and NO in tissue, and SOD activity was increased. Re-epithelization and extracellular matrix deposition were significantly improved, which was confirmed by the increase in TGF-β and α -SMA as well as increased collagen deposition. TNF-α was reduced, which indicated the subsiding of inflammation. VEGF and Caspase-3 expression were reduced. Conclusion Our findings confirmed the efficiency of AR-B in enhancing the process of wound healing and its potential use as a topical wound dressing in veterinary practice.

This study addresses a comparative comprehensive metabolic profiling of two Egyptian cultivars of fenugreek (Trigonella foenum-graecum L.) seeds ‘Giza 2’ and ‘Giza 30’ via RP-HPLC-DAD-QTOF-MS and MS/MS. Briefly, 126 metabolites were detected in the samples under investigation, being classified into hydroxybenzoic acids (8), hydroxycinnamic acids (7), flavonoids (49 with a predominancy of flavones in particular apigenin derivatives), coumarins (1), furostanol saponins (17), alkaloids (2), amino acids (11), peptides (2), jasmonates (6), nucleosides (30), organic acids (16), terpenoids (1), and sugars (3). In addition, the total phenolic content and antioxidant activity were determined and compared with other geographically related seeds (chickpea Giza-1, sesame Giza-32, and linseed, Giza-10), showing slight differences among them but higher values than the other geographically related seeds that were segregated from them upon chemometric analysis. This is the first comprehensive metabolic profiling of these cultivars, presenting an initial account of some metabolites found in Fabaceae, such as apigenin di C pentoside, with a significant occurrence of biologically active furostanol saponins. It gives a prospect of fenugreeks richness of bioactive metabolites as an essential functional food that could add value to the food and nutraceutical industries' sustainability.

Abstract Jatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin conditions such as wound healing, as antibacterial and hemostatic. In this study, we evaluated the cytotoxicity and the antiviral activities of the methanolic J. variegata (leaves: Ext-1, stems: Ext-2, and roots: Ext-3), and J. spinosa extracts (aerial parts: Ext-4 and roots: Ext-5), in addition to their methylene chloride fractions of roots extracts (F-6 and F-7, respectively). All samples were tested against three human cancer cell lines in vitro (MCF-7, HepG2, and A549) and two viruses (HSV-2 and H1N1). Both plants showed significant cytotoxicity, among them, the methylene chloride fractions of roots of J. variegata ( F-6 ) and J. spinosa roots (F-7) showed the highest activity on MCF-7 (IC50 = 1.4 and 1 μg/mL), HepG2 (IC50 = 0.64 and 0.24 μg/mL), and A549 (IC50 = 0.7 and 0.5 μg/mL), respectively, whereas the IC50 values of the standard doxorubicin were (3.83, 4.73, and 4.57 μg/mL) against MCF-7, HepG2, and A549, respectively. These results revealed that the roots of both plants are potential targets for cytotoxic activities. The in vitro results revealed potential antiviral activity for each of Ext-3, Ext-5, F-6, and F-7 against HVS-2 with IC50 of 101.23, 68.83, 4.88, 3.24 μg/mL and against H1N1 with IC50 of 51.29, 27.92, 4.24, and 3.06 μg/mL respectively, whereas the IC50 value of the standard acyclovir against HVS-2 was 83.19 μg/mL and IC50 value of the standard ribavirin against H1N1 was 52.40 μg/mL .The methanol extracts of the roots (Ext-3 and Ext-5) of both plants were characterized using UPLC/MS. A total of 73 metabolites were annotated, including fourteen diterpenoids, eleven flavonoids, ten phenolic acid conjugates, twelve fatty acids and their conjugates, five triterpenes and steroids, two sesquiterpenes, and six coumarins. The cytotoxicity and antiviral activities determined in the present work are explained by the existence of flavonoids, coumarins and diterpenes with commonly known cytotoxicity and antiviral activities.

Abstract Background With the emergence of many side effects from synthetic drugs, there is an urgent need to find a natural alternative to these products. Therefore, our primary aim was to evaluate the anti-inflammatory activity of Tamarix aphylla (TA) and investigate the potential mechanism underlying this action. Methods Initially, to ensure the safety of the extract and for dose selection, we performed an acute oral toxicity Assay through the oral administration of graded doses up to 4 g\kg in Wistar rats. then, we used the carrageenan-induced edema model to elucidate the anti-inflammatory activity. Using specific ELISA kits, we measured the levels of TNF-α, IL-1β, COX-2 and NO inside the inflamed paw tissue. Finally, for the in-vitro anti-inflammatory experiment, we used the erythrocyte membrane stability test. Results Based on the acute oral toxicity assay, T. aphylla was considered generally safe and three different doses of 100, 200, and 400 mg/kg were chosen for further experiments. Additionally, TA expressed a significant (P

Abstract Background In the last few decades, the use of plant extracts and their phytochemicals as candidates for the management of parasitic diseases has increased tremendously. Irises are aromatic and medicinal plants that have long been employed in the treatment of different infectious diseases by traditional healers in many cultures. This study aims to explore the potential of three common Iris species (I. confusa Sealy, I. pseudacorus L. and I. germanica L.) against infectious diseases. Their in vitro antiprotozoal potency against Plasmodium falciparum, Trypanosoma brucei brucei, T. b. rhodesiense, T. cruzi and Leishmania infantum beside their cytotoxicity on MRC-5 fibroblasts and primary peritoneal murine macrophages were examined. Methods The secondary metabolites of the tested extracts were characterized by UPLC-HRMS/MS and Pearsons correlation was used to correlate them with the antiprotozoal activity. Results Overall, the non-polar fractions (NPF) showed a significant antiprotozoal activity (score: sc 2 to 5) in contrast to the polar fractions (PF). I. confusa NPF was the most active extract against P. falciparum [IC50 of 1.08 μg/mL, selectivity index (S.I. 26.11) and sc 5] and L. infantum (IC50 of 12.7 μg/mL, S.I. 2.22 and sc 2). I. pseudacorus NPF was the most potent fraction against T. b. rhodesiense (IC50 of 8.17 μg/mL, S.I. 3.67 and sc 3). Monogalactosyldiacylglycerol glycolipid (18:3/18:3), triaceylglycerol (18:2/18:2/18:3), oleic acid, and triterpenoid irridals (spirioiridoconfal C and iso-iridobelamal A) were the top positively correlated metabolites with antiplasmodium and antileishmanial activities of I. confusa NPF. Tumulosic acid, ceramide sphingolipids, corosolic, maslinic, moreollic acids, pheophytin a, triaceylglycerols, mono- and digalactosyldiacylglycerols, phosphatidylglycerol (22:6/18:3), phosphatidylcholines (18:1/18:2), and triterpenoid irridal iso-iridobelamal A, were highly correlated to I. pseudacorus NPF anti- T. b. rhodesiense activity. The ADME study revealed proper drug likeness properties for certain highly corelated secondary metabolites. Conclusion This study is the sole map correlating I. confusa and I. pseudacorus secondary metabolites to their newly explored antiprotozoal activity.

Abstract Background Breast cancer is a prevalent malignant tumor that affects women worldwide. The primary challenge in treating breast cancer is combating drug resistance, which contributes to relapse and metastasis. Jatrophone is a unique macrocyclic jatrophane diterpene found in various Jatropha and Euphorbia species. It possesses diverse biological and pharmacological activities, including anticancer activity. However, it is unclear whether jatrophone can overcome drug resistance in breast cancer. Methods This study includes the investigation of the cytotoxicity of jatrophone on doxorubicin-resistant breast cancer cells (MCF-7ADR) and the underlying molecular mechanisms. The effects of jatrophone on cell viability were determined using the sulforhodamine B (SRB) assay, while flow cytometry was used to evaluate cell cycle progression, apoptosis, and autophagy. A scratch assay was conducted to observe cell migration, and western blotting was used to measure downstream protein levels (PI3K, AKT, and NF-κB). Unpaired Student’s t-tests were used for comparison between the two groups and the results were analyzed by one-way ANOVA with Tukey- Kremer post hoc test. Results It was shown that jatrophone exhibited potent cytotoxic activity on MCF-7ADR cells in a dose-dependent manner, with an IC50 value of 1.8 µM. It also significantly induced cell cycle S and G/M phase arrest. Interestingly, jatrophone induced both early and late apoptotic cell death, as well as autophagic cell death, with negligible necrosis. Furthermore, jatrophone treatment diminished the migration of MCF-7ADR cells. At the molecular level, jatrophone treatment significantly down-regulated the expression levels of PI3K, AKT, and NF-κB. β. Conclusions The results of the study suggest that jatrophone decreases the proliferation of MCF-7/ADR cells at a low micromolar concentration; induces cell cycle arrest; promotes apoptotic, and autophagic cell death; inhibits migration and EMT; and works on resistance by a mechanism involving the inhibition of the PI3K/Akt/ NF-κB pathway. These findings provide evidence of the potential of jatrophone to be a promising lead compound for targeting doxorubicin-resistant breast cancer cells and could be further investigated for its clinical application as a chemotherapy adjuvant.

Abstract The members of the genus Phyllanthus have long been used in the treatment of a broad spectrum of diseases. They exhibited antiproliferative activity against various human cancer cell lines. Breast cancer is the most diagnosed cancer and a leading cause of cancer death among women. Doxorubicin (DOX) is an anticancer agent used to treat breast cancer despite its significant cardiotoxicity along with resistance development. Therefore, this study was designed to assess the potential cytotoxicity of P. niruri extracts (and fractions) alone and in combination with DOX against naïve (MCF-7) and doxorubicin-resistant breast cancer cell lines (MCF-7ADR). The methylene chloride fraction (CH2Cl2) showed the most cytotoxic activity among all tested fractions. Interestingly, the CH2Cl2-fraction was more cytotoxic against MCF-7ADR than MCF-7 at 100 µg/mL. At sub-cytotoxic concentrations, this fraction enhanced the cytotoxic effect of DOX against the both cell lines under investigation (IC50 values of 0.054 µg/mL and 0.14 µg/mL vs. 0.2 µg/mL for DOX alone against MCF-7) and (1.2 µg/mL and 0.23 µg/mL vs. 9.9 µg/mL for DOX alone against MCF-7ADR), respectively. Further, TLC fractionation showed that B2 subfraction in equitoxic combination with DOX exerted a powerful synergism (IC50 values of 0.03 µg/mL vs. 9.9 µg/mL for DOX alone) within MCF-7ADR. Untargeted metabolite profiling of the crude methanolic extract (MeOH) and CH2Cl2 fraction exhibiting potential cytotoxicity was conducted using liquid chromatography diode array detector-quadrupole time-of-flight mass spectrometry (LC-DAD-QTOF). Further studies are needed to separate the active compounds from the CH2Cl2 fraction and elucidate their mechanism(s) of action.

Abstract Plant resins are rich in bioactive compounds with high medicinal values. However, the chemistry and anti-inflammatory activity of the resins produced by trees of the genus Eucalyptus were scarcely investigated. The inflammatory targets cyclooxygenase-1 (COX-1), COX-2, TNF-, NF-B, and NO were significantly inhibited by the methanolic extract of Eucalyptus maculata kino resin (EME) and its CH2Cl2 soluble fraction (MCF). Sakuranetin (C1), (E)-cinnamic acid (C2), kaempferol 7- methyl ether (C3), 7-O-methyl aromadendrin (C4), and 1,6- dicinnamoyl-O-α-D-glucopyranoside (C5) were isolated from MCF. Three compounds (C1, C2, and C4) showed potent in vitro COX-1 inhibition, while C5 inhibited COX-2, TNF-α, NF-κB, and NO significantly. An in-silico study revealed that C5 had the highest binding affinity to the active site in COX-2 with binding energy score (S) of -14.85 kcal/mol, better than celecoxib (COX-2 inhibitor). In conclusion, 1,6-dicinnamoyl-O-α-D-glucopyranoside (C5) could be investigated further in the search for anti-inflammatory agents.

Yucca aloifolia L. fruit (Yucca or Spanish bayonet, family Asparagaceae) is recognized for its purplish red color reflecting its anthocyanin content, which has a powerful antioxidant activity. This study aimed to investigate yucca (YA) fruit extract's protective effect on Parkinson's disease (PD). In vitro study, the anti-inflammatory activity of yucca fruit extracts was explored by measuring tumor necrosis factor receptor 2 (TNF-R2) and nuclear factor kappa B (NF-KB) to choose the most effective extract. Afterward, a detailed in vivo investigation of the protective effect of the most active extract on rotenone-induced PD was performed on male albino Wister rats. First, the safety of the extract in two different doses (50 and 100 mg/kg in 0.9% saline orally) was confirmed by a toxicological study. The rats were divided into four groups: 1) normal control (NC); 2) rotenone group; and third and fourth groups received 50 and 100 mg/kg yucca extract, respectively. The neurobehavioral and locomotor activities of the rats were tested by rotarod, open field, and forced swim tests. Striatal dopamine, renal and liver functions, and oxidative stress markers were assessed. Western blot analysis of brain tissue samples was performed for p-AMPK, Wnt3a, and β-catenin. Histopathological examination of striatal tissue samples was performed by light and electron microscopy (EM). The metabolites of the active extract were characterized using high-resolution LC-MS/MS, and the results showed the prevalence of anthocyanins, saponins, phenolics, and choline. Biochemical and histopathological tests revealed a dose-dependent improvement with oral Yucca extract. The current study suggests a possible neuroprotective effect of the acidified 50% ethanol extract (YA-C) of the edible Yucca fruit, making it a promising therapeutic target for PD.

Background and objectives: Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from Viscum schimperi (Loranthaceae), against TAA (thioacetamide)-produced acute hepatic and renal damage was explored. Materials and Methods: Mice were treated with OA for 7 days before TAA (200 mg/kg, i.p.). Serum indices of hepatorenal injury, pathological lesions, molecular biological indexes, and inflammatory/apoptotic genes were estimated. Results: The tissues of both organs were greatly affected by the TAA injection. That was evident through increased serum markers of hepato-renal injury as well as remarkable histopathological lesions. TAA-induced injury was associated with oxidative and inflammatory responses in both organs as there was an elevation of oxidative stress parameters (4-HNE (4-hydroxy-nonenal), MDA (malondialdehyde), NOx (nitric oxide)), decline of antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC)), and an increase in the gene expression/level of inflammatory mediators (interleukins (1β&6)). The inflammatory response was linked to a significant activation of NF-κB (nuclear-factor kappa-B)/TNF-α (tumor-necrosis factor-alpha) signaling. The inflammatory response in both organs was accompanied by apoptotic changes, including a rise in the gene expression and level of apoptotic parameters (caspase-3 and Bax) along with a decline in Bcl-2 (anti-apoptotic parameter) gene expression and level. These pathogenic events were found to be closely related to the suppression of the antioxidant signaling pathway, Nrf2 (nuclear-factor erythroid 2–related factor-2)/SIRT1 (sirtuin-1)/HO-1 (heme-oxygenase 1). On the other hand, OA significantly ameliorated TAA-induced injury in both organs. On the other hand, OA counterpoised the inflammatory response as it ameliorated NF-κB/TNF-α signaling and cytokine release. OA enhanced Nrf2/SIRT1/HO-1 signaling and counteracted apoptotic damage. Conclusions: OA showed anti-inflammation and antiapoptotic capacities that effectively suppressed TAA-induced acute hepatorenal damage.

Plants of the genus Echinop (Asteraceae) are traditional medicinal plants used to treat several GIT ailments, owing to their diverse bioactive secondary metabolites, including sesquiterpenoids, triterpenoids, phytosterols, phenolics, flavonoids, alkaloids, and essential oils. Echinops erinaceus Kit Tan is a wild perennial herb of the genus Echinops which is endemic to Oman, Saudi Arabia, and Yemen. Currently, there are no previous reports exploring its anti-ulcer and anti-inflammatory effects. Additionally, few reports have described the chemical profile of E. erinaceus Kit Tan. In the current study, the CHCl3 fraction of the aerial parts of the plant was subjected to chromatographic isolation and spectroscopic identification via 1D and 2D NMR, and MS. The plant afforded two new compounds, designated erinaceolic acid (E3) and erinaceoside (E5), in addition to five known compounds, namely taraxasterol acetate (E1), taraxasterol (E2), apigenin (E4), stigmasterol-3-O-β-D-glucoside (E6), and speranskoside (E7). The evaluation of the gastric ulcer protective activity of the total extract and successive fractions of E. erinaceus, using the in vivo ethanol-induced ulcer in rats model, revealed the significant effect of the tested extracts and fractions on the percentage of gastric ulcer protection and ulcer index (500 mg/kg) compared to antodine (20 mg/kg). The tested extracts and fractions also reduced the stomach contents of TNF-α and reduced IL-6 as compared to the untreated group. Histopathological examination of the gastric mucosal tissues of rats supportedprevious results. In addition, the main subfractions and their isolates were assessed for their in vitro anti-inflammatory activity against COX-2 and 15-LOX enzymes. The new compounds erinaceolic acid (E3) and speranskoside (E7) exhibited strong inhibition against COX-2 (3.41 and 2.62 µg/mL) and 15-LOX (10.05 and 5.51 µg/mL), respectively. A molecular docking study was performed to reveal the binding interaction modes of the most active compounds against the binding sites of COX-2 (PDB ID 3LN1) and 15-LOX (PDB ID 1LOX) proteins. Speranskoside (E7) showed a dual binding affinity better than that of the cocrystallized references, celecoxib and (2E)-3-(2-oct-1-yn-1-ylphenyl)acrylic acid (RS7) against both enzymes. This study shed a light on the potential use of E. erinaceus in the protection and treatment of gastric ulcers.

Red onion wastes (ROW) are valuable sources of bioactive metabolites with promising antimicrobial effects. Methicillin-resistant Staphylococcus aureus (MRSA) infections are a growing risk in hospitals and communities. This study aims to investigate the in vitro and in vivo antibiofilm activities of the acidified ethanolic extract of red onion scales (RO-T) and its fractions against an MRSA vaginal colonization model. The RO-T extract, as well as its anthocyanin-rich fraction (RO-P) and flavonoid-rich fraction (RO-S), recorded a promising antibacterial activity against highly virulent strains of bacteria (MRSA, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa). RO-S showed the highest antibacterial activity (MBC of 0.33 ± 0.11 mg/mL) against MRSA USA300 and significantly eradicated its biofilm formation with an IC50 of 0.003. Using a rat model, in vivo assessment on all samples, which were formulated as a hydrogel, revealed a significant reduction of MRSA bacterial load recovered from an infected vagina compared to that of the negative control group (NCG). RO-T extract and vancomycin groups recorded the highest antibacterial activity with a bacterial load 2.998 and 3.358 logs lower than the NCG, respectively. The histopathological investigation confirmed our findings. RO-T and RO-S were standardized for their quercetin content. Finally, ROW offers a new potent antibiofilm agent mostly due to its high quercetin content.

Wild plants are used by many cultures for the treatment of diverse ailments. However, they are formed from mixtures of many wanted and unwanted phytochemicals. Thus, there is a necessity to separate the bioactive compounds responsible for their biological activity. In this study, the chemical composition as well as antimicrobial and cytotoxic activities of Echinops erinaceus Kit Tan (Asteraceae) were investigated. This led to the isolation and identification of seven compounds, two of which are new (erinaceosin C3 and erinaceol C5), in addition to methyl oleate (C1) and ethyl oleate (C2), loliolide (C4), (E)-p-coumaric acid (C6), and 5,7,3`,5`-tetrahydroxy flavanone (C7). The structures of the isolated compounds were elucidated by 1D, 2D NMR, and HR-ESI-MS. The methanol extract showed the highest antimicrobial activity among the tested extracts and fractions. The n-hexane and EtOAc extracts showed remarkable antimicrobial activity against B. subtilus, P. aeruginosa, E. coli, and C. albicans. A cytotoxicity-guided fractionation of the most bioactive chloroform extract resulted in the isolation of bioactive compounds C1/C2, which showed significant cytotoxicity against HCT-116 and CACO2 cell lines (IC50 24.95 and 19.74 µg/mL, respectively), followed by compounds C3 (IC50 82.82 and 76.70 µg/mL) and C5 (IC50 99.09 and 87.27 µg/mL), respectively. The antioxidant activity of the bioactive chloroform fractions was screened. Molecular docking was used to explain the results of the antimicrobial and anticancer activities against five protein targets, including DNA gyrase topoisomerase II, enoyl-acyl carrier protein reductase of S. aureus (FabI), dihydrofolate reductase (DHFR), β-catenin, and human P-glycoprotein (P-gp).

Our study has renewed interest in the genus Jasmine for the treatment of chronic inflammatory conditions. Aerial parts of Jasminum grandiflorum L. subsp. floribundum total methanolic extract (JTME) were tested for its therapeutic potential as an anti-inflammatory agent using two experimental models in rats; acetic acid (AA) induced ulcerative colitis and adjuvant induced arthritis.The administration of JTME showed anti-inflammatory activity in a dose dependent manner. JTME, 400 mg/kg was like prednisolone, 2 mg/kg p.o. (the reference drug), since it improved the tissues of the colon clinically, macro and microscopically (ulcer index), and histopathological (scoring). It reduced the intestinal expression of pro-inflammatory cytokines in the colonic mucosa; IFNγ, TNFα, IL-6, IL-1, and MPO. It also preserved tight junctions in intestinal epithelial cells by counter-regulating claudin-5 and occludin levels additionally, it had a potent antioxidant activity. The expressions of NF-κB p65, TNF-α and caspase-3 in rats administered AA (2 mL of 4% solution, once, intrarectally) were significantly increased, where the lowest expression was scored in JTME, 400 mg/kg group. In the adjuvant induced model of rheumatoid arthritis, the TJME, 400 mg/kg reduced the levels of cathepsin D, iNOS, NO, RF, CRP, CPP and elevated the total antioxidant capacity of tissues. Additionally, it maintained bones without histopathological lesions, articular cartilage damage, and inflammation of the synovial membrane and periarticular tissues, in contrast to arthritic rats. Finally, we report a new detailed study to validate the medicinal importance of Jasminum for the chronic inflammatory disorders with immune dysfunction with anti-inflammatory and antioxidant effects.

Context: Genus Verbascum (Scrophulariaceae) comprises about 360 species of flowering plants. Verbascum has been used in traditional medicine as an astringent, antitussive, analgesic and anti-inflammatory. Objective: Nothing was found in the available literature concerning Verbascum nubicum Murb; therefore, the study evaluates the biological activities, isolated compounds and HPLC profile. Materials and methods: Methanol extract (VME) and butanol fraction (VBF) of air-dried powdered V. nubicum were obtained. Four compounds were isolated from VBE and identified by 1H- and 13C-NMR. High-performance liquid chromatography (HPLC) profile was determined for (VME). LD50, in vitro antioxidant, in vivo antiulcerogenic and anti-inflammatory activities as well as hepatoprotective activity were assessed. Anti-ulcerogenic and hepatoprotective activities were supported by histopathological examinations. Results: HPLC analysis of VME revealed the presence of luteolin 7-glucoside (2215.43 mg/100 g), hesperidin (954.51 mg/100 g) and apigenin (233.15 mg/100 g) as major compounds. Four compounds were isolated and confirmed by NMR data, were identified as gentiopicroside, luteolin, aucubin and gallic acid. The LD50 of VME and VBF extracts were calculated to be 8200 and 4225 mg/kg b.w., respectively. IC50 values of VBE and VMF as measured by DPPH·method were 43.6 and 50 µg/mL, respectively. Also, anti-inflammatory effect of VME (400 mg/kg b.w.) and VBF (200 mg/kg b.w.) induced edema model after 120 min were 61.93 and 56.13%, respectively. Antiulcerogenic activity of VME (400 mg/kg b.w.) and VBF (200 mg/kg b.w.) in albino rats were 65.14 and 84.57%, respectively. Conclusions: The V. nubicum extracts displayed safe and promising antioxidant, anti-inflammatory and hepatoprotective properties. It can be also applied in the pharmacy industry, food industry and healthcare.

Root and bark of Limonium axillare (Forssk) Kuntze are used as antidiabetic remedies in parts of East Africa, but this activity has never been fully investigated. To validate its ethnobotanical use, we compared the chemical and pharmacological profiles of the ethanolic extracts of L. axillare root (REE) and aerial parts (AEE). Administration of REE (500 mg kg-1) reduced streptozotocin-induced hyperglycemia by 44%, restored serum insulin levels, reestablished Glut2 and Glut4 expression and ameliorated pancreatic tissue damage in diabetic rats. In vitro studies revealed a strong radical scavenging effect, α-glucosidase, and α-amylase inhibition activity of REE at IC50 at 25.2, 44.8 and 89.1μg/mL, respectively. HPLC analysis identified ten phenolic compounds in REE with umbelliferone as the major constituents at 10 ± 0.081 mg/g of extract. Additionally, six compounds were isolated from REE including, β-sitosterol-3-palmitate, β-sitosterol, myricetin and gallic acids with two new tetrahydrofuran monoterpenes; 2-isopropyl- 3,4,4, trimethyl-tetrahydrofuran (3), and 2-isopropyl-4-methyl-tetrahydrofuran-3,4 dicarboxylic acid (4), the latter was revealed by molecular docking to be a good ligand to glycerol-3-phosphate dehydrogenase a key enzyme in glycolysis.

Hibiscus sabdariffa L. (Malvaceae) is one of the well-known traditionally used remedy worldwide. It exhibited numerous pharmacological properties including antioxidant, antidepressant, sedative, anti-inflammatory, antiproliferative, antimicrobial and neuroprotective activities. The aim of this study is to highlight the mechanisms underlying the neuroprotective effects of anthocyanin-enriched extracts of two Hibiscus varieties (white and red calyces) in the management of Alzheimer’s disease (AD) in addition to their metabolic profiling. The anthocyanin contents were determined quantitatively using the pH-differential technique and qualitatively by LC/MS/MS. The extracts were tested in vitro for their antioxidant potential as well as acetylcholinesterase inhibition activity and both showed promising activities. The LC/MS/MS analysis allowed the tentative identification of 26 and 24 metabolites in red and white calyces, respectively, represented by anthocyanins, flavonoids, aliphatic and phenolic acids. In vivo, streptozotocin induced AD in mice model was established and Hibiscus extracts were tested at a dose of 200 mg kg−1 compared to celecoxib (30 mg/kg). Histopathology of cerebral cortex and hippocampus, immunohistochemistry for tau- protein and caspase-3 with behavioral tests and measurement of several biochemical parameters were done. Hibiscus prevented memory impairment, and this could be attributed to the amelioration of STZ-induced neuroinflammation and amyloidogenesis. Consequently, Hibiscus represents a promising safe agent that can be repurposed for AD through exerting anti-inflammatory, anti-acetylcholinesterase, antioxidant, and anti-amyloidogenic activities.

Diabetes of type 2 is a worldwide epidemic disease of global prevalence. Caralluma quadrangula is wild Saudi plant used by traditional healers as antidiabetic, in case of hunger, and many other diseases. Nothing was reported to justify the use of the plant in case of diabetes. The plant material was extracted with water and with methanol, the methanol fraction was further fractionated into chloroform, n-butanol, in addition to the remaining mother liquor. The water and methanolic extracts as well as different methanolic fractions were evaluated in STZ-induced diabetic rats for their antihyperglycaemic activity. The results showed a significant decrease in fasting blood glucose levels in diabetic treated rats after the administration of most of the extracts and fractions of C. quadrangula and glibenclamide. The most potent activity was shown by administration of the methanolic extract (200 mg/kg), chloroform, n-butanol fraction at dose of 100 mg/kg, as well as the major pregnane glycoside russelioside B isolated from C. quadrangula. In conclusion, this study proved the traditional use of C. quadrangula in diabetes mellitus. Keywords: Asclepiadaceae, Caralluma quadrangula, Antihyperglycemic, Fast blood glucose, G-6-Pase, Insulin

Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDRAB) present a serious challenge because of their capability to cause biofilm resistance to commonly used antibiotics producing chronic infections and hindering the process of wound healing. In the current study, we investigated the antibacterial activity of Caralluma quadrangula extracts (MeOH, and its fractions CH2Cl2 and n-butanol) against multidrug-resistant MRSA USA300 and A. baumannii AB5057. In vitro, the MeOH extract and both fractions of C. quadrangula significantly inhibited biofilm formation and disrupted previously established biofilm by MRSA and MDRAB at all the tested concentrations (0.625, 0.313, and 0.156 mg/mL). In vivo, C. quadrangula extracts successfully decreased bacterial loads in MRSA-infected skin lesions in mice. Four pregnane glycosides and one flavone glycoside were isolated from the bioactive n-butanol fraction. The isolated compounds (Rus A–E) were tested for their biofilm inhibition and biofilm detachment activities. The results revealed that Rus C was the most active compound (IC50 = 0.139 mmole), while Rus E was the least active (IC50 = 0.818 mmole). These results support the potential use of C. quadrangula extracts or their isolated compounds for hindering the biofilm attachment and the virulence of MRSA and MDRAB and their application as a topical antimicrobial preparation for MRSA skin infections.

Sesame (Sesamum indicum L.) is a global oil crop. Sesame oil has been regarded as functional oil with antioxidant properties in several in vivo studies but little is known about its minor fraction. In this line, this study figures out the profile of the polar fraction of Egyptian cultivar Giza 32 sesame oil (SG32 oil) employing reversed-phase high-performance liquid chromatography coupled with diode array detection and electrospray ionization-quadrupole-time-of-flight-mass spectrometry and tandem MS. The characterization of the sesame oil metabolites depended on the observation of their retention time values, accurate MS, and MS/MS data, with UV spectra, and compared with relevant literature and available standards. Remarkably, 86 metabolites were characterized and sub-grouped into phenolic acids, lignans, flavonoids, nitrogenous compounds, and organic acids. From the characterized metabolites, 72 compounds were previously characterized in SG32 cake, which presented antioxidant properties, and hence it could contribute to SG32 oil antioxidant properties. Further studies are required to state the presence of such phenolics in commercial sesame oils and what of these compounds resist oil refining.

Phyllanthin and related lignans were found to be responsible, at least in part, for most of the activity of Phyllanthus species. This observation encouraged the authors to develop methods for the preparation of an extract rich in phyllanthin and related lignans from the aerial parts of P. niruri L. Direct extraction with solvents produced extracts with variable yields and contents of lignans. Lignans were identified by LC-ESI-MS analysis as phyllanthin (used as marker substance), hypophyllanthin, phylltetralin, nirtetralin, and niranthin. Extraction with boiling water produced 18.10 g% (w/w) extract with a trace amount of lignans (phyllanthin content of 0.33 ± 0.10 mg/g extract), while extraction with MeOH gave 3.6 g% w/w extract with a low phyllanthin content (3.1 mg/g extract), as determined by HPLC. However, Soxhlet extraction with hexane, CH2Cl2, or acetone gave extracts with low yields (0.82, 1.12, and 3.40 g% w/w, respectively) and a higher phyllanthin contents (36.2 ± 2.6, 11.7 ± 1.68, and 11.7 ± 1.10 mg/g extract, respectively). Extraction quality and efficiency were optimized by adopting the following three different approaches: (1) Alkaline digestion of the plant material with 30% potassium hydroxide yielded 3.1 g% w/w of purified extract with high phyllanthin content (22.34 ± 0.13 mg/g); (2) microwave-assisted extraction using 80% MeOH gave an extract with a better yield (8.13 g% w/w) and phyllanthin content (21.2 ± 1.30 mg/g) (after filtration through a Diaion HP-20 column); and (3) treatment of the ground plant material at 50 °C with two hydrolytic enzymes, cellulase (9 U/g for 12 h) and then, protease (4 U/g up to 72 h) optimized the yield of extract (13.92 g% w/w) and phyllanthin content (25.9 mg/g extract and total lignans content of 85.87 mg/g extract). In conclusion, the nonconventional methods presented here are superior for optimizing the yield of extract and its lignan contents from the aerial parts of P. niruri.

Background and purpose: Russelioside B (RB) is a pregnane glycoside obtained from Caralluma quadrangula; a herb with antidiabetic, anti-inflammatory, and antihyperlipidemic activities. The present experiment tested the possible role of RB in controlling weight gain in rats fed on high fat (HF) diet.Methods: RB was separated from the n-butanol fraction of the crude methanolic extract by chromatographic separation on a Si gel column according to the procedures described previously. The experiment of the biological assessment of RB used 32 male Wistar rats (4 groups, n = 8). Group 1 rats were fed with a palatable normal diet. Group 2, 3, and 4 were fed on HF diet for 16 weeks. Group 2 served as the HF diet control group while Group 3 and 4 received daily oral doses of RB (25 and 50 mg/kg) during the last four weeks. Animals’ parameters like weight gain, fasting level of blood sugar, serum lipids, and serum liver enzyme activities were measured. Liver or adipose tissue weight was divided by the rat’s body weight and multiplied by 100 to obtain the liver or adipose tissue index, respectively. Adipose tissues were processed for histopathological examination, measurement of mRNA expression of visfatin, leptin, adiponectin, uncoupling protein-1 (UCP-1), and carnitine palmitoyl transferase-1 (CPT-1). Furthermore, serum levels of insulin, interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), leptin, resistin, and adiponectin were assessed using ELISA kits.Results: Rats fed with the HF diet exhibited significant body weight gain, abnormal liver function, disturbed lipid profile, and greater serum level of pro-inflammatory cytokines in addition to greater insulin resistance, adipose tissue and liver indices. Further, rats fed with the HF diet displayed upregulations in the expression of visfatin and leptin with downregulations in the expression of adiponectin, UCP-1, and CPT-1 compared to normal rats. Interestingly, RB (25 or 50 mg/kg) favorably modulated the measured parameters.Conclusion: Data from this study documented the beneficial role of RB in diminishing weight gain, improving the inflammatory perturbations and energy expenditure in HF diet fed rats. Therefore, RB might be a promising candidate for obesity.

The antihyperglycemic and antihyperlipidemic effects of the methanolic extracts of the aerial parts of Cleome ramosissima Parl. (Cleomaceae), Barleria bispinosa (Forssk.) Vahl. (Acanthaceae) and Tribulus macropterus Boiss. (Zygophyllaceae) were evaluated in streptozotocin (STZ) induced diabetic rats at a dose of 500 mg/kg bw. The reduction in fasting blood glucose level (BGL) was observed in the following order C. ramosissima, B. bispinosa and T. macropterus at the 4th week of administration. C. ramosissima and T. macropterus also showed significant increase in plasma insulin by 100.6% and 189.9%, respectively. The studied plant extracts induced an increase in both utilization and tolerance of glucose in diabetic rats. The hypolipidemic effect of C. ramosissima and T. macropterus was demonstrated by a significant reduction in plasma total cholesterol (TC) (42.6% and 37.2%, respectively) and low density lipoprotein cholesterol (LDL-C) (48.0% and 42.1%, respectively) and the increase of high density lipoprotein cholesterol (HDL-C) by 81.0% and 91.9%, respectively. B. bispinosa decreased the blood levels of LDL-C and increased the levels of HDL-C, while it did not affect the TC blood levels. The present data suggest that C. ramosissima and T. macropterus have both antihyperglycemic and hypolipidemic effects with high insulin-secreting activity.

Agri-food residues represent a rich source of nutrients and bioactive secondary metabolites, including phenolic compounds. The effective utilization of these by-products in food supplements and the nutraceuticals industry could provide a way of valorization in the transition to becoming more sustainable. In this context, the present study describes the phenolic profiling of sesame (Sesamum indicum L.) cake using reversed-phase high-performance liquid chromatography coupled to diode array detection and quadrupole-time-of-flight-mass spectrometry. Compounds were characterized based on their retention time, UV spectra, accurate mass spectrometry (MS) and MS/MS data along with comparison with standards, whenever possible, and the relevant literature. The characterized compounds (112 metabolites) belong to several classes, namely, phenolic acids (hydroxybenzoic acids and hydroxycinnamic acids), flavonoids, and lignans. Moreover, organic acids and some nitrogenous compounds were characterized. The total phenol content and the antioxidant activity of the cake extract were determined. This study provides useful information for the valorization of by-products from the sesame oil industry.

Cardiotoxicity is one of the major side effects of anthracycline antibiotics. Most studies implicated increased oxidative stress as the major determinant of doxorubicin (DOX) cardiotoxicity. The aim of the current investigation was to study the possible cardioprotective effect of Stachys schimperi Vatke (family Lamiaceae) on DOX-induced cardiotoxicity in rats based on biochemical and histopathological parameters. The phenolic profile of the methanol extract was determined qualitatively by HPLC. Isoscutellarein 7-O-[2″-O-(6″′-acetyl)-β-d-allopyranosyl]-β-d-glucopyranoside (compound 1) was isolated and identified from EB fraction as a major constituent for the first time from this Stachys species. The methanolic extract and the combined EtOAc and n-butanol fractions (EB) as well as compound 1 showed prominent free radical scavenging activity when assessed by the DPPH method. The methanolic extract showed moderate protection against DOX-induced alteration in cardiac oxidative stress markers; GSH and MDA, and cardiac serum markers; CK-MB and LDH activities. Additionally, histopathological study denoted mild protection against DOX-induced cardiotoxicity. It was concluded that Stachys schimperi Vatke methanolic extract protected against DOX-induced cardiotoxicity, at least in part, by virtue of its antioxidant activity.