Phytochemical profiling of Salsola tetragona Delile by LC-HR/MS and investigation of the antioxidant, anti-inflammatory, cytotoxic, antibacterial and anti-SARS-CoV-2 activities.

This study aimed to investigate the phytochemical composition and biological activity of Salsola tetragona Delile. (Amaranthaceae), a medicinal plant. The study evaluated the antioxidant potential of the crude extract and five fractions of S. tetragona using DPPH•, ABTS•+, CUPRAC, and metal chelating assays. The anti-inflammatory activity was determined using a protein denaturation assay, and the antibacterial activity was determined by the Minimum inhibitory concentrations (MICs) for the growth of Escherichia coli and Staphylococcus aureus strains. The MTT test and an in vitro scratch assay evaluated the effects on cell viability and cell migration. The potential anti-SARS-CoV-2 activity was assessed by analyzing the effects on the interaction between ACE2 and Spike protein. The bioactive compounds present in the plant were identified using LC-HR/MS analysis. The crude hydromethanolic extract (STM) and five fractions of S. tetragona, n-hexane (STH), dichloromethane (STD), ethyl acetate (STE), n-butanol (STB), and aqueous (STW) showed significant antioxidant activity in four different tests. In the anti-inflammatory assay, the ethyl acetate fraction exhibited significantly higher activity than Aspirin® (IC50 = 13 ± 5 µg/mL). The crude extract and its fractions showed positive antibacterial activity with similar MICs. In the cytotoxicity assay against the breast cancer cell line MCF7, the dichloromethane fractions (STD) were very effective and demonstrated superiority over the other fractions (IC50 = 98 µg/mL). Moreover, the potential of the extract and fractions as anti-SARS-CoV-2, the ethyl acetate, and dichloromethane fractions demonstrated important activity in this test. LC-HR/MS analysis identified 16 different phenolic compounds, Eleven of which had not been previously reported in the genus Salsola. The results suggest that the extracts of S. tetragona have the potential to become new sources for developing plant-based therapies for managing a range of diseases.

Microbial Transformation of the Sesquiterpene Lactone, Vulgarin, by Aspergillus niger.

The biotransformation of vulgarin (1), an eudesmanolides-type sesquiterpene lactone obtained from Artemisia judaica, by the microorganism, Aspergillus niger, was carried out to give three more polar metabolites; 1-epi-tetrahydrovulgarin (1α,4α-dihydroxy-5αH,6,11ßH-eudesman-6,12-olide (2), 20% yield, 1α,4α-dihydroxyeudesm-2-en-5αH,6,11ßH-6,12-olide (3a), 10% yield, and C-1 epimeric mixture (3a, b), 4% yield, in a ratio of 4:1, 3a/3b. The structures of vulgarin and its metabolites were elucidated by 1 and 2D NMR spectroscopy in conjunction with HRESIMS. Metabolites (3a) and (3b) are epimers, and they are reported here for the first time as new metabolites obtained by biotransformation by selective reduction at C-1. Vulgarin and its metabolites were evaluated as anti-inflammatory agents using the human cyclooxygenase (COX) inhibitory assay. The obtained data showed that (1) exhibited a good preferential inhibitory activity towards COX-2 (IC50 = 07.21 ± 0.10) and had a moderate effect on COX-1 (IC50 = 11.32 ± 0.24). Meanwhile, its metabolite (3a) retained a selective inhibitory activity against COX-1 (IC50 = 15.70 ± 0.51). In conclusion, the results of this study revealed the necessity of the presence α, ß unsaturated carbonyl group in (1) for better COX-2 inhibitory activity. On the other hand, the selectivity of (1) as COX-1 inhibitor may be enhanced via the reduction of C-1 carbonyl group.

Biochemical Profile and In Vitro Therapeutic Properties of Two Euhalophytes, Halocnemum strobilaceum Pall. and Suaeda fruticosa (L.) Forske., Grown in the Sabkha Ecosystem in the Algerian Sahara.

This study reports the biochemical profile and in vitro biological activities of the aerial part of two shrubs: Halocnemum strobilaceum and Suaeda fruticosa, a halophytes species native to saline habitats. The biomass was evaluated by determining its physiological properties and approximate composition. Hydro-methanolic extracts from Halocnemum strobilaceum and Suaeda fruticosa have been investigated for the inhibition of bacterial growth, the protection of proteins (albumin) from denaturation, and cytotoxicity to hepatocellular carcinomas (Huh-7 and HepG2). Their antioxidant activity was evaluated by five tests, including one that examined their ability to inhibit hydrogen peroxide (H2O2)-induced hemolysis. The profile of their phenolic compounds was also determined. These two euhalophytes had a high moisture content, high levels of photosynthetic pigments, elevated levels of ash and protein, low oxidative damage indices, MDA (Malondialdehyde) and proline, and low lipids levels. Their content was also characterized by a moderate acidity with good electrical conductivity. They contained abundant levels of phytochemicals and varied phenolic contents. Reverse phase high performance liquid chromatography (RP-HPLC) analysis revealed the presence of caffeic acid, p-coumaric acid, rutin, and quercetin in both plant extracts. On the pharmaceutical level, the two euhalophytes had anti-inflammatory, antibacterial, antioxidant, and cytotoxic properties, and therefore it was recommended to isolate and identify biologically active compounds from these plants and evaluate them in vivo.

Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression.

The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the ß-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.

Comparative Cytotoxic Evaluation of Zygophyllum album Root and Aerial Parts of Different Extracts and Their Biosynthesized Silver Nanoparticles on Lung A549 and Prostate PC-3 Cancer Cell Lines.

The current work demonstrates a comparative study between aerial and root parts of Zygophyllum album L. The total phenolic (TPC) and flavonoid content (TFC), in addition to the antioxidant activity, of the crude extracts were investigated, where the aerial parts revealed a higher value overall. By means of UV-VIS and HPLC, rutin and caffeic acid were detected and then quantified as 5.91 and 0.97 mg/g of the plant extract, respectively. Moreover, the biosynthesis of AgNPs utilizing the crude extract of the arial parts and root of Z. album L. and the phenolic extracts was achieved in an attempt to enhance the cytotoxicity of the different plant extracts. The prepared AgNPs formulations were characterized by TEM and zeta potential measurements, which revealed that all of the formulated AgNPs were of a small particle diameter and were highly stable. The mean hydrodynamic particle size ranged from 67.11 to 80.04 nm, while the zeta potential ranged from 29.1 to 38.6 mV. Upon biosynthesis of the AgNPs using the extracts, the cytotoxicity of the tested samples was improved, so the polyphenolics AgNPs of the aerial parts exhibited a potent cytotoxicity against lung A549 and prostate PC-3 cancer cells with IC50 values of 6.1 and 4.36 µg/mL, respectively, compared with Doxorubicin (IC50 values of 6.19 and 5.13 µg/mL, respectively). Regarding the apoptotic activity, polyphenolics AgNPs of the aerial parts induced apoptotic cell death by 4.2-fold in PC-3 and 4.7-fold in A549 cells compared with the untreated control. The mechanism of apoptosis in both cancerous cells appeared to be via the upregulation proapoptotic genes; p53, Bax, caspase 3, 8, and 9, and the downregulation of antiapoptotic gene, Bcl-2. Hence, this formula may serve as a good source for anticancer agents against PC-3 and A549 cells.

Silver Nanoparticles Formulation of Flower Head's Polyphenols of Cynara scolymus L.: A Promising Candidate against Prostate (PC-3) Cancer Cell Line through Apoptosis Activation.

Cynara scolymus L. (Family: Compositae) or artichoke is a nutritious edible plant widely used for its hepatoprotective effect. Crude extracts of flower, bract, and stem were prepared and evaluated for their in vitro antioxidant activity and phenolic content. The flower crude extract exhibited the highest phenolic content (74.29 mg GAE/gm) as well as the best in vitro antioxidant activity using total antioxidant capacity (TAC), ferric reducing antioxidant power (FEAP), and 1,1-diphenyl-2-picrylhyazyl (DPPH) scavenging assays compared with ascorbic acid. Phenolic fractions of the crude extracts of different parts were separated and identified using high-performance liquid chromatography HPLC-DAD analysis. The silver nanoparticles of these phenolic fractions were established and tested for their cytotoxicity and apoptotic activity. Results showed that silver nanoparticles of a polyphenolic fraction of flower extract (Nano-TP/Flowers) exhibited potent cytotoxicity against prostate (PC-3) and lung (A549) cancer cell lines with IC50 values of 0.85 µg/mL and 0.94 µg/mL, respectively, compared with doxorubicin as a standard. For apoptosis-induction, Nano-TP/Flowers exhibited apoptosis in PC-3 with a higher ratio than in A549 cells. It induced total prostate apoptotic cell death by 227-fold change while it induced apoptosis in A549 cells by 15.6-fold change. Nano-TP/Flowers upregulated both pro-apoptotic markers and downregulated the antiapoptotic genes using RT-PCR. Hence, this extract may serve as a promising source for anti-prostate cancer candidates.

Zygo-Albuside A: New Saponin from Zygophyllum album L. with Significant Antioxidant, Anti-Inflammatory and Antiapoptotic Effects against Methotrexate-Induced Testicular Damage.

Chemical investigation of the crude extract of the aerial part of Zygophyllum album L. (Z. album) led to the isolation of a new saponin, Zygo-albuside A (7), together with seven known compounds, one of them (caffeic acid, compound 4) is reported in the genus for the first time. NMR (1D and 2D) and mass spectrometric analysis, including high-resolution mass spectrometry (HRMS), were utilized to set up the chemical structures of these compounds. The present biological study aimed to investigate the protective antioxidant, anti-inflammatory, and antiapoptotic activities of the crude extract from the aerial part of Z. album and two of its isolated compounds, rutin and the new saponin zygo-albuside A, against methotrexate (MTX)-induced testicular injury, considering the role of miRNA-29a. In all groups except for the normal control group, which received a mixture of distilled water and DMSO (2:1) as vehicle orally every day for ten days, testicular damage was induced on the fifth day by intraperitoneal administration of MTX at a single dose of 20 mg/kg. Histopathological examination showed that pre-treatment with the crude extract of Z. album, zygo-albuside A, or rutin reversed the testicular damage induced by MTX. In addition, biochemical analysis in the protected groups showed a decrease in malondialdehyde (MDA), interleukin-6 (IL-6) and IL-1ß, Bcl-2-associated-protein (Bax), and an increase in B-cell lymphoma 2 (Bcl-2) protein, catalase (CAT), superoxide dismutase (SOD) in the testis, along with an increase in serum testosterone levels compared with the unprotected (positive control) group. The mRNA expression levels of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), p53, and miRNA-29a were downregulated in the testicular tissues of the protected groups compared with the unprotected group. In conclusion, the study provides sufficient evidence that Z. album extract, and its isolated compounds, zygo-albuside A and rutin, could alleviate testicular damage caused by the chemotherapeutic agent MTX.

Chemical profiling, cytotoxic activities through apoptosis induction in MCF-7 cells and molecular docking of Phyllostachys heterocycla bark nonpolar extract.

The chemical constituents of the nonpolar fractions of the bamboo shoot skin Phyllostachys heterocycla were extensively studied. The phytochemical study was divided into two parts: the first deals with isolation of the chemical constituents using different chromatographic techniques that resulted in isolation of four compounds. The chemical structures of the pure isolated compounds were elucidated using different spectroscopic data. The second part deals with identification of the rest of the constituents using the GC technique. Additionally, both crude extract and the pure isolated compounds were investigated for cytotoxic activity. One of the isolated compounds; namely glyceryl 1-monopalmitate showed highly promising effect against the MCF-7 cells with (IC50 = 19.78 µM) compared to 5-FU (26.98 µM), and it remarkably stimulated apoptotic breast cancer cell death with 31.6-fold (16.13% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Moreover, the identified compounds especially 1 were found to have high binding affinity towards both TPK and VEGFR-2 through the molecular docking studies which highlight its mode of action. HighlightsChemical profiling of Phyllostachys heterocycla bark nonpolar extract was fully identified.Glyceryl 1-monopalmitate showed highly promising effect against the MCF-7 cells with (IC50 = 19.78 µM) compared to 5-FU (26.98 µM).Glyceryl 1-monopalmitate significantly stimulated apoptotic breast cancer cell death with 31.6-fold by arresting cell cycle at G2/M and preG1 phases.Molecular docking simulation showed good binding affinities towards TPK and VEGFR-2 proteins.Communicated by Ramaswamy H. Sarma.

Plicosepalus acacia Extract and Its Major Constituents, Methyl Gallate and Quercetin, Potentiate Therapeutic Angiogenesis in Diabetic Hind Limb Ischemia: HPTLC Quantification and LC-MS/MS Metabolic Profiling.

Plicosepalus acacia (Fam. Loranthaceae) has been reported to possess hypoglycemic, antioxidant, antimicrobial, and anti-inflammatory effects. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis revealed the presence of a high content of polyphenolic compounds that are attributed to the therapeutic effects of the crude extract. In addition, methyl gallate and quercetin were detected as major phytomedicinal agents at concentrations of 1.7% and 0.062 g%, respectively, using high-performance thin layer chromatography (HPTLC). The present study investigated the effect of the P. acacia extract and its isolated compounds, methyl gallate and quercetin, on hind limb ischemia induced in type 1 diabetic rats. Histopathological examination revealed that treatment with P. acacia extract, methyl gallate, and quercetin decreased degenerative changes and inflammation in the ischemic muscle. Further biochemical assessment of the hind limb tissue showed decreased oxidative stress, increased levels of nitric oxide and endothelial nitric oxide synthase (eNOS), and enhancement of the levels of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) in the groups treated with methyl gallate and quercetin. Expression levels of hypoxia inducible factor-1 alpha (HIF-1α), VEGF, fibroblast growth factor-2 (FGF-2), and miR-146a were upregulated in the muscle tissue of methyl gallate- and quercetin-treated groups along with downregulation of nuclear factor kappa B (NF-κB). In conclusion, P. acacia extract and its isolated compounds, methyl gallate and quercetin, mediated therapeutic angiogenesis in diabetic hind limb ischemia.

Possible Synergistic Antidiabetic Effects of Quantified Artemisia judaica Extract and Glyburide in Streptozotocin-Induced Diabetic Rats via Restoration of PPAR-α mRNA Expression.

Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second-fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth-seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the ß-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy.

Phytochemical Analysis of Anvillea garcinii Leaves: Identification of Garcinamines F-H and Their Antiproliferative Activities.

Anvillea garcinii is a medicinal plant used in the Arab region for intestinal diseases, lung and liver diseases, digestive problems, and as an antidiabetic agent. Repeated chromatographic purifications of A. garcinii leaves led to the isolation of three undescribed guaiane sesquiterpene derivatives, named garcinamines F-H, characterized by the presence of an amino acid unit, along with five known sesquiterpene lactones (garcinamines B-E and 9ß-hydroxyparthenolide). The structures of the new compounds were established using spectroscopic (1D and 2D NMR) and spectrometric methods (ESIMS). Garcinamine H possesses a double bond at the Δ1,10 position, a structural feature rarely reported in guaianolide-type sesquiterpenes. The antiproliferative activity of the isolated sesquiterpenes was screened against three different cancer cell lines, and 9ß-hydroxyparthenolide and garcinamines C and D displayed significant effects against lung carcinoma (A549), colon carcinoma (LoVo), and breast carcinoma (MCF7) cell lines.

Chemical Constituent Profiling of Phyllostachys heterocycla var. Pubescens with Selective Cytotoxic Polar Fraction through EGFR Inhibition in HepG2 Cells.

Different extracts of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens were screened against panel of cancer cell lines and normal one. The cell viability results exhibited that the ethyl acetate extract showed the least vitality percentage of 2.14% of HepG2 cells. Accordingly, it was subjected to chromatographic separation, which resulted in the isolation of a new natural product; 7-hydroxy, 5-methoxy, methyl cinnamate (1), together with four known compounds. The structures of the pure isolated compounds were deduced based on different spectroscopic data. The new compound (1) was screened against the HepG2 and MCF-7 cells and showed IC50 values of 7.43 and 10.65 µM, respectively. It induced apoptotic cell death in HepG2 with total apoptotic cell death of 58.6% (12.44-fold) compared to 4.71% in control by arresting cell cycle progression at the G1 phase. Finally, compound 1 was validated as EGFR tyrosine kinase inhibitor in both enzymatic levels (IC50 = 98.65 nM compared to Erlotinib (IC50 = 78.65 nM). Finally, in silico studies of compound 1 through the molecular docking indicated its high binding affinity towards EGFR protein and the ADME pharmacokinetics indicated it as a drug-like.

Sterols and Triterpenes from Dobera glabra Growing in Saudi Arabia and Their Cytotoxic Activity.

A new lupane caffeoyl ester, lup-20(29)-ene 3ß-caffeate-30-al (7), and a new oleanane-type triterpene, 3ß-hydroxyolean-13(18)-en-12-one (17), were isolated from the aerial parts of Dobera glabra (Forssk), along with ten known triterpenes, including seven lupane-type lupeol (1), 30-nor-lup-3ß-ol-20-one (2), ∆1-lupenone (3), lup-20(29)-en-3ß,30-diol (4), lupeol caffeate (5), 30-hydroxy lup-20(29)-ene 3ß-caffeate (6), and betunaldehyde (8); three oleanane-type compounds were also identified, comprising δ-amyrone (15), δ-amyrin (16), and 11-oxo-ß-amyrin (18); together with six sterols, comprising ß-sitosterol (9), stigmasterol (10), 7α-hydroxy-ß-sitosterol (11), 7α-hydroxy-stigmasterol (12), 7-keto-ß-sitosterol (13), and 7-keto-stigmasterol (14). Their structures were elucidated using a variety of spectroscopic techniques, including 1D (1H, 13C, and DEPT-135 13C) and 2D (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC) nuclear magnetic resonance (NMR) and accurate mass spectroscopy. Subsequently, the different plant extracts and some of the isolated compounds (1-9, 11 and 13) were investigated for their possible cytotoxic activity in comparison to cisplatin against a wide array of aggressive cancer cell lines, such as colorectal cancer (HCT-116), hepatocellular carcinoma (HepG-2), and prostate cancer (PC-3) cell lines. Compound 11 displayed broad cytotoxicity against all of the tested cell lines (IC50 ≅ 8 µg/mL in all cases), and a high safety margin against normal Vero cells (IC50 = 70 µg/mL), suggesting that 11 may be a highly selective and effective anticancer agent candidate. Notably, the evidence indicated that the mode of action of compound 11 could possibly consist of the inhibition of phosphodiesterase I (80.2% enzyme inhibition observed at 2 µM compound concentration).

Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin Phyllostachys heterocycla var. pubescens.

Phytochemical screening of nonpolar fractions from the methanol extract of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens resulted in the isolation of a new sterol-glucoside-fatty acid derivative (6'-O-octadeca-8'',11''-dienoyl)-sitosterol-3-O-ß-d-glucoside (1), together with six known compounds. The chemical structures of the pure isolated compounds were deduced based on different spectral data. The isolated compounds were assessed to determine their cytotoxic activity, and the results were confirmed by determining their apoptotic activity. Compound 1 was more cytotoxic against the MCF-7 cells (IC50 = 25.8 µM) compared to Fluorouracil (5-FU) (26.98 µM), and it significantly stimulated apoptotic breast cancer cell death with 32.6-fold (16.63% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Additionally, RT-PCR results further confirmed the apoptotic activity of compound 1 by the upregulation of proapoptotic genes (P53; Bax; and caspases 3, 8, and 9) and downregulation of the antiapoptotic genes (BCL2). Finally, the identified compounds, especially 1, were found to have high binding affinity towards both tyrosine-specific protein kinase (TPK) and vascular endothelial growth factor receptor (VEGFR-2) through the molecular docking studies that highlight its mode of action.

Momordica charantia Extract Protects against Diabetes-Related Spermatogenic Dysfunction in Male Rats: Molecular and Biochemical Study.

More than 90% of diabetic patients suffer from sexual dysfunction, including diminished sperm count, sperm motility, and sperm viability, and low testosterone levels. The effects of Momordica charantia (MC) were studied by estimating the blood levels of insulin, glucose, glycosylated hemoglobin (HbA1c), testosterone (TST), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in diabetic rats treated with 250 and 500 mg/kg b.w. of the total extract. Testicular antioxidants, epididymal sperm characteristics, testicular histopathology, and lesion scoring were also investigated. Testicular mRNA expression of apoptosis-related markers such as antiapoptotic B-cell lymphoma-2 (Bcl-2) and proapoptotic Bcl-2-associated X protein (Bax) were evaluated by real-time PCR. Furthermore, caspase-3 protein expression was evaluated by immunohistochemistry. MC administration resulted in a significant reduction in blood glucose and HbA1c and marked elevation of serum levels of insulin, TST, and gonadotropins in diabetic rats. It induced a significant recovery of testicular antioxidant enzymes, improved histopathological changes of the testes, and decreased spermatogenic and Sertoli cell apoptosis. MC effectively inhibited testicular apoptosis, as evidenced by upregulation of Bcl-2 and downregulation of Bax and caspase-3. Moreover, reduction in apoptotic potential in MC-treated groups was confirmed by reduction in the Bax/Bcl-2 mRNA expression ratio.

Antibacterial and Antifungal Sesquiterpenoids from Aerial Parts of Anvillea garcinii.

Two new sesquiterpenoids belonging to the guaiane, 4α,9α,10α-trihydroxyguaia-11(13)en-12,6α-olide (1), and germacrane, 9ß-hydroxyparthenolide-9-O-ß-D-glucopyranoside (2), classes have been isolated from the leaves of the Saudi medicinal plant Anvillea garcinii along with seven known compounds (3-9). The structures of the new metabolites were elucidated by spectroscopic analysis, including one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). The antimicrobial properties of 1-9 were screened against seven different pathogenic microbes, and compounds 1-3 showed a potent antifungal activity.

Effect of olive leaves extract on the antidiabetic effect of glyburide for possible herb-drug interaction.

The concomitant use of olive leaves (OL) and glyburide (GLB) is a possible therapy for diabetic patients. However, there is no report about the effect of OL on the antidiabetic effect of GLB till now. In the current study, the possible interaction of olive leaves extract (OLE) with GLB was assessed to determine if there was any pharmacological benefit over GLB alone. Seven groups of male Sprague Dawley rats were used. Normal rats of the 1st group treated with 2 mL/kg of 3% Tween 80 (vehicle). The 2nd-5th groups were diabetic rats received vehicle, GLB (5 mg/kg), OLE low dose and OLE high dose respectively, while the 6th-7th groups administered combinations of GLB plus OLE low dose and GLB plus OLE high dose, respectively. All treatments were administered orally once daily for 8 weeks. The use of GLB+OLE-500 obviously improved fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c) in diabetic rats (95.5 ±â€¯5.55 mg/dL, 6.8 ±â€¯0.16 mg/dL and 6.1 ±â€¯0.29%, respectively) compared to those treated with GLB monotherapy (140.0 ±â€¯6.36 mg/dL, 5.4 ±â€¯0.19 mg/dL and 7.0 ±â€¯0.20%, respectively). The lipid profile [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] was significantly improved in diabetic rats exposed to GLB+OLE-500 (35.6 ±â€¯1.51 mg/dL, 48.5 ±â€¯2.74 mg/dL, 25.1 ±â€¯1.21 mg/dL and 17.0 ±â€¯0.82 mg/dL, respectively) in comparison with diabetic group exposed to GLB alone (43.2 ±â€¯2.15 mg/dL, 56.8 ±â€¯2.14 mg/dL, 18.6 ±â€¯0.96 mg/dL, 23.0 ±â€¯1.26 mg/dL, respectively). Additionally, the benefit impacts of GLB+OLE-500GLB+OLE-500 therapy on the antioxidant and lipid peroxidation parameters in the pancreatic tissues of diabetic rats were higher than those of GLB monotherapy. Moreover, GLB plus OLE-500 combination had the greatest effect on restoration of the insulin content of Beta (ß) cells and reduction of the glucagon and somatostatin of Alpha (α) and Delta (δ) endocrine cells in the pancreatic islets among the different treatment. The current study suggests that OL and GLB combination could cause herb-drug interactions through modulation of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes expression in the liver of diabetic rats.

Molecular and biochemical monitoring of the possible herb-drug interaction between Momordica charantia extract and glibenclamide in diabetic rats.

Momordica charantia is used in folk medicine to manage diabetes mellitus. In this study, we investigated the possible herb-drug interaction between M. charantia fruit extract (MCFE) and glibenclamide (GLB) in streptozotocin-diabetic rats. Rats were divided into 7 groups. The 1st group received 3% Tween 80. The 2nd-5th groups were diabetic rats received vehicle, GLB (5 mg/kg), MCFE (250 and 500 mg/kg), respectively. The 6th-7th groups administered GLB plus MCFE (250 and 500 mg/kg), respectively. After 8 weeks, fasting blood glucose (FBG), insulin and glycosylated hemoglobin (HbA1c) levels were assessed. Histopathological and immunohistochemical examinations of the pancreases were done. Quantitative RT-PCR was used to analyze hepatic mRNA expression of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes. All medicaments greatly reduced FBG in diabetic rats when compared with diabetic control group. GLB plus MCFE combination was better than GLB alone in improving levels of insulin and HbA1c. All medicaments restored insulin content of pancreatic ß-cells and reduced glucagon and somatostatin of alpha and delta endocrine cells. Moreover, GLB plus MCFE-500 was the most efficient in restoring INR, Slc2a2 and PPAR-α mRNA expression to their normal levels. In conclusion, MCFE in combination with GLB gives greater glycemic improvement than GLB monotherapy.

Proanthocyanidins from the stem bark of Rhus tripartita ameliorate methylgloxal-induced endothelial cell apoptosis.

In traditional Arabian medicine, the Rhus tripartita plant (family Anacardiaceae) has been used to treat inflammatory conditions. Although Rhus extracts have been reported for their cardioprotective effects, information regarding their active principle compounds remains insufficient. The present investigation was aimed at determining the antioxidant chemical constituents of the methanolic extract of R. tripartita stem bark and evaluating their ability to ameliorate methylglyoxal-induced endothelial cell apoptosis. Ten flavonoid compounds (1-10) were isolated and identified using DPPH radical scavenging bioassay-guided chromatographic separation. A new proanthocyanidin (rhuspartin) (1) was isolated and identified as 3,5,13,14-flavantetrol-(4ß→8)-catechin, using extensive spectroscopic data and high resolution-mass spectrometry. Among the compounds (1, 5, 7-10) tested for toxicity toward cultured endothelial cells (HUVECs), the non-cytotoxic compounds 1 and 7 evinced cytoprotective potential that reversed the methylglyoxal-induced apoptosis (by 62% and 64%, respectively) through downregulation of caspase 3/7.

Molluscicidal activity of cardiac glycosides isolated from Adenium obesum.

BACKGROUND: Terrestrial mollusks are one of most important agricultural pests worldwide. Natural phytochemicals have an extended history as a source of pesticides. This study was planned to isolate molluscicidal active compounds from the stems of Adenium obesum. RESULTS: The benzene-soluble fraction of the hydroethanolic extract displayed the most potent molluscicidal activity against Monacha obstructa among different solvent fractions with a median lethal dose (LD50 ) of 4.91 µg g-1 body weight (bw). The bioactivity-guided chemical exploration of the benzene-soluble fraction led to the isolation of two known cardiac glycosides, cerberin and neriifolin which showed significant molluscicidal activity with LD50 values of 5.39 and 4.3 µg g-1 bw, respectively. CONCLUSION: Isolation of the cardiac glycoside neriifolin from A. obesum and the molluscicidal activity of cerberin and neriifolin against terrestrial snails are reported for the first time. © 2019 Society of Chemical Industry.