GC-MS profiling and evaluation of acute oral toxicity, anti-tumour, antimicrobial and antioxidant activities of Croton socotranus Balf.f. aerial parts: in-vitro, in-vivo and in-silico studies.

Croton socotranus Balf.f. shrub is widely used traditionally in Asia as an anti-infective. The study was conducted for metabolite profiling, oral acute toxicity and antioxidant studies, antimicrobial activity and anticancer effect against human hepatoma (HepG2), breast cancer (MCF-7) and rhabdomyosarcoma (RD) cells. Gas chromatography-mass spectrometry analysis revealed the presence of 39 compounds, predominantly comprising fatty acids (57.76%), sesquiterpenes (24.56%) and triterpenes (9.54%). The n-hexane fraction exhibited promising antimicrobial activity and displayed a potent anti-tumour effect against HepG2, MCF-7 and RD cells with IC50 values of 3.4, 6.5 and 7.1 µg/mL, respectively. Histological examination revealed significant morphological changes consistent with the changes observed in the apoptotic mechanism of action. The molecular docking study provided insights into the rational binding modes of the identified compounds with phosphoinositide 3-kinase and poly(ADP-ribose)polymerase-1 enzymes. Our findings suggest the potential of C. socotranus as a valuable source of antimicrobial and anticancer agents.

Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm.f. is widely used in various traditional systems of medicine worldwide. Since over 5000 years ago, several cultures have used A. vera extract medicinally for conditions ranging from diabetes to eczema. It has been shown to reduce the symptoms of diabetes by enhancing insulin secretion and protecting pancreatic islets. AIM OF THE WORK: This research study aimed to investigate the in-vitro antioxidant effect, the acute oral toxicity, and the possible pharmacological in-vivo anti-diabetic activity with histological examination of the pancreas of the standardized deep red A. vera flowers methanolic extracts (AVFME). MATERIALS AND METHODS: The liquid-liquid extraction procedure and TLC technique were used to investigate chemical composition. Total phenolics and flavonoids in AVFME were quantified by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. The present study involved evaluating the in-vitro antioxidant effect of AVFME using ascorbic acid as the reference standard, an acute oral toxicity study by using thirty-six albino rats and different concentrations of AVFME (200 mg/kg, 2, 4, 8 and 10 g/kg b.w.). Furthermore, the in-vivo anti-diabetic study was performed on alloxan-induced diabetes in rats (120 mg/kg, I.P.) and two doses of AVFME (200 and 500 mg/kg b.w., orally) were used as compared to glibenclamide (5 mg/kg, orally) as a standard hypoglycemic sulfonylurea medication. A histological examination of the pancreas was performed. RESULTS: AVFME resulted in the highest phenolic content of 150.44 ± 4.62 mg gallic acid equivalent per gram (GAE/g) along with flavonoid content of 70.38 ± 0.97 mg of quercetin equivalent per gram (QE/g). An in-vitro study revealed that the antioxidant effect of AVFME was strong as ascorbic acid. The results of the in-vivo studies showed that the AVFME didn't cause any apparent toxicity signs or death in all groups at different doses which proves the safety of this extract with a wide therapeutic index. The antidiabetic activity of AVFME demonstrated a considerable drop in blood glucose levels as glibenclamide, without severe hypoglycemia or significant weight gain which is considered an advantage of AVFME over glibenclamide use. The histopathological study of pancreatic tissues confirmed the protective effect of AVFME on the pancreatic beta-cells. The extract is proposed to have antidiabetic activity through inhibition of α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Molecular docking studies were conducted to understand possible molecular interactions with these enzymes. CONCLUSION: AVFME represents a promising alternative source of active constituents against diabetes mellitus (DM) based on its oral safety, antioxidant, anti-hyperglycemic activities, and pancreatic protective effects. These data revealed the antihyperglycemic activity of AVFME is mediated by pancreatic protective effects while significantly enhancing insulin secretion through increasing functioning beta cells. This suggests that AVFME has the potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes (T2DM).

The Potential of Jatropha variegata Fruits as a Natural Contraceptive: Antifertility Activity and Phytochemical Analysis.

BACKGROUND: Jatropha variegata (family, Euphorbiaceae) is native to Yemen, where it is commonly known as the Ebki shrub. The fruits of the plant are traditionally ingested by local women as a natural method of contraception. This study was undertaken to investigate the phytochemical content of the methanol extract of J. variegata fruits and to evaluate its antifertility potential. METHODS: Isolation of the chemical constituents was performed by chromatographic techniques, and the chemical structures of these compounds were identified by spectroscopy. The antifertility activity of the methanol extract was assessed in two experimental rat models to explore both the anti-implantation and the estrogenic/antiestrogenic activities in females. In these models, the number of successful implants, the size of litter, and body/ovary weights were all recorded. The development of ovarian follicles was also monitored via histological staining. RESULTS: Phytochemical work on the fruit extract of J. variegata led to the isolation of two oils (JF1 and JF2) and methyl elaidate. GC-MS analysis of the JF1 oil revealed that the major chemical constituents were fatty acid esters (43.77%), hydrocarbon alkanes (20.65%), and terpenoids (4.65%), while terpenoids (28.8%), fatty acids and their esters, (29.47%), and phytosterol (10.49%) were the major components found in the JF2 oil. The methanol extract of J. variegata fruit exhibited 50% and 93% abortifacient activity at 150 and 300 mg/kg doses, respectively. The extract also showed significant estrogenic activity as evidenced by the increase in rat ovary weight at a dose of 300 mg/kg compared to the control group. Histological analyses further confirmed this estrogenic activity. CONCLUSIONS: J. variegata fruits possess an antifertility activity that appeared to result from its antiembryo implantation potential and from its estrogenic activity. The bioactive constituents involved in these activities may need to be further explored and exploited in the pursuit of newer contraceptives.

Mechanism of antidiabetic effects of Plicosepalus Acaciae flower in streptozotocin-induced type 2 diabetic rats, as complementary and alternative therapy.

BACKGROUND: Diabetes and its related complications remain to be a major clinical problem. We aim to investigate the antidiabetic mechanistic actions of Plicosepalus Acaciae (PA) flowers in streptozotocin (STZ)-induced diabetic rats. METHODS: After diabetes induction, rats were divided randomly into five groups, including: 1) normal control group, 2) diabetic control group, 3) diabetic group treated with 150 mg/kg of ethanolic extract of PA flowers, 4) diabetic group treated with 300 mg/kg of ethanolic extract of PA flowers, and 5) diabetic group treated with 150 mg/kg of metformin. After 15 days of treatment; fasting blood glucose, glycated hemoglobin (HBA1c%), insulin, C-peptide, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA), triglyceride (TGs), total cholesterol (Tc), low density lipoprotein cholesterol (LDL-c), very LDL (VLDL), high DLc (HDL-c), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were assessed. Histopathology of pancreas was also assessed. RESULTS: The results showed that PA flower ethanolic extract significantly reduced blood glucose, HBA1c%, MDA, TGs, Tc, VLDL, LDL-c, TNF-α, and IL-6 levels in a dose-dependent manner. All these parameters were already increased by diabetic induction in the untreated diabetic group. Treatment of diabetic rats with PA flower increased insulin, HDL-c, GSH, catalase, and SOD levels. Histological examination showed that the PA flower caused reconstruction, repair, and recovery of damaged pancreas when compared with the untreated group. CONCLUSIONS: PA flower has a potential role in the management of diabetes as complementary and alternative therapy, due to its antioxidant, anti-inflammatory, hypolipidemic, hypoglycemic and insulin secretagogue effects.

The Yemeni Brown Algae Dictyota dichotoma Exhibit High In Vitro Anticancer Activity Independent of Its Antioxidant Capability.

The aim of this study was to investigate the anticancer and antioxidant activities as well as the safety of the brown algae Dictyota dichotoma of the Western seacoast of Yemen. Cytotoxicity of methanol extract of D. dichotoma and several of its fractions, petroleum ether, chloroform, ethyl acetate, n-butanol, and aqueous extracts against seven different cancer cell lines was determined by crystal violet staining. The antioxidant activity was also assessed using the DPPH radical scavenging assay. Acute toxicity study was performed on rats at increasing doses of the methanol extract. Extracts of D. dichotoma exerted a significant dose-dependent cytotoxicity on the seven tumor cell lines but were generally more selective on MCF-7 and PC-3. Among all fractions, the chloroform fraction of the D. dichotoma displayed the highest cytotoxic activity and was most effective in MCF-7, PC3, and CACO cells (IC50 = 1.93 ± 0.25, 2.2 ± 0.18, and 2.71 ± 0.53 µg/mL, respectively). The petroleum ether fraction was also effective, particularly against MCF-7 and PC-3 (IC50 = 4.77 ± 0.51 and 3.93 ± 0.51 µg/mL, respectively) whereas the activity of the ethyl acetate fraction was more pronounced against HepG2 and CACO (IC50 = 5.06 ± 0.21 and 5.06 ± 0.23 µg/mL, respectively). Of all the extracts tested, the crude methanolic extract of the algae exhibited only a modest antioxidant potential (IC50 = 204.6 ± 8.3 µg/mL). Doses as high as 5000 mg/kg body weight of D. dichotoma methanolic extracts were safe and well tolerated by rats. The overall results showed that D. dichotoma exhibited a significant cytotoxic activity probably due to the occurrence of nonpolar cytotoxic compounds, which is independent of its antioxidant capability.

Prenylated flavonoids from Commiphora opobalsamum stem bark.

A phytochemical study on the stem bark of Commiphora opobalsamum looking for cytotoxic compounds afforded eleven flavonoids, including six previously undescribed prenylated congeners, comophorin A-E, and comophoroside A. The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Isolated compounds were biologically evaluated using in vitro cytotoxicity MTT-based assay against two cancer cell lines; namely human hepato-cellular carcinoma (HepG-2) and human breast adenocarcinoma (MCF-7). Comophoroside A revealed to retain the strongest cytotoxic activity against MCF-7 and HepG-2 cell lines with IC50 values of 8 and 12 µg/mL, respectively.