Insulin resistance contributes to several disorders including type 2 diabetes and cardiovascular diseases. Carpachromene is a natural active compound that inhibits α-glucosidase enzyme. The aim of the present study is to investigate the potential activity of carpachromene on glucose consumption, metabolism and insulin signalling in a HepG2 cells insulin resistant model. A HepG2 insulin resistant cell model (HepG2/IRM) was established. Cell viability assay of HepG2/IRM cells was performed after carpachromene/metformin treatment. Glucose concentration and glycogen content were determined. Western blot analysis of insulin receptor, IRS1, IRS2, PI3k, Akt, GSK3, FoxO1 proteins after carpachromene treatment was performed. Phosphoenolpyruvate carboxykinase (PEPCK) and hexokinase (HK) enzymes activity was also estimated. Viability of HepG2/IRM cells was over 90% after carpachromene treatment at concentrations 6.3, 10, and 20 µg/mL. Treatment of HepG2/IRM cells with carpachromene decreased glucose concentration in a concentration- and time-dependant manner. In addition, carpachromene increased glycogen content of HepG2/IRM cells. Moreover, carpachromene treatment of HepG2/IRM cells significantly increased the expression of phosphorylated/total ratios of IR, IRS1, PI3K, Akt, GSK3, and FoxO1 proteins. Furthermore, PEPCK enzyme activity was significantly decreased, and HK enzyme activity was significantly increased after carpachromene treatment. The present study examined, for the first time, the potential antidiabetic activity of carpachromene on a biochemical and molecular basis. It increased the expression ratio of insulin receptor and IRS1 which further phosphorylated/activated PI3K/Akt pathway and phosphorylated/inhibited GSK3 and FoxO1 proteins. Our findings revealed that carpachromene showed central molecular regulation of glucose metabolism and insulin signalling via IR/IRS1/ PI3K/Akt/GSK3/FoxO1 pathway.

Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. Natural products as sesame were reported to exhibit potential to protect from COVID-19 disease. In our study, the total methanolic extract of Sesamum indicum L. seeds (sesame) were led to isolation of seven known compounds, five lignan; sesamin 1, sesamolin 2, pinoresinol 3, hydroxymatairesinol 6, spicatolignan 7, together with two simple phenolic compounds; ferulic acid 4 and vanillic acid 5. All isolated compounds were evaluated in silico against three important SARS-CoV-2 protein targets; main protease (M^pro), papain-like protease (PL^pro) and RNA-dependent RNA polymerase (RdRp) which possessed crucial role in replication and proliferation of the virus inside the human cell. The results revealed that compound 6 has the high affinity against the three main proteins, specially towards the SARS-CoV-2 M^pro that exceeded the currently used SARS-CoV-2 M^pro inhibitor darunavir as well as, exhibiting a similar binding energy at SARS CoV-2 PLpro when compared with the co-crystallized ligand. This activity continued to include the RdRp as it displayed a comparable docking score with remdesivir. Inferiorly, compounds 1 and 2 showed also similar triple inhibitory effect against the three main proteins while compound 7 exhibited a dual inhibitory effect against SARS CoV-2 PL^Pro and RdRp. Further molecular dynamic simulation experiments were performed to validate these docking experiments and to calculate their binding free energies (ΔGs). Compounds 1, 2, 3, 6, and 7 showed comparable binding stability inside the active site of each enzyme with ΔG values ranged from −4.9 to −8.8 kcal mol⁻¹. All the compounds were investigated for their ADME and drug likeness properties, which showed acceptable ADME properties and obeying Lipinski's rule of five parameters. It can be concluded that the isolated compounds from sesame lignans could be an alternative source for the development of new natural leads against COVID-19.

Metabolic profiling of the crude methanolic extract of Ficus benghalensis leaves has revealed the presence of different phenolic and nitrogenous compounds including cerebrosides and tetrapyrrole pigments. A phytochemical study of the ethyl acetate fraction resulted in the identification of three known compounds, namely carpachromene (1), alpha amyrine acetate (2), and mucusoside (3) together with one new fatty acid glycoside, named 2-O-α-L-rhamnopyranosyl-hexacosanoate-β-D-glucopyranosyl ester (4). The compounds were identified using 1D, 2D NMR, and HR-ESIMS techniques as well as via comparison to other literature. Studies on the acetylcholinesterase inhibition potential and antioxidant activity were carried out on the total methanolic leaf extract, ethyl acetate fraction, and the isolated compounds. The results revealed the potent acetylcholinesterase inhibition of mucusoside alongside a new compound. Docking studies were also performed to confirm the possible interaction between the isolated compounds and acetylcholinesterase accompanying Alzheimer's disease progress.

Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic activity of the FAG on RAW 264.7 macrophages was evaluated with an MTT assay. The levels of PGE2 and NO and the activity of iNOS, COX-1, and COX-2 enzymes in LPS-stimulated RAW 264.7 cells were evaluated. The gene expression of IL-6, TNF-α, and PGE2 was investigated by qRT-PCR. The expression of epidermal growth factor receptor (EGFR), Akt, and PI3K proteins was examined using Western blotting analysis. Furthermore, molecular docking of the new FAG against EGFR was investigated. A non-cytotoxic concentration of FAG increased NO release and iNOS activity, inhibited COX-1 and COX-2 activities, and reduced PGE2 levels in LPS-stimulated RAW 264.7 cells. It diminished the expression of TNF-α, IL-6, PGE2, EGFR, Akt, and PI3K. Furthermore, the molecular docking study proposed the potential direct binding of FAG with EGFR with a high affinity. This study showed that FAG is a natural EGFR inhibitor, NO-releasing, and COX-inhibiting anti-inflammatory agent via EGFR/Akt/PI3K pathway inhibition.

In the present study, we investigated the hypoglycemic effect of different extracts (i.e.organic and aqueous) derived from the fruits ofHyphaene thebaica(doum) on male streptozotocin-induced diabetic rats.

COVID 19; an infectious disease; firstly identified in December 2019 in Wuhan, China and has since spread globally, resulting in an ongoing pandemic. Searching for protease inhibitors is a challenging task in controlling COVID 19. Genus Ficus is known to be a rich source of phenolic compounds. Metabolic profiling of leaves methanolic extract of Ficus microcarpa (Moraceae) revealed nine compounds (1–9) mainly phenolics. Docking studies concerning these compounds against SARS-CoV-2 main protease showed that quercetin 3,7-O-α-L-dirhamnoside (1) and rutin (3) possessed significant binding stability at the N3 binding site in different activity degrees, which is comparable with COVID-19 main protease inhibitor, darunavir. Our study suggests that compounds quercetin 3,7-O-α-L-dirhamnoside and rutin might be potential candidates for the development of therapies against SARS-CoV-2. Graphical Abstract