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Bioactive compound (5E,7E)-4,5,6 trihydroxy-3-(hydroxymethyl)tetrahydro-2H-pyran-2-ylheptadeca-5,7-dienoate (compound 2) was isolated from Euclea crispa (E. crispa) by the chromatographic methods. Further, the compound was confirmed by spectroscopic techniques such as ultraviolet-visible (UV/Vis) spectrometer, Fourier transform infrared (FTIR) spectrometer, and 1H and 13C nuclear magnetic resonance (NMR). Compound 2 exhibited a significant antioxidant activity with IC50 values. It restrained the auxesis of HO-8910 cells in a shot-dependent mode. CXCR4, HER2, and Akt proteins involved in cell proliferation and metastasis were found to be significantly reduced (p < 0.05). The protein that is responsible for the death of cells (Bcl-2 and Bcl-xL) was reduced (p < 0.05), while the protein expression of p53 and caspase-9 was increased (p < 0.05) in compound 2-treated HO-8910 cells. The results of molecular docking analysis showed the binding affinity with CXCR4 and HER2. Thus, compound 2 can serve as a promising chemotherapeutic agent for the intervention of ovarian cancer. The findings of this study conclude that compound 2 from E. crispa might work as a potential antioxidative and chemotherapeutic agent. The in vivo studies and attempts will pave way for this compound to be an effective drug hereafter. [ABSTRACT FROM AUTHOR]

COVID-19 is more virulent and challenging to human life. In India, the Ministry of AYUSH recommended some strategies through Siddha, homeopathy, and other methods to effectively manage COVID-19 (Guidelines for AYUSH Clinical Studies in COVID-19, 2020). Kabasura Kudineer and homeopathy medicines are in use for the prevention and treatment of COVID-19 infection; however, the mechanism of action is less explored. This study aims to understand the antagonist activity of natural compounds found in Kabasura Kudineer and homeopathy medicines against the SARS-CoV-2 using computational methods. Potential compounds were screened against NSP-12, NSP-13, NSP-14, NSP-15, main protease, and spike proteins. Structure-based virtual screening results shows that, out of 14,682 Kabasura Kudineer compounds, the 250395, 129677029, 44259583, 44259584, and 88583189 compounds and, out of 3,112 homeopathy compounds, the 3802778, 320361, 5315832, 14590080, and 74029795 compounds have good scoring function against the SARS-CoV-2 structural and nonstructural proteins. As a result of docking, homeopathy compounds have a docking score ranging from −5.636 to 13.631 kcal/mol, while Kabasura Kudineer compounds have a docking score varying from −8.290 to −13.759 kcal/mol. It has been found that the selected compounds bind well to the active site of SARS-CoV-2 proteins and form hydrogen bonds. The molecular dynamics simulation study shows that the selected compounds have maintained stable conformation in the simulation period and interact with the target. This study supports the antagonist activity of natural compounds from Kabasura Kudineer and homeopathy against SARS-CoV-2's structural and nonstructural proteins. [ABSTRACT FROM AUTHOR]

Nutritional overload in the form of high-fat and nonglycolysis sugar intake contributes towards the accelerated creation of reactive oxygen species (ROS), hyperglycemia, and dyslipidemia. Glucose absorption and its subsequent oxidation processes in fat and muscle tissues alter as a consequence of these modifications. Insulin resistance (IR) caused glucose transporter 4 (GLUT4) translocation to encounter a challenge that manifested itself as changes in glycolytic pathways and insulin signaling. We previously found that beta (β)-sitosterol reduces IR in fat tissue via IRS-1/PI3K/Akt facilitated signaling due to its hypolipidemic and hypoglycemic activity. The intention of this research was to see whether the phytosterol β-sitosterol can aid in the translocation of GLUT4 in rats fed on high-fat diet (HFD) and sucrose by promoting Rab/IRAP/Munc 18 signaling molecules. The rats were labeled into four groups, namely control rats, HFD and sucrose-induced diabetic control rats, HFD and sucrose-induced diabetic rats given oral dose of 20 mg/kg body wt./day of β-sitosterol treatment for 30 days, and HFD and sucrose-induced diabetic animals given oral administration of 50 mg/kg body wt./day metformin for 30 days. Diabetic rats administered with β-sitosterol and normalized the titers of blood glucose, serum insulin, serum testosterone, and the status of insulin tolerance and oral glucose tolerance. In comparison with the control group, β-sitosterol effectively regulated both glycolytic and gluconeogenesis enzymes. Furthermore, qRT-PCR analysis of the mRNA levels of key regulatory genes such as SNAP23, VAMP-2, syntaxin-4, IRAP, vimentin, and SPARC revealed that β-sitosterol significantly regulated the mRNA levels of the above genes in diabetic gastrocnemius muscle. Protein expression analysis of Rab10, IRAP, vimentin, and GLUT4 demonstrated that β-sitosterol had a positive effect on these proteins, resulting in effective GLUT4 translocation in skeletal muscle. According to the findings, β-sitosterol reduced HFD and sucrose-induced IR and augmented GLUT4 translocation in gastrocnemius muscle through insulin signaling modulation via Rab/IRAP/Munc 18 and glucose metabolic enzymes. The present work is the first of its kind to show that β-sitosterol facilitates GLUT4 vesicle fusion on the plasma membrane via Rab/IRAP/Munc 18 signaling molecules in gastrocnemius muscle. [ABSTRACT FROM AUTHOR]