Piperine modulates IR/Akt/GLUT4 pathways to mitigate insulin resistance: Evidence from animal and computational studies.

The global prevalence of diabetes mellitus is rising, especially in India. Medicinal herbs, whether used alone or in combination with conventional medicines, have shown promise in managing diabetes and improving overall well-being. Piperine (PIP), a major bioactive compound found in pepper, is gaining attention for its beneficial properties. This study aimed to assess whether PIP could alleviate diabetes by targeting insulin pathway-related molecules in the adipose tissue of rats on a high-fat diet (HFD). After 60 days on the HFD, rats received PIP at a dose of 40 mg/kg body weight for one month. The results showed that PIP significantly improved metabolic indicators, antioxidant enzymes, and carbohydrate metabolic enzymes. It also regulated the mRNA and protein expression of insulin signaling, which had been disrupted by the diet and sucrose intake. Molecular docking analysis also revealed strong binding of PIP to key diabetes-related regulatory proteins, including Akt (-6.2 kcal/mol), IR (-7.02 kcal/mol), IRS-1 (-6.86 kcal/mol), GLUT4 (-6.24 kcal/mol), AS160 (-6.28 kcal/mol), and ß-arrestin (-6.01 kcal/mol). Hence, PIP may influence the regulation of glucose metabolism through effective interactions with these proteins, thereby controlling blood sugar levels due to its potent antilipidemic and antioxidant properties. In conclusion, our study provides in vivo experimental evidence against the HFD-induced T2DM model for the first time, making PIP a potential natural remedy to enhance the quality of life for diabetic patients and aid in their management.

Nigella sativa L. seed extracts promote wound healing progress by activating VEGF and PDGF signaling pathways: An in vitro and in silico study.

Background: A significant area of clinical research is the development of natural wound healing products and the management of chronic wounds. Healing wounds with medicinal plants has been a practice of ancient civilizations for centuries. Nigella sativa L ( N. sativa) is a medicinal plant that has several pharmacological properties. Methods: The present study evaluated the wound healing properties of Nigella sativa L. ( N. sativa) seed extracts using normal cell lines such as normal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). The expression levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were analyzed through western blot analysis. Furthermore, computational analyses were carried out to screen the potential bioactive compounds for wound healing applications. Results: The results of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay revealed that, all the tested solvent extracts of N. sativa seeds (including ethanol, ethyl acetate, chloroform, and petroleum ether) did not exert any cytotoxic effects at the tested concentrations. Furthermore, the western blot analysis showed elevated levels of VEGF and PDGF upon treatment with N. sativa seed extracts. Gas chromatography-mass spectrometry (GC-MS) analysis of N. sativa extracts identified 268 phytocompounds. Molecular docking studies revealed that three phytocompounds of N. sativa extracts, including tricyclo[20.8.0.0(7,16)]triacontane, 1(22),7(16)-diepoxy-, adaphostin and obeticholic acid had strong binding affinity with wound healing-related target proteins, showing docking scores ranging from -5.5 to -10.9 Kcal/mol. These compounds had acceptable Absorption, Distribution, Metabolism, and Excretion (ADME) properties. Conclusions: Based on these results, N. sativa seed extracts might possess potential wound healing properties owing to the presence of a wide range of bioactive components.

Molecular docking analysis of bioactive compounds from Plectranthus amboinicus with glucokinase.

Natural remedies from medicinal plants are known to be effective and reliable appropriate medicine for illnesses. The current research examined Plectranthus amboinicus' anti diabetic property by docking the bioactive compounds of certain target proteins. We document the molecular docking analysis of bioactive compounds from Plectranthus amboinicus with protein Glucokinase. Molecular docking experiments were carried out in PyRx software. Results of these docking experiments showed that most of the compounds showed very strong interaction with the target protein Glucokinase. Based on the scoring parameters we have selected best four compounds (Rutin, Salvianolic acid, Luteolin and Salvigenin) which showed very good docking score and hydrogen bond interaction for diabetics.

Computational Study on the Inhibitory Effect of Natural Compounds against the SARS-CoV-2 Proteins.

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.

Anti-ovarian cancer potential of phytocompound and extract from South African medicinal plants and their role in the development of chemotherapeutic agents.

Ovarian cancer (OC) accounts for the highest tumor-related mortality among the gynecologic malignancies. Most of the OC patients diagnosed with advanced-stage (III and IV) this situation creates panic and provokes an emergency to discover a new therapeutic strategy. Plants that possess medicinal properties are gaining attention as they are enriched with various chemical compounds that are potential to treat various diseases. It is a prolonged process to provide innovative and significant leads against a range of pharmacological targets for a human disease management system. Though challenges and difficulties are faced in the development of a new drug, the emergence of combinatorial chemistry is providing a new ray of hope and also, the executed effort in discovering the drug, and a chemical compound has been remarkably successful. This review discussed the role of medicinal plants that are native of South Africa in treating the Ovarian Cancer and in drug discovery.

Screening of Potential Phytocompounds From Euclea crispa (Thunb.) Leaves Targeting Human Epidermal Growth Factor Receptor 2 (HER2) Signaling Pathway.

BACKGROUND: Overexpression of human epidermal growth factor receptor 2 (HER2) plays an important role in the development and progression in a variety of cancers and it is a novel therapeutic target for breast cancer and ovarian cancer. Euclea crispa (E. crispa) is a South African medicinal plant in the family Ebenaceae used in the management of different human diseases and disorders. AIMS: The aim of this study was to evaluate the potential inhibitors against HER2 from hexane extract of E. crispa leaves. MATERIALS AND METHODS: Chemical fingerprinting method was used to identify the presence of natural compounds from the extract whereas their inhibitory activities were analyzed by molecular docking analysis against HER2. Absorption, distribution, metabolism, and excretion (ADME) properties also predicted to establish the pharmacokinetics and pharmacodynamics profiles of the selected compounds. RESULTS: The molecular docking analysis expressed that phenyl glucuronide, hydrocortisone acetate, and 6-(4,6-dioxo-1,4,5,6-tetrahydropyrimidin-2-yl-amino)hexanoic acid trifluoroacetate possess good inhibitory activities with good glide score of -6.63, -5.41, and -5.40 and glide energy of -35.03, -42.51, and -31.38 kcal/mol, respectively when compared with standard Food and Drug Administration-approved drug and other compounds. All the screened compounds were within the acceptable and permissible limits of ADME properties. CONCLUSION: Thus, from this study it can be concluded that, these screened natural compounds from E. crispa leaves may serve as potential inhibitors for HER2 and they might lead to development of new therapeutic agents against cancer and its associated complications.