Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking, and pharmacokinetics

The study comprehensively investigated the therapeutic potential of <i>Gymnema sylvestre</i> triterpenoid saponin extract (GST), encompassing its hepatoprotective, immunomodulatory, and anticancer activities. The study employed a Prednisolone (PRD)-induced immunosuppressed rat model to assess the hepatoprotective and immunomodulatory effects of GST. Using this model, GST was found to modulate haematopoiesis, improving RBC, platelet, and WBC counts, underscoring its potential in hematopoietic homeostasis. Organ atrophy, a hallmark of immunosuppression in spleen, thymus, liver, and kidneys, was reversed with GST treatment, reinforcing its hepatotrophic and organotropic capabilities. Elevated hepatic biomarkers, including alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lipid peroxidase (LPO), indicative of hepatocellular injury and oxidative stress, were reduced with GST, underscoring its hepatoprotective and antioxidative effects. Additionally, GST restored depleted antioxidants glutathione (GSH) and superoxide dismutase (SOD), highlighting its strong antioxidative capabilities. Molecular insights revealed a downregulation of interleukin-2 (IL-2) and interleukin-4 (IL-4) mRNA in the spleen of immunosuppressed rats, while GST treatment significantly upregulated IL-2 and IL-4 mRNA expression, showcasing its immunomodulatory potential. Increased levels of tumor necrosis factor-α (TNF-α) associated with immune dysregulation were effectively decreased by GST, underscoring its role in modulating inflammatory responses and restoring immune balance. Molecular docking studies indicated strong inhibition of TNF-α by GST compounds. In terms of anticancer activity, GST demonstrated significant cytotoxicity against MCF-7, and MDA-MB-231 (breast cancer cell lines). Notably, GST demonstrated biocompatibility with normal CHO (Chinese hamster ovary cell line) and HUVEC (Human umbilical vein endothelial cells) cell lines. Molecular docking studies indicated strong inhibition of breast cancer proteins HER1 and HER2 (human epidermal growth factor receptors) by GST compounds. Additionally, pharmacokinetics, bioavailability, drug-likeness, and toxicity risk predictions suggest that GST compounds are pharmacologically favourable with no adverse effects.