Grosvenorine (Monk Fruit flavonoid) Attenuates Indomethacin-mediated Gastropathy in Vivo: Role of P53/Bcl-2, Antioxidant, and Inflammatory Mediators

Abstract

Natural products have gained renewed interest as therapeutic agents due to their safer effects compared to medicinal therapeutics. As a major flavonoid of Siraitia grosvenorii, Grosvenorine (GVN) has been used for many health purposes. The present study was geared to unveil the marginal safety dosage and gastroprotective potential of GVN in indomethacin-provoked gastropathy in rats. Thirty Sprague-Dawley rats were arbitrarily grouped and pre-treated with either normal saline (groups A and B), 20 mg/kg omeprazole (C), 30 mg/kg GVN (D), or 60 mg/kg GVN (E). Rats in groups B-E received indomethacin (30 mg/kg) and were euthanized for the histopathological and biochemical investigations. Oral delivery of GVN (250 and 500 mg/kg) did not cause any noticeable toxic signs even after a two-week trial. Pretreatment with GVN (30 and 60 mg/kg) significantly inhibited indomethacin-mediated gastric lesion incidence by 69.03% and 74.89%, respectively. The GVN attenuated gastric histological changes (lowered hemorrhagic/lesion areas and gastric tissue disruptions) and strengthened gastric defensive components (mucin/glycoprotein secretion and gastric pH). GVN pretreatment down-regulated apoptotic rates (increased Bcl-2 and lowered P53 proteins) and significantly heightened antioxidant markers (increased glutathione peroxidase, catalase, and superoxide dismutase contents) in gastric tissues exposed to indomethacin-ulceration. The indomethacin-induced lipid peroxidation (MDA) and inflammatory mediators (TNF-α, interleukin-6) were significantly lower in GVN-treated rats, denoting a preserved gastric homeostatic environment. These outcomes demonstrate that GVN exhibits increased gastroprotective potentials via modulation of apoptosis, antioxidant, and inflammatory mediators, making it a viable source for biopharmaceutical/nutraceutical production.

Keywords Antioxidant, Gastric ulcer, Grosvenorine, Immunohistochemistry, Inflammation