Withanolides from Withania somnifera Ameliorate Neutrophil Infiltration in Endotoxin-Induced Peritonitis by Regulating Oxidative Stress and Inflammatory Cytokines.

Identification of novel anti-inflammatory strategies are needed to avoid the side effects associated with the currently available therapies. Use of anti-inflammatory herbal remedies is gaining attention. The purpose of the present investigation was to evaluate the pharmacological potential of the withanolide-rich root extracts of the medical plant (L.) Dunal using and models of endotoxin-induced inflammation and oxidative stress. The pharmacological effects of root extracts were evaluated using a mouse model of endotoxin (lipopolysaccharide)-induced peritonitis and various relevant human cell lines. HPLC analysis of the root extracts identified the presence of various bioactive withanolides. challenge of mice with endotoxin resulted in the infiltration of various leukocytes, specifically neutrophils, along with monocytes and lymphocytes into the peritoneal cavity. Importantly, prophylactic treatment with inhibited the migration of neutrophils, lymphocytes, and monocytes and decreased the release of interleukin-1, TNF-, and interleukin-6 cytokines into the peritoneal cavity as identified by ELISA. Liver (glutathione peroxidase, glutathione, glutathione disulfide, , m, myeloperoxidase) and peritoneal fluid (nitrite) biochemical analysis revealed the antioxidant profile of . Similarly, in human HepG2 cells, significantly modulated the antioxidant levels. In THP-1 cells, decreased the secretion of interleukin-6 and TNF-. In HEK-Blue reporter cells, inhibited TNF--induced nuclear factor-B/activator protein 1 transcriptional activity. Our findings suggest the pharmacological effects of root extracts of rich in withanolides inhibit neutrophil infiltration, oxidative hepatic damage, and cytokine secretion via modulating the nuclear factor-B/activator protein 1 pathway.