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

Autor:	Balkrishna A; Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India.; Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Haridwar, Uttarakhand, India.; Patanjali UK Trust, Glasgow, Scotland, United Kingdom., Solleti SK; Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India., Singh H; Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India., Sharma N; Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India., Varshney A; Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India.; Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Haridwar, Uttarakhand, India.
Jazyk:	angličtina
Zdroj:	Planta medica [Planta Med] 2022 May; Vol. 88 (6), pp. 466-478. Date of Electronic Publication: 2021 Apr 16.
DOI:	10.1055/a-1438-2816
Abstrakt:	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 Withania somnifera (L.) Dunal using in vivo and in vitro models of endotoxin-induced inflammation and oxidative stress. The pharmacological effects of W. somnifera root extracts were evaluated using a mouse model of endotoxin (lipopolysaccharide)-induced peritonitis and various relevant human cell lines. HPLC analysis of the W. somnifera root extracts identified the presence of various bioactive withanolides. In vivo 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 W. somnifera inhibited the migration of neutrophils, lymphocytes, and monocytes and decreased the release of interleukin-1 β , TNF- α , and interleukin-6 cytokines into the peritoneal cavity as identified by ELISA. Liver (glutathione peroxidase, glutathione, glutathione disulfide, superoxide dismutase , m alondialdehyde , myeloperoxidase) and peritoneal fluid (nitrite) biochemical analysis revealed the antioxidant profile of W. somnifera . Similarly, in human HepG2 cells, W. somnifera significantly modulated the antioxidant levels. In THP-1 cells, W. somnifera decreased the secretion of interleukin-6 and TNF- α . In HEK-Blue reporter cells, W. somnifera inhibited TNF- α -induced nuclear factor- κ B/activator protein 1 transcriptional activity. Our findings suggest the pharmacological effects of root extracts of W. somnifera rich in withanolides inhibit neutrophil infiltration, oxidative hepatic damage, and cytokine secretion via modulating the nuclear factor- κ B/activator protein 1 pathway. Competing Interests: The authors declare that they have no conflict of interest. (Thieme. All rights reserved.)
Databáze:	MEDLINE
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