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

Acharya Balkrishna; Siva Kumar Solleti; Hoshiyar Singh; Niti Sharma; Anurag Varshney

doi:10.1055/a-1438-2816

Planta Medica, Table of Contents

Planta Med 2022; 88(06): 466-478
DOI: 10.1055/a-1438-2816

Natural Product Chemistry and Analytical Studies

Original Papers

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

Acharya Balkrishna

¹Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India

²Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Haridwar, Uttarakhand, India

³Patanjali UK Trust, Glasgow, Scotland, United Kingdom

,

Siva Kumar Solleti‡

¹Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India

,

Hoshiyar Singh‡

¹Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India

,

Niti Sharma

¹Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India

,

Anurag Varshney

¹Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand, India

²Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Haridwar, Uttarakhand, India

› Author Affiliations

Abstract

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-1β, TNF-α, and interleukin-6 cytokines into the peritoneal cavity as identified by ELISA. Liver (glutathione peroxidase, glutathione, glutathione disulfide, superoxide dismutase, malondialdehyde, 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-κB/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-κB/activator protein 1 pathway.

Key words

peritonitis - cytokines - oxidative stress - Ashwagandha - anti-inflammatory - antioxidant - Withania somnifera - Solanaceae

Full Text

References

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