Livogrit Prevents Methionine-Cystine Deficiency Induced Nonalcoholic Steatohepatitis by Modulation of Steatosis and Oxidative Stress in Human Hepatocyte-Derived Spheroid and in Primary Rat Hepatocytes
Authors
Acharya Balkrishna
aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
Vivek Gohel
aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
Priya Kumari
aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
Moumita Manik
aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
Kunal Bhattacharya
aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
Rishabh Dev
aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
Anurag Varshney
aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
ABSTRACT
The prevalence of nonalcoholic steatohepatitis (NASH), characterized by fatty liver, oxidative injury, and inflammation, has considerably increased in the recent years. Due to the complexity of NASH pathogenesis, compounds which can target different mechanisms and stages of NASH development are required. A robust screening model with translational capability is also required to develop therapies targeting NASH. In this study, we used HepG2 spheroids and rat primary hepatocytes to evaluate the potency of Livogrit, a tri-herbal Ayurvedic prescription medicine, as a hepatoprotective agent. NASH was developed in the cells via methionine and cystine-deficient cell culture media. Livogrit at concentration of 30 µg/mL was able to prevent NASH development by decreasing lipid accumulation, ROS production, AST release, NFκB activation and increasing lipolysis, GSH (reduced glutathione), and mitochondrial membrane potential. This study suggests that Livogrit might reduce the lipotoxicity-mediated ROS generation and subsequent production of inflammatory mediators as evident from the increased gene expression of FXR, FGF21, CHOP, CXCL5, and their normalization due to Livogrit treatment. Taken together, Livogrit showed the potential as a multimodal therapeutic formulation capable of attenuating the development of NASH. Our study highlights the potential of Livogrit as a hepatoprotective agent with translational possibilities.
KEYWORDS: NASH, ayurveda, livogrit, oxidative stress, HepG2, spheroid, steatosis
Author Biographies
Acharya Balkrishna, aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
cPatanjali Yog Peeth (UK) Trust, Glasgow, UK
Anurag Varshney, aDrug Discovery and Development Division, Patanjali Research Institute, Governed by Patanjali Research Foundation Trust, Haridwar, India
dSpecial Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, India
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