Journal of Ethnopharmacology and Toxicology | Volume 4 Issue 1 | Pages: 19-40 | Doi : 10.37446/jet/rsa/4.1.2026.19-40

Research Article

OPEN ACCESS | Published on : 18-Mar-2026

Traditional indigenous polyherbal preparation Liv52 protects against acetaminophen-induced hepatotoxicity in mice by suppressing MAPK and caspases while augmenting Nrf2-mediated responses

Mylanayakanahosahalli Chandrashekar Indumathi
• Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore 570006, Karnataka, India.

Kamatam Swetha
• Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore 570006, Karnataka, India.

Bhadravathi Kenchappa Chandrasekhar Sagar
• Department of Neuropathology, National Institute of Mental Health and Neurosciences (Institute of National Importance), Bangalore 560029, Karnataka, India.

Santhosh‑Kumar Rashmi
• Department of Neuropathology, National Institute of Mental Health and Neurosciences (Institute of National Importance), Bangalore 560029, Karnataka, India.

K. Sandeep Prabhu
• Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology and Carcinogenesis and Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, 115 Henning Building, Pennsylvania State University, University Park, Pennsylvania 16802, USA.

Lakshminarayana Shenoy
• State Ayurveda Research Centre, Government Ayurvedic Medical College, Brindavan Extension, Tilak Nagar, Mysuru 570015, Karnataka, India.

Chu-Huang Chen
• Vascular and Medicinal Research, The Texas Heart Institute, 6770 Bertner Avenue, Houston, Texas 77030, USA.


• Gopal Kedihithlu Marathe
• Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore 570006, Karnataka, India.; Department of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore 570006, Karnataka, India.

Abstract

Acetaminophen (paracetamol/APAP) overdose is a major cause of drug-induced liver damage, linked to mitochondrial dysfunction, hepatocyte apoptosis, and oxidative stress. Liv52, an indigenous herbal formulation comprising components from 18 plants, has been suggested to offer liver protection, although its protective mechanisms are unclear. This study demonstrates Liv52's efficacy in reducing APAP-induced hepatotoxicity and oxidative stress in Wistar albino mice. Mice pre-treated with Liv52 exhibited significant decreased mortality, reduced liver injury and oxidative stress markers, as well as less adverse alterations in both their histological and ultra-structural characteristics after being exposed to APAP. Immunohistochemistry and western blot analyses indicated that Liv52 mediates protection against APAP hepatotoxicity through mechanisms involving MAPK, Nrf2/Keap-1, and caspases, thereby mitigating oxidative stress, hepatocyte apoptosis, and mitochondrial dysfunction. These findings elucidate the mechanisms by which Liv52 combats APAP-induced liver damage.

Keywords

acetaminophen, Liv52, hepatotoxicity, oxidative stress, hepatocyte apoptosis, mitochondrial dysfunction

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