Research J. Pharm. and Tech. 17(10): October 2024 1 ISSN 0974-3618 (Print) www.rjptonline.org 0974-360X (Online) RESEARCH ARTICLE Pharmacological Screening of Hepatoprotective Activity of Vanillylacetone in Paracetamol Induced Hepatotoxic Rats Poonam Sahu, Aarti Tiwari, Gulshan Athbhaiya, Somnath Mandol, Pradeep Kumar Samal* Pharmacy Department, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India. *Corresponding Author E-mail: samalpharmacology@rediffmail.com ABSTRACT: Paracetamol is often used as a pain reliever and fever reducer. However, when taken in excessive amounts or used repeatedly, it may result in adverse consequences, such as liver damage. The current study aims to assess the hepatoprotective effects of Vanillylacetone against paracetamol-induced hepatotoxicity in rats, at a dosage of 2g/kg body weight administered orally. A dose of 100 mg/kg of Silymarin was administered orally as a standard reference. On the eleventh day, animals were euthanized and blood samples were collected to assess liver function using liver profile tests including ALT, AST, bilirubin, and total protein levels. The result was also validated by the histopathological examination of liver tissue samples. The administration of 400 mg vanillylacetone per kilogram of body weight per day to group-V rats resulted in a notable reduction in the levels of AST, ALT, direct and total bilirubin, and a considerable rise in total protein levels compared to group-II rats. The hepatoprotective effects of a daily dose of 400 mg vanillylacetone per kilogram were found to be similar to those of a daily dose of 100 mg silymarin per kilogram. Administration of vanillylacetone has effectively restored the aberrant levels of biochemical markers to almost normal levels, with the degree of improvement being depending on the dosage. The current investigation demonstrates that vanillylacetone provides substantial protection against hepatocellular damage generated by paracetamol. KEYWORDS: Paracetamol, Hepatoprotective, Hepatotoxicity, Vanillylacetone, Silymarin. INTRODUCTION: Hepatic illness continues to be a significant worldwide health issue, necessitating continued efforts to discover novel pharmaceuticals. Hepatic cells engage in many metabolic processes, underscoring the need of developing liver-protective drugs 1 . Excessive use or occasionally even appropriate use of some medications might cause harm to the liver. Furthermore, the levels of many biochemical indicators such as Aspartate Serum Transferase (AST), Alanine Amino Transferase (ALT), triglycerides, cholesterol, bilirubin, and alkaline phosphatase are increased 2 . Synthetic medication, when used to treat liver problems, may sometimes result in severe adverse reactions 3 . Paracetamol is a widely used over-the-counter analgesic-antipyretic medication that serves as a replacement for aspirin. Received on 25.01.2024 Modified on 13.05.2024 Accepted on 05.07.2024 © RJPT All right reserved Research J. Pharm. and Tech 2024; 17(10):. DOI: The user's text is 4 . Long-term use of Paracetamol or consumption in high quantities is often associated with liver and kidney damage in both animals and humans. Acetaminophen undergoes metabolism in the liver via the cytochrome P450 pathway, resulting in the formation of a very poisonous metabolite called N– acetyl–p–benzoquinamine (NAPQI). Typically, NAPQI is combined with glutathione and eliminated by urine 5 . An excessive amount of acetaminophen may cause damage to the mitochondria by depleting glutathione levels, leading to the development of acute liver necrosis 6 . The use of herbal remedies to treat numerous disorders, including hepatopathy, is increasing in many nations. The discovery of most crucial medications in contemporary medicine may be attributed to the major contribution of traditional knowledge about medicinal plants. Developing nations has abundant reserves of therapeutic plants. The objective of our research was to assess the hepatoprotective properties, namely the antioxidant capacity, of vanillylacetone, a medication renowned for its therapeutic potential and diverse