80 INDIAN DRUGS 60 (07) JULY 2023 BIOASSAY GUIDED HEPATOPROTECTIVE ACTIVITY OF POLYGONATUM CIRRHIFOLIUM AGAINST ISONIAZID AND RIFAMPICIN INDUCED HEPATOTOXICITY IN RATS Roma Ghai a , K. Nagarajan b , Parul Grover b *, Vinay Kumar a , Richa Goel c , Charanpreet Kaur a and Reenu Chauhan a (Received 20 June 2022) (Accepted 11 April 2023) ABSTRACT The present investigation was performed to examine the hepatoprotective effect of the aqueous ethanolic extract of Polygonatum cirrhifolium in antitubercular drug-induced liver damage. P. cirrhifolium rhizomes were crushed, dissolved in various solvents (in order of polarity), and then tested for phytochemicals. Based on their findings, mass extraction utilizing the ethanol-water mixture (50: 50) was carried out using the Soxhlet method. The doses for animal research were established through acute toxicity tests. The hepatoprotective potential of aqueous ethanolic extract (50:50) of rhizomes was determined in Wistar rats at doses of 200 mg kg -1 and 400 mg kg -1 p.o. per day. Blood samples were examined for the bio- chemical markers SGOT, SGPT, ALP, total bilirubin, and albumin. Histopathology of the liver was also conducted followed by in vitro anti-oxidant studies. Simultaneously, the extract was subjected to LCMS characterization. P. cirrhifolium extract at both the doses 200 mg kg -1 and 400 mg kg -1 has shown signifi- cant hepatoprotective activity against hepatotoxicity induced by INH+ RIF in a dose-dependent manner, as depicted by the significant changes in the values of blood biomarkers and in vitro anti-oxidant studies. Histopathological studies showed that the treatment with 200 mg kg -1 and 400 mg kg -1 of P. cirrhifolium exhibited regeneration of liver architecture and portal system by reducing the haemorrhage and inflam- matory infiltrate. LC-MS characterization showed serpentine, 5-hydroxy methylfurfural and cephalotaxine as active constituents. It can be inferred that hydroethanolic extract of P. cirrhifolium protects the liver from anti-TB induced toxicity and this protection could be due to the active phytoconstituents. a Department of Pharmacology, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad- 201 206, Uttar Pradesh, India b Department of Pharmaceutical Chemistry, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad - 201 206, Uttar Pradesh, India c Department of Pharmacognosy, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad - 201 206, Uttar Pradesh, India *For Correspondence: E-mail: parul.grvr@gmail.com https://doi.org/10.53879/id.60.07.13557 Keywords: Polygonatum cirrhifolium, hepatoprotective, hepatotoxicity, rifampicin, isoniazid, silymarin INTRODUCTION The body’s largest gland and most crucial organ is the liver. It is involved in protein secretion and storage of fat-soluble vitamins and other useful substances. It also removes toxic substances from the body 1 . But due to oxidative stress, lipid peroxidation occurs and the condition gets aggravated as a result of infections, immune disorders and high intake of alcohol. The plants which have the ability to reduce oxidative damage are considered to be hepatoprotective 2 . Many adverse effects of anti-tubercular agents have been reported, and one of the foremost toxicities is hepatotoxicity. Anti-TB drugs like isoniazid and rifampicin are the first-line standard drugs that have been reported to cause hepatotoxicity and are known to induce considerable mortality and morbidity mediated through oxidative stress. Isoniazid and rifampicin affect hepatocytes, liver vasculature and biliary epithelial cells 3,4 . P. cirrhifolium is a member of the genus Polygonatum of about 57 species belonging to the family Liliaceae or Convallariaceae. P. cirrhifolium, also known as Mahameda, Tridanti, Vasucchidra, and Devamani, consists of roots and rhizomes. It is widely distributed in China and Japan covering East Asia, Pakistan and India 5 . The presence of steroidal saponins and polysaccharides has been discovered in phytochemical investigations on this plant. Other species of the Polygonatum predominantly