Protective and ameliorative effects of Picrorhiza kurroa rhizome extract against drug-induced liver injury in rats model
DOI:
https://doi.org/10.15584/ejcem.2025.1.6Keywords:
antioxidant activity, hepatoprotective effects, liver damage, Picrorhiza kurroaAbstract
Introduction and aim. The study evaluated the hepatoprotective and antioxidant properties of Picrorhiza kurroa rhizome ex tracts in rats, assessing their ability to scavenge free radicals and protect against liver damage.
Material and methods. Liver damage was observed in Wistar rats after seven days of oral paracetamol (PCM) and azithromycin (AZM) combination therapy, with serum biomarkers evaluated for effect.
Results. During the DPPH experiment, the antioxidant DPPH assay on rats’ livers revealed that the ethanol extract of P. kurroa demonstrated free radical scavenging activity. The crude ethanol extract of P. kurroa showed a 15.62% yield and 48.62 IC50 values in an antioxidant DPPH experiment. Long-term treatment reduces liver toxicity by balancing biochemical factors. When compared to the group that received only PCM and AZM, the rats treated with P. kurroa crude extract showed a significant decrease in alkaline phosphatase, aspartate aminotransferase, glutamate pyruvic transaminase, and bilirubin (p<0.001) while showing an increase in protein and albumin at all doses (p<0.05). In addition, it was reproved by in vivo antioxidant parameters such as superoxide dismutase, lactate dehydrogenase, catalase, and glutathione, which were also examined to verify its strong hepatoprotective effect.
Conclusion. The study found that the ethanolic extract of P. kurroa rhizome has the potential to protect against liver damage caused by PCM and AZM due to its complementary anti-oxidant properties.
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Niknahad H, Heidari R, Alzuhairi AM, Najibi A. Mitochondrial dysfunction as a mechanism for pioglitazone-induced injury toward HepG2 cell line. Pharm Sci. 2014;20(4):169-174.
Fisher K, Vuppalanchi R, Saxena R. Drug-Induced Liver Injury. Arch Pathol Lab Med. 2015;139(7):876-887. doi: 10.5858/arpa.2014-0214-RA
Arvanitakis K, Koufakis T, Kalopitas G, Papadakos SP, Kotsa K, Germanidis G. Management of type 2 diabetes in patients with compensated liver cirrhosis: Short of evidence, plenty of potential. Diabetes Metab Syndr. 2024;18(1):102935. doi: 10.1016/j.dsx.2023.102935
Chojkier M. Troglitazone and liver injury: in search of answers. Hepatology. 2005;41(2):237-246.
Segovia-Zafra A, Di Zeo-Sánchez DE, López-Gómez C, et al. Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction. Acta Pharm Sin B. 2021;11(12):3685-3726. doi: 10.1016/j.apsb.2021.11.013
Allison R, Guraka A, Shawa IT, Tripathi G, Moritz W, Kermanizadeh A. Drug induced liver injury–a 2023 update. J Toxicol Environ Health B. 2023;26(8):442-467.
Deng X, Luyendyk JP, Ganey PE, Roth RA. Inflammatory stress and idiosyncratic hepatotoxicity: hints from animal models. Pharmacol Rev. 2009;61(3):262-282. doi: 10.1124/pr.109.001727
Ilukho FA, Fasipe OJ, Aigbe FR. Evaluating the hepatoprotective, ameliorative and antioxidant potentials of the crude aqueous leafy extracts of Mangifera indica plant against acute paracetamol-induced hepatotoxicity in a mouse model. Futur Sci OA. 2022;8(6):FSO801.
Mihajlovic M, Vinken M. Mitochondria as the target of hepatotoxicity and drug-induced liver injury: molecular mechanisms and detection methods. J Mol Sci. 2022;23(6):3315. doi: 10.3390/ijms23063315
Szabo C, Ransy C, Módis K, et al. Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part I. Biochemical and physiological mechanisms. Br J Pharmacol. 2014;171(8):2099-2122. doi: 10.1111/bph.12369
Kalas MA, Chavez L, Leon M, Taweesedt PT, Surani S. Abnormal liver enzymes: A review for clinicians. World J Hepatol. 2021;13(11):1688-1698. doi: 10.4254/wjh.v13.i11.1688
Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172(3):367-379. doi: 10.1503/cmaj.1040752
Green RM, Flamm S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology. 2002;123(4):1367-1384. doi: 10.1053/gast.2002.36061
Chadha MS, Walimbe AM, Chobe LP, Arankalle VA. Comparison of etiology of sporadic acute and fulminant viral hepatitis in hospitalized patients in Pune, India during 1978-81 and 1994-97. Indian J Gastroenterol. 2003;22:11-15.
Narjes H, Nehmiz G. Effect of hospitalisation on liver enzymes in healthy subjects. Eur J Clin Pharmacol. 2000;56:329-333. doi: 10.1007/s002280000142
Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology. 2003;37(6):1475-1492. doi: 10.1053/jhep.2003.50252
Contreras-Zentella ML, Hernández-Muñoz R. Is liver enzyme release really associated with cell necrosis induced by oxidant stress?. Oxid Med Cell Longev. 2016;(1):3529149. doi: 10.1155/2016/3529149
David S, Hamilton JP. Drug-induced liver injury. US Gastroenterol Hepatol Rev. 2010;6:73.
Lala V, Zubair M, Minter D. Liver function tests. StatPearls. 2023.
Iluz-Freundlich D, Zhang M, Uhanova J, Minuk GY. The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease. Ann Hepatol. 2020;19(2):204-208. doi: 10.1016/j.aohep.2019.08.004
Gupta M, Choudhury PS, Singh S, Hazarika D. Liver functional volumetry by Tc-99m mebrofenin hepatobiliary scintigraphy before major liver resection: a game changer. Indian J Nucl Med. 2018;33(4):277-283. doi: 10.4103/ijnm.IJNM_72_18
Pandey B, Baral R, Kaundinnyayana A, Panta S. Promising hepatoprotective agents from the natural sources: a study of scientific evidence. Egyp Liver J. 2023;13(1):14. doi: 10.1016/j.jep.2021.114588
Al-Snai A, Mousa H, Majid WJ. Medicinal plants possessed hepatoprotective activity. IOSR J Pharm. 2019;9(8):26-56.
Prasathkumar M, Anisha S, Dhrisya C, Becky R, Sadhasivam S. Therapeutic and pharmacological efficacy of selective Indian medicinal plants–a review. Phytomed Plus. 2021;1(2):100029.
Singh B, Saxena AK, Chandan BK, Agarwal SG, Bhatia MS, Anand KK. Hepatoprotective effect of ethanolic extract of Eclipta alba on experimental liver damage in rats and mice. Phytother Res. 1993;7(2):154-158.
Syed SN, Rizvi W, Kumar A, Khan AA, Moin S, Ahsan A. Antioxidant and hepatoprotective activity of ethanol extract of Valeriana wallichii in CCL4 treated rats. BJPR. 2014;4(8):1004-1013.
Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. “Silymarin”, a promising pharmacological agent for treatment of diseases. Ir J Basic Med Sci. 201;14(4):308.
Kshirsagar A, Ingawale D, Ashok P, Vyawahare N. Silymarin: A comprehensive review. Pharmacogn Rev. 2009; 3(5):126.
Kumar P, Shukla SK. Hepatoprotective efficacy of Picrorhiza kurroa in experimentally induced hepatotoxicity in cockerels. Int J Curr Microbiol Appl Sci. 2017;6(4).
Vaidya AB, Sirsat SM, Doshi JC, Antarkar DS. Selected medicinal plants and formulations as hepato-biliary drugs: An Over-view. Indian J Clin Pharmacol Ther. 1996;17:7.
Chander R, Kapoor NK, Dhawan BN. Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of superoxide anions. Biochem Pharmacol. 1992;44(1):180-183.
Masood M, Arshad M, Qureshi R, et al. Picrorhiza kurroa: An ethnopharmacologically important plant species of Himalayan region. PAB. 2015;4(3):407.
Kapoor LD. CRC handbook of Ayurvedic medicinal plants. CRC press; 2018.
Council of Scientific & Industrial Research (India). The Wealth of India: a dictionary of Indian raw materials and industrial products. CSIR. 1972;9.
Gupta BM, Kumar S, Khanna HK. Science in India: Performance of Council of Scientific and Industrial Research laboratories based on the productivity profile of scientists. Res Eval. 1999;8(3):177-187.
Ahmad B, Akhtar J. Unani system of medicine. Pharmacogn Rev. 2007;1(2):210.
Kinghorn AD. Pharmacognosy in the 21st century. J Pharm Pharmacol. 2001;53(2):135-148.
Braca A, De Tommasi N, Di Bari L, Pizza C, Politi M, Morelli I. Antioxidant principles from bauhinia t arapotensis. J Nat Prod. 2001;64(7):892-895. doi: 10.1021/np0100845
Baliyan S, Mukherjee R, Priyadarshini A, et al. Determination of antioxidants by DPPH radical scavenging activity and quantitative phytochemical analysis of Ficus religiosa. Molecules. 2022;27(4):1326. doi: 10.3390/molecules27041326
Bhaskar A, Nithya V. Evaluation of the wound-healing activity of Hibiscus rosa sinensis L (Malvaceae) in Wistar albino rats. Indian J Pharmacol. 2012;44(6):694-698. doi: 10.4103/0253-7613.103252.
Zarei MH, Lorigooini Z, Khoei HA, Bijad E. Acute oral toxicity assessment of galbanic acid in albino rat according to OECD 425 TG. Toxicol. Rep. 2023;11:111-115. doi: 10.1016/j.toxrep.2023.07.001
Singh H, Prakash A, Kalia AN, Majeed AB. Synergistic hepatoprotective potential of ethanolic extract of Solanum xanthocarpum and Juniperus communis against paracetamol and azithromycin induced liver injury in rats. J Tradit Complement Med. 2016;6(4):370-376. doi: 10.1016/j.jtcme.2015.07.005
Zakaria ZA, Kamisan FH, Kek TL, Salleh MZ. Hepatoprotective and antioxidant activities of Dicranopteris linearis leaf extract against paracetamol-induced liver intoxication in rats. Pharm Biol. 2020;58(1):478-489. doi: 10.1080/13880209.2020.1764058
Manokaran S, Jaswanth A, Sengottuvelu S, et al. Hepatoprotective activity of Aerva lanata Linn. against paracetamol induced hepatotoxicity in rats. Res J Pharm. Technol. 2008;1(4):398-400.
Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47(3):469-474.
Aebi H. Catalase in vitro. Methods in enzymology 1984;105: 121-126.
Rosati G, Gherardi G, Grigoletto D, et al. Lactate Dehydrogenase and Glutamate Pyruvate Transaminase biosensing strategies for lactate detection on screen-printed sensors. Catalysis efficiency and interference analysis in complex matrices: from cell cultures to sport medicine. Sens Bio-Sens Res. 2018;21:54-64.
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70-77.
Radwan DA, Hussin MA, Mahmoud A. Antioxidant Approach of Nigella Sativa, Vit C and Silymarin for amelioration of Azithromycin induced Hepatotoxicity: Histological, Immunohistochemical and Biochemical study. Egypt Soc Clin. 2021;9(2):29-45.
Aghemo A, Alekseeva OP, Angelico F, et al. Role of silymarin as antioxidant in clinical management of chronic liver diseases: A narrative review. Ann Med. 2022;54(1):1548-1560. doi: 10.1080/07853890.2022.2069854
Trivedi SP, Kumar V, Singh S, Trivedi A, Kumar M. Ethanolic root extract of Rauwolfia serpentina alleviates copper induced genotoxicity and hepatic impairments in spotted snakehead fish, Channa punctatus (Bloch, 1793). J Environ Biol. 2021;42(6):1433-1441.
Meng X, Tang GY, Liu PH, Zhao CJ, Liu Q, Li HB. Antioxidant activity and hepatoprotective effect of 10 medicinal herbs on CCl4-induced liver injury in mice. World J Gastroenterol. 2020;26(37):5629-5645. doi: 10.3748/wjg.v26.i37.5629
Thilagavathi R, Begum SS, Varatharaj SD, Balasubramaniam AK, George JS, Selvam C. Recent insights into the hepatoprotective potential of medicinal plants and plantderived compounds. Phytother. Res. 2023;37(5):2102-2118. doi: 10.1002/ptr.7821
Martinez EC, Herrera D, Mogan S, et al. Impact of silymarin supplements on liver enzyme levels: a systematic review. Cureus. 2023;15(10). doi: 10.7759/cureus.47608
Lee YY, Tee V. Hepatoprotective effects of silymarin in management of liver injury caused by tuberculosis treatment. Drugs in Context. 2023;12:2-11. doi: 10.7573/dic.2023-2-11
Hassan F, Khan AU, Zaidi SZ, Niazi MK, Ismail MA. In Vitro Antioxidant and Inhibitory Study of Picrorhiza kurroa (Kutki), Syzygium aromaticum (Loung), Lawsonia inermis (Henna), Rheum emodi (Revand Chini), Curcuma longa (Haldi) Against Lipid Per-Oxidation in Mice Brain and Liver. Dose-Resp. 2023;21(4):15593258231210431.
Gök E, Deveci E. Histopathological, immunohistochemical and biochemical alterations in liver tissue after fungicide-mancozeb exposures in Wistar albino rats. ACB. 2022;37(4):e370404. doi: 10.1590/acb370404
Vargas-Mendoza N, Angeles-Valencia M, Morales-González Á, et al. Effect of silymarin supplementation in lung and liver histological modifications during exercise training in a rodent model. J Funct Morphol. 2021;6(3):72. doi: 10.3390/jfmk6030072
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