Evaluation of hepatoprotective activity of Murvadi Agada - A polyherbal formulation in Methotrexate induced hepatotoxicity in Wistar albino rats.
DOI:
https://doi.org/10.70066/jahm.v14i4.2659Keywords:
Gara Visha, hepatoprotective activity, hepatotoxicity, Methotrexate, Murvadi Agada.Abstract
Background– In India, drug induced liver injury constitutes most cases of acute liver failure with fatality up to 50%. Murvadi Agada is a classical ayurvedic formulation indicated for the treatment of Gara Visha (concomitant poison); however, its hepatoprotective potential has not yet been scientifically evaluated. Objective- To evaluate the hepatoprotective effect of Murvadi Agada against Methotrexate induced hepatotoxicity using Wistar albino rats. Methods- Thirty Wistar albino rats of either sex were randomly divided into five groups (n=6). Group I served as normal control. Group II received single intraperitoneal injection of Methotrexate 20mg/kg and served as toxic control. Group III and IV were administered with Murvadi Agada (1080 and 2160 mg/kg) orally, respectively, followed by single intraperitoneal injection of Methotrexate. Group V received Silymarin (100 mg/kg orally) + Methotrexate. Silymarin and Murvadi Agada were administered for 7 and 14 consecutive days respectively. On the last day, single dose of Methotrexate was given one hour after drug administration. Results- Methotrexate significantly increased serum AST, ALP, IL-1β (p < 0.01), GGT (p < 0.05) compared to normal control group. Murvadi Agada 1080 mg/kg significantly decreased serum ALT (p < 0.001), ALP (p < 0.01), AST (p < 0.05); Murvadi Agada 2160 mg/kg significantly decreased serum ALT, GLDH (p < 0.001), AST, ALP (p < 0.01), GGT, IL-1β (p < 0.05) and Silymarin significantly decreased serum IL-1β (p < 0.01), AST, GLDH (p < 0.05) compared to Methotrexate group. Single dose of Methotrexate caused areas of focal necrosis in liver sections; Murvadi Agada administration caused dose dependent reduction of inflammatory infiltrate in both groups and no histological changes were observed in Silymarin group. Conclusion– Murvadi Agada demonstrated significant hepatoprotective activity against Methotrexate induced hepatotoxicity. Both doses significantly reduced liver enzymes, with the double therapeutic equivalent dose attenuating GGT, GLDH, IL-1β and histopathology protection.
References
Pugh AJ, Barve AJ, Falkner K, Patel M, McClain CJ. Drug-induced hepatotoxicity or Drug induced liver injury. Clinics in Liver Disease. 2009 May; 13(2):277-294. Available from: https://doi.org/10.1016/j.cld.2009.02.008
Wang Y, Xie W. Drug induced liver injury: An overview and update. Gastroenterology and Endoscopy. 2023 Apr;1(2):102-109. Available from: https://doi.org/10.1016/j.gande.2022.11.005
Murthy KRS (translator). Vagbhata’s Ashtanga Hridaya, Uttarasthana, chapter 35, verse no.49. 7th edition, Varanasi; Chaukhambha Krishnadas Academy; 2010; 336
Murthy KRS (translator). Vagbhata’s Ashtanga Hridaya, Uttarasthana, chapter 35, verse no.50 -53. 7th edition, Varanasi; Chaukhambha Krishnadas Academy; 2010; 336
Murthy KRS (translator). Vagbhata’s Ashtanga Hridaya, Uttarasthana, chapter 35, verse no.57 - 58. 7th edition, Varanasi; Chaukhambha Krishnadas Academy; 2010; 337
Mehrzadi S, Fatemi I, Esmaeilizadeh M, Ghaznavi H, Kalantar H, Goudarzi M, et al. Hepatoprotective effect of berberine against methotrexate-induced liver toxicity in rats. Biomedicine and Pharmacotherapy. 2018 Jan;97:233–239. Available from: https://doi.org/10.1016/j.biopha.2017.10.113
Hiremath RR, Digra R. Murvadi Agada – QC analysis, method of preparation and its us-es in current scenario. International Research Journal of Ayurveda and Yoga. 2022 Jan; 5(2):40–48. Available from: https://doi.org/10.47223/IRJAY.2022.5206
Ghosh MN. Fundamentals of Experimental Pharmacology; 3rd edition, Scientific Book Agency; Kolkata; 2003;192–197
Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology. 1957 Jul;28(1):56–63. Available from: https://doi.org/10.1093/ajcp/28.1.56
Buch I, Buch H. An improved King and Armstrong method for the determination of phosphatase activity in blood serum. Acta Medica Scandinavica. 1939 Dec;101:211–236. Available from: https://doi.org/10.1111/j.0954-6820.1939.tb07785.x
Kricka LJ, Park JY. The natural history of an eponym: the Malloy–Evelyn method. The electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (EJIFCC). 2020 Sep;31(3):190–196
Langenfeld NJ, Payne LE, Bugbee B. Colorimetric determination of urea using diacetyl monoxime with strong acids. PLoS One. 2021 Nov; 16(11):e0259760. Available from: https://doi.org/10.1371/journal.pone.0259760
Caraway WT. Determination of uric acid in serum by a carbonate method. American Journal of Clinical Pathology. 1955 Jul;25(7):840–845. Available from: https://doi.org/10.1093/ajcp/25.7_ts.0840
Liu WS, Chung YT, Yang CY, Lin CC, Tsai KH, Yang WC, et al. Serum creatinine deter-mined by Jaffe, enzymatic method, and isotope dilution–liquid chromatography–mass spectrometry in patients under hemodialysis. Journal of Clinical Laboratory Analysis. 2012 Jan;26(3):206–214. Available from: https://doi.org/10.1002/jcla.21495
Szasz G. A kinetic photometric method for serum gamma-glutamyl transpeptidase. Clinical Chemistry. 1969 Feb;15(2):124–136. Available from: https://doi.org/10.1093/clinchem/15.2.124
Schmidt ES, Schmidt FW. Glutamate dehydrogenase: biochemical and clinical aspects of an interesting enzyme. Clinica Chimica Acta. 1988 Mar;173(1):43–55. Available from: https://doi.org/10.1016/0009-8981(88)90356-7
Wroblewski F, LaDue JS. Lactic dehydrogenase activity in blood. Proceedings of the So-ciety for Experimental Biology and Medicine. 1955 Oct;90(1):210–213. Available from: https://doi.org/10.3181/00379727-90-21985
Luedde T, Kaplowitz N, Schwabe RF. Cell death and cell death responses in liver dis-ease: mechanisms and clinical relevance. Gastroenterology. 2014 Oct;147(4):765-83. Available from: https://doi.org/10.1053/j.gastro.2014.07.018
Vroon DH, Israili Z. Alkaline phosphatase and gamma glutamyltransferase. Clinical Methods: The History, Physical, and Laboratory Examinations. In: Walker HK, Hall WD, Hurst JW, editors. Boston: Butterworths; 1990; 494
Ghadir MR, Riahin AA, Havaspour A, Nooranipour M, Habibinejad AA. The relation-ship between lipid profile and severity of liver damage in cirrhotic patients. Hepatitis Monthly. 2010 Dec;10(4):285-288
Murthy KRS (translator). Vagbhata's Ashtanga Sangraha, Sutrasthana, chapter 18, verse no.14. 7th edition, Varanasi; Chaukhambha Krishnadas Academy; 2010; 339
Church RJ, Schomaker SJ, Eaddy JS, Boucher GG, Kreeger JM, Aubrecht J, et al. Gluta-mate dehydrogenase as a biomarker for mitotoxicity; insights from furosemide hepato-toxicity in the mouse. PLoS One. 2020 Oct;15(10):e0240562. Available from: https://doi.org/10.1371/journal.pone.0240562
Murthy KRS (translator). Vagbhata's Ashtanga Sangraha, Sutrasthana, chapter 18, verse no.17. 7th edition, Varanasi; Chaukhambha Krishnadas Academy; 2010; 340
Tak PP, Firestein GS. NF-κB: a key role in inflammatory diseases. The Journal of Clinical Investigation. 2001 Jan;107(1):7-11. Available from: https://doi.org/10.1172/JCI11830
Murthy KRS (translator). Vagbhata's Ashtanga Sangraha, Sutrasthana, chapter 18, verse no.12. 7th edition, Varanasi; Chaukhambha Krishnadas Academy; 2010; 338
Kumar S, Malhotra S, Prasad AK, Van der Eycken EV, Bracke ME, Stetler-Stevenson WG, et al. Anti-inflammatory and antioxidant properties of Piper species: a perspective from screening to molecular mechanisms. Current Topics in Medicinal Chemistry. 2015 May;15(9):886-893.Available from: https://doi.org/10.2174/1568026615666150220120651
Pradeep CR, Kuttan G. Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells. International Immunopharmacology. 2004 Dec;4(14):1795-1803. Availa-ble from: https://doi.org/10.1016/j.intimp.2004.08.005
Sharma R, Amin H, Galib, Prajapati PK. Antidiabetic claims of Tinospora cordifolia (Willd.) Miers: critical appraisal and role in therapy. Asian Pacific Journal of Tropical Bio-medicine. 2015 March;5(1):68-78. Available from: https://doi.org/10.1016/S2221-1691(15)30173-8
Kuan-Hong W, Bai-Zhou L. Plumbagin protects against hydrogen peroxide-induced neurotoxicity by modulating NF-κB and Nrf-2. Archives of Medical Science. 2018 Aug;14(5):1112-1118. Available from: https://doi.org/10.5114/aoms.2016.64768
Hei X, Xie M, Xu J, Li J, Liu T. β-Asarone exerts antioxidative effects on H2O2-stimulated PC12 cells by activating Nrf2/HO-1 pathway. Neurochemical Research. 2020 Jul;45(8):1953-1961. Available from: https://doi.org/10.1007/s11064-020-03060-9
Qin X, Meghana K, Sowjanya NL, Sushma KR, Krishna CG, Manasa J, et al. Embelin at-tenuates cisplatin-induced nephrotoxicity: involving inhibition of oxidative stress and in-flammation in addition with activation of Nrf-2/Ho-1 pathway. Biofactors. 2019 Mar;45(3):471-478. Available from: https://doi.org/10.1002/biof.1502
Dai S, Wang C, Zhao X, Ma C, Fu K, Liu Y, et al. Cucurbitacin B: A review of its pharma-cology, toxicity, and pharmacokinetics. Pharmacological Research. 2023 Jan;187:106587. Available from: https://doi.org/10.1016/j.phrs.2022.106587
Saha S, Alshammari A, Albekairi NA, Nahiyan ZT, Salman SM, Mondal KR, et al. Explor-ing the antioxidant and protective effects of Marsdenia thyrsiflora Hook.f. leaf extract against carbon tetrachloride-induced hepatic damage in rat models. Frontiers in Pharma-cology. 2024 Oct;15:1463922. Available from: https://doi.org/10.3389/fphar.2024.1463922
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Sachin Mangattu, Prof. Vd. Varsha R. Solanki, Dr Mukeshkumar Nariya, Dr Kalpesh Panara, Krunal Vadher
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors retain the copyright of their work and grant the Journal of Ayurveda and Holistic Medicine (JAHM) the right of first publication. All published articles are licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) license, which permits non-commercial sharing, use, distribution, and adaptation with proper attribution and the same license terms.
JAHM ensures free, irrevocable, worldwide access to its content. Users may copy, distribute, display, and share published works for non-commercial purposes with appropriate credit to the author(s) and the journal. Limited printed copies for personal, non-commercial use are allowed under the same license.
If a submission is not accepted for publication, the author(s) will be notified.
By submitting, authors confirm that the work is original, that all listed authors have contributed and approved it, and that it does not infringe any third-party rights or duplicate work submitted elsewhere.
