Author(s): Sajja Keerthi Vathsalya, A. Gnanavel, N. Hima Bindu, S. Saravana Kumar, B. Naveen Kumar

Email(s): keerthi.vathsalyasajja@gmail.com , dragnanavel@gmail.com , nalluribindu@gmail.com , saraanatomy@gmail.com , bandarupallinaveen@gmail.com

DOI: 10.52711/0974-360X.2025.00655   

Address: Sajja Keerthi Vathsalya1, A. Gnanavel1, N. Hima Bindu2, S. Saravana Kumar1, B. Naveen Kumar2
1Meenakshi Medical College Hospital and Research Institute, Enathur, Tamil Nadu.
2Mamata Academy of Medical Sciences, Bachupally Medchal-Malkajgiri (District) Hyderabad - 500 118 Telangana State, India.
*Corresponding Author

Published In:   Volume - 18,      Issue - 9,     Year - 2025


ABSTRACT:
Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders not linked to excessive alcohol consumption. It ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma (HCC). As NAFLD is closely associated with metabolic dysregulation, a shift in terminology to metabolic associated fatty liver disease (MAFLD) has been suggested. Despite its global rise in prevalence, there are currently no pharmacological treatments for NAFLD, necessitating exploration of therapeutic pathways. Objectives: This review aims to systematically analyze current therapeutic options for NAFLD, including allopathic and herbal remedies, to identify potential future directions for drug discovery. Emphasis is placed on understanding marketed hepatoprotective and anti-obesity drugs, exploring the integration of traditional Ayurvedic approaches with modern allopathic therapies. Methods: A comprehensive search was conducted across multiple databases, including PubMed, Scopus, Web of Science, and clinical trial registries. The search terms used were "NAFLD," "NASH," "therapeutic discovery," "drug development," "hepatoprotective drugs," "anti-inflammatory drugs," "herbal medicine," "Ayurvedic medicine," and "anti-obesity drugs." The search was limited to studies published in English between 2000 and 2024 to capture recent advancements in the field. Additional manual searches were performed by reviewing the reference lists of relevant studies and reviewing abstracts from major hepatology and pharmacology conferences. Results: The analysis highlights the absence of universally effective pharmacological treatments for NAFLD. While current allopathic drugs target specific pathways such as inflammation and fibrosis, their efficacy remains limited. Herbal and Ayurvedic treatments, though widely marketed as hepatoprotective, lack sufficient clinical validation. Combining allopathic and traditional approaches may offer a promising avenue for developing comprehensive treatment strategies. Conclusions: The increasing prevalence of NAFLD calls for innovative therapeutic strategies that bridge the gap between traditional medicine and modern drug discovery. Future research should focus on targeted anti-inflammatory therapies and multi-faceted treatment approaches that incorporate both allopathic and herbal/Ayurvedic remedies. Such integration could accelerate the discovery of effective treatments, improving patient outcomes in NAFLD management.


Cite this article:
Sajja Keerthi Vathsalya, A. Gnanavel, N. Hima Bindu, S. Saravana Kumar, B. Naveen Kumar. A Comprehensive Systematic Review on Therapeutic Discovery of NAFLD Drugs. Research Journal of Pharmacy and Technology. 2025;18(9):4564-0. doi: 10.52711/0974-360X.2025.00655

Cite(Electronic):
Sajja Keerthi Vathsalya, A. Gnanavel, N. Hima Bindu, S. Saravana Kumar, B. Naveen Kumar. A Comprehensive Systematic Review on Therapeutic Discovery of NAFLD Drugs. Research Journal of Pharmacy and Technology. 2025;18(9):4564-0. doi: 10.52711/0974-360X.2025.00655   Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-9-75


REFERENCES:
1.    Hu C, Gao D, Li D, Zhou D, Zhang L. Chinese- and French-Manufactured Immediate-Release Glucophage® Bioequivalence: A Randomized, Open-Label, Crossover Study. Drugs R D. 2022;  22(4): 301–9. 
2.    Adams LA, Lymp JF, Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study. Gastroenterology. 2005; 129(1): 113–21. 
3.    Gofton C, Upendran Y, Zheng MH, George J. MAFLD: How is it different from NAFLD? Clinical and Molecular Hepatology. 2023; 29(Suppl):17–31. 
4.    Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, Caballeria J, et al. Modeling NAFLD disease burden in China. Journal of Hepatology. 2018; 69(4): 896–904. 
5.    Younossi ZM, Stepanova M, Ong J, Trimble G, AlQahtani S, Younossi I, et al. Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in the United States. Clinical Gastroenterology and Hepatology. 2021; 19(3): 580–9. 
6.    Xu Y, Guo W, Zhang C, Chen F, Tan HY, Li S, et al. Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application. Front Pharmacol [Internet]. 2020; May 12 [cited 2024 Jul 12];11. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00601/full
7.    Singhal P, Nesari T, Gupta GS. Efficacy of herbomineral compounds and pathya (Ayurvedic dietary regime and physical exercise) in the management of Yakṛt Roga (Non-alcoholic fatty liver disease). Anc Sci Life. 2015; 34(4): 216–22. 
8.    Tarapure S, Tubaki BR, Khot S. Elastographic liver evaluation of Katukyadi churna in the management of Non-Alcoholic Steatohepatitis (NASH) – A single arm clinical trial. J Ayurveda Integr Med. 2021; 12(1): 136–42. 
9.    Sahu AK, Upadhyay A, Bhakuni H, Attanayake AMHS, Sharma P. Effect of Ayurveda interventions in non-alcoholic grade II fatty liver associated with obesity – A case report. J Ayurveda Integr Med. 2022; 13(3): 100605. 
10.    Kamata S, Honda A, Ishii I. Current Clinical Trial Status and Future Prospects of PPAR-Targeted Drugs for Treating Nonalcoholic Fatty Liver Disease. Biomolecules. 2023; Aug; 13(8): 1264. 
11.    Lange NF, Graf V, Caussy C, Dufour JF. PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients. Int J Mol Sci. 2022; 23(8): 4305. 
12.    Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016; 65(8): 1038–48. 
13.    Song C, Long X, He J, Huang Y. Recent evaluation about inflammatory mechanisms in nonalcoholic fatty liver disease. Front Pharmacol [Internet]. 2023 Mar 16 [cited 2024 Jul 13];14. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1081334/full
14.    Du J, Ma YY, Yu CH, Li YM. Effects of pentoxifylline on nonalcoholic fatty liver disease: A meta-analysis. World J Gastroenterol. 2014; 20(2): 569–77. 
15.    Chang Y, Li H. Hepatic Antifibrotic Pharmacotherapy: Are We Approaching Success? Journal of Clinical and Translational Hepatology. 2020; 8(2): 222–9. 
16.    Kokkorakis M, Boutari C, Hill MA, Kotsis V, Loomba R, Sanyal AJ, et al. Resmetirom, the first approved drug for the management of metabolic dysfunction-associated steatohepatitis: Trials, opportunities, and challenges. Metabolism - Clinical and Experimental. 2024; 154. 
17.    Xu ST, Jin HW, Jin X, Xu BX, Zhang Y, Xie T, et al. Development and validation for bioanalysis of VK2809, its active metabolite VK2809A and glutathione-conjugated metabolite MB06588 in rat liver using LC-MS/MS. Journal of Pharmaceutical and Biomedical Analysis. 2023; 234: 115595. 
18.    Liu L, Yan H, Xia M, Zhao L, Lv M, Zhao N, et al. Efficacy of exenatide and insulin glargine on nonalcoholic fatty liver disease in patients with type 2 diabetes. Diabetes/Metabolism Research and Reviews. 2020; 36(5): 3292. 
19.    Lee HA, Kim HY. Therapeutic Mechanisms and Clinical Effects of Glucagon-like Peptide 1 Receptor Agonists in Nonalcoholic Fatty Liver Disease. International Journal of Molecular Sciences. 2023; Jan; 24(11): 9324. 
20.    Li Z, Lin B, Lin G, Wu Y, Jie Y, Li X, et al. Circulating FGF19 closely correlates with bile acid synthesis and cholestasis in patients with primary biliary cirrhosis. PLoS ONE. 2017; 12(6): 0178580. 
21.    Ali AH, Lindor KD. Obeticholic acid for the treatment of primary biliary cholangitis. Expert Opinion on Pharmacotherapy. 2016; 17(13): 1809–15. 
22.    Harrison SA, Bashir MR, Lee KJ, Shim-Lopez J, Lee J, Wagner B, et al. A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis. Journal of Hepatology. 2021; 75(1): 25–33. 
23.    Morrison A, Elgendy B. Tailoring FXR Modulators for Intestinal Specificity: Recent Progress and Insights. Molecules. 2024; 29(9): 9. 
24.    Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, et al. Cilofexor. a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase. 2020; 72(1): 58–71. 
25.    Androutsakos T, Nasiri-Ansari N, Bakasis AD, Kyrou I, Efstathopoulos E, Randeva HS, et al. SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection. International Journal of Molecular Sciences. 2022; 23(6): 3107. 
26.    Ong Lopez AMC, Pajimna JAT. Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: An updated systematic review and meta-analysis. Scientific Reports. 2024; 14(1): 2122. 
27.    Guo J, Shi CX, Zhang QQ, Deng W, Zhang LY, Chen Q, et al. Interventions for non-alcoholic liver disease: A gut microbial metabolites perspective. Therapeutic Advances in Gastroenterology. 2022; 15: 17562848221138676. 
28.    Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis. New England Journal of Medicine. 2010; 362(18): 1675–85. 
29.    Cusi K, Orsak B, Bril F, Lomonaco R, Hecht J, Ortiz-Lopez C, et al. Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus. Ann Intern Med. 2016; 165(5): 305–15. 
30.    Wang Z, Du H, Zhao Y, Ren Y, Ma C, Chen H, et al. Response to pioglitazone in non-alcoholic fatty liver disease patients with vs. without type 2 diabetes: A meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2023; 14: 1111430. 
31.    Saryusz-Wolska M, Szymańska-Garbacz E, Jabłkowski M, Białkowska J, Pawłowski M, Kwiecińska E, et al. Rosiglitazone treatment in nondiabetic subjects with nonalcoholic fatty liver disease. Pol Arch Med Wewn. 2011; 121(3): 61–6. 
32.    Batatinha HAP, Lima EA, Teixeira AAS, Souza CO, Biondo LA, Silveira LS, et al. Association Between Aerobic Exercise and Rosiglitazone Avoided the NAFLD and Liver Inflammation Exacerbated in PPAR-α Knockout Mice. J Cell Physiol. 2017; May; 232(5): 1008–19. 
33.    Zarganes-Tzitzikas T, Neochoritis CG, Dömling A. Atorvastatin (Lipitor) by MCR. ACS Med Chem Lett. 2019; Mar 14; 10(3): 389–92. 
34.    Rojas Á, Lara-Romero C, Muñoz-Hernández R, Gato S, Ampuero J, Romero-Gómez M. Emerging pharmacological treatment options for MAFLD. Ther Adv Endocrinol Metab. 2022; Dec 10;13: 20420188221142452. 
35.    Vell MS, Creasy KT, Scorletti E, Seeling KS, Hehl L, Rendel MD, et al. Omega-3 intake is associated with liver disease protection. Front Public Health [Internet]. 2023 Jul 19 [cited 2024 Jul 13];11. Available from: https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1192099/full
36.    Ali AH, Lindor KD. Obeticholic acid for the treatment of primary biliary cholangitis. Expert Opin Pharmacother. 2016; 17(13): 1809–15. 
37.    Ong Lopez AMC, Pajimna JAT. Efficacy of sodium glucose cotransporter 2 inhibitors on hepatic fibrosis and steatosis in non-alcoholic fatty liver disease: an updated systematic review and meta-analysis. Sci Rep. 2024; 14(1): 2122. 
38.    Aso Y, Kato K, Sakurai S, Kishi H, Shimizu M, Jojima T, et al. Impact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease. International Journal of Clinical Practice. 2019; 73(5): e13335. 
39.    Zelber-Sagi S, Kessler A, Brazowsky E, Webb M, Lurie Y, Santo M, et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006; 4(5): 639–44. 
40.    Pan CS, Stanley TL. Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review. Front Endocrinol (Lausanne). 2020; 21; 11: 70. 
41.    Dufour JF, Anstee QM, Bugianesi E, Harrison S, Loomba R, Paradis V, et al. Current therapies and new developments in NASH. Gut. 2022; 71(10): 2123–34. 

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