Role of Curcumin in Prevention of NAFLD Pathogenesis: Insights into Key Metabolic and Inflammatory Signaling Pathways
DOI:
https://doi.org/10.32350/sir.102.01Keywords:
inflammation, liver, non-alcoholic fatty liver disease, treatment strategiesAbstract
Non-alcoholic fatty liver disease (NAFLD), characterized by an elevated level of lipid accumulation in the liver, is the most widespread form of hepatic disorders, affecting 32% of the global population. In certain people, NAFLD may progress to the more advanced form, NASH (reversible), by developing inflammation and, in some cases, liver cirrhosis (irreversible). In turn, both NASH and cirrhotic livers have an increased chance of developing hepatocellular carcinoma (HCC) within the affected parenchyma. NAFLD resulting from nutrient overload and a sedentary lifestyle has a complex pathogenesis, including metabolic dysfunctions such as insulin resistance, atherosclerosis, obesity, dyslipidemia, and hypertension, leading to oxidative stress, endoplasmic reticulum (ER) stress, and inflammatory response, consequently causing liver injury and inflammation. NAFLD is predicted to become the most common indication for liver transplantation by 2030. Currently, lifestyle modification strategies with few pharmacological options are available to control the progression of this disease. A few drugs resmetirom (FDA approved), statins, metformin and fibrates, are currently in the market, but they have notable side effects (osteoporosis and secondary infections). Hence, there is a dire need for a novel drug candidate with high efficiency and few side effects. This review focuses on the therapeutic potential of curcumin, extracted from Curcuma longa, in preventing and modulating the key pathways involved in the pathogenesis of NAFLD as an innovative treatment candidate. We did a comprehensive and collective analysis of the available literature to create a single document covering all the pathogenic aspects of NAFLD and explore the treatment strategies using curcumin. It should be noted that the current data on curcumin is predominantly derived from preclinical sources such as in-vitro, animal and in-silico studies, with human trial evidences on curcumin remaining comparatively limited.
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References
1. Zhang Y, Luo M, Ming Y. Global burden of cirrhosis and other chronic liver diseases caused by specific etiologies from 1990 to 2021. BMC gastroenterology. 2025;25(1):641.
2. Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 2021;184(10):2537-2564.
3. Riazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. The lancet gastroenterology & hepatology. 2022;7(9):851-861.
4. SUKARE JG. PATHOLOGY OF EXPERIMENTALLY INDUCED FATTY LIVER DISEASE IN CHICKEN. MAHARASHTRA ANIMAL AND FISHERY SCIENCES UNIVERSITY; 2023.
5. Bessone F, Razori MV, Roma MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cellular and molecular life sciences. 2019;76(1):99.
6. Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World journal of gastroenterology. 2018;24(30):3361.
7. Guo X, Yin X, Liu Z, Wang J. Non-alcoholic fatty liver disease (NAFLD) pathogenesis and natural products for prevention and treatment. International journal of molecular sciences. 2022;23(24):15489.
8. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37(4):917-923.
9. Pouwels S, Sakran N, Graham Y, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC endocrine disorders. 2022;22(1):63.
10. Idilman IS, Ozdeniz I, Karcaaltincaba M. Hepatic steatosis: etiology, patterns, and quantification. Elsevier; 2016:501-510.
11. Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. New England Journal of Medicine. 2024;390(6):497-509.
12. Ventura T. Madrigal Pharmaceuticals Reports Second-Quarter 2024 Financial Results and Provides Corporate Updates.
13. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. US Food and Drug Administration 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease
14. Byrne CD, Targher G. NAFLD: a multisystem disease. Journal of hepatology. 2015;62(1):S47-S64.
15. Sookoian S, Pirola CJ. Precision medicine in nonalcoholic fatty liver disease: new therapeutic insights from genetics and systems biology. Clinical and molecular hepatology. 2020;26(4):461.
16. Nobili V, Alisi A, Valenti L, Miele L, Feldstein AE, Alkhouri N. NAFLD in children: new genes, new diagnostic modalities and new drugs. Nature reviews Gastroenterology & hepatology. 2019;16(9):517-530.
17. Chen Q, Wang T, Li J, et al. Effects of natural products on fructose-induced nonalcoholic fatty liver disease (NAFLD). Nutrients. 2017;9(2):96.
18. Reimer KC, Wree A, Roderburg C, Tacke F. New drugs for NAFLD: lessons from basic models to the clinic. Hepatology international. 2020;14(1):8-23.
19. Afshari AR, Jalili-Nik M, Abbasinezhad-Moud F, et al. Anti-tumor effects of curcuminoids in glioblastoma multiforme: An updated literature review. Current medicinal chemistry. 2021;28(39):8116-8138.
20. Shakeri A, Cicero AF, Panahi Y, Mohajeri M, Sahebkar A. Curcumin: A naturally occurring autophagy modulator. Journal of Cellular Physiology. 2019;234(5):5643-5654.
This review describes curcumin as a regulator of autophagy and summarizes its effects on multiple molecular pathways involved in cellular homeostasis, inflammation, oxidative stress, and metabolic disorders. It can support discussion of autophagy as one of the mechanisms through which curcumin may exert hepatoprotective and metabolic effects.
21. Machado MV, Cortez-Pinto H. Non-alcoholic fatty liver disease: what the clinician needs to know. World journal of gastroenterology: WJG. 2014;20(36):12956.
22. Zechner R, Kienesberger PC, Haemmerle G, Zimmermann R, Lass A. Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores. Journal of lipid research. 2009;50(1):3-21.
23. Chen Z, Tian R, She Z, Cai J, Li H. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radical Biology and Medicine. 2020;152:116-141.
24. Ameer F, Scandiuzzi L, Hasnain S, Kalbacher H, Zaidi N. De novo lipogenesis in health and disease. Metabolism. 2014;63(7):895-902.
25. Begriche K, Igoudjil A, Pessayre D, Fromenty B. Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion. 2006;6(1):1-28.
26. Marra F, Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. Journal of hepatology. 2018;68(2):280-295.
27. Fan J-G, Kim S-U, Wong VW-S. New trends on obesity and NAFLD in Asia. Journal of hepatology. 2017;67(4):862-873.
28. Sakurai Y, Kubota N, Yamauchi T, Kadowaki T. Role of insulin resistance in MAFLD. International journal of molecular sciences. 2021;22(8):4156.
29. Basaranoglu M, Basaranoglu G, Sabuncu T, Sentürk H. Fructose as a key player in the development of fatty liver disease. World journal of gastroenterology: WJG. 2013;19(8):1166.
30. Todisco S, Santarsiero A, Convertini P, et al. PPAR Alpha as a Metabolic Modulator of the Liver: Role in the Pathogenesis of Nonalcoholic Steatohepatitis (NASH). Biology. 2022;11(5):792.
31. Li W, Cao T, Luo C, et al. Crosstalk between ER stress, NLRP3 inflammasome, and inflammation. Applied Microbiology and Biotechnology. 07/01 2020;104:1-12. doi:10.1007/s00253-020-10614-y
32. Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nature cell biology. 03/01 2011;13:184-90. doi:10.1038/ncb0311-184
33. van Meer G. Membrane lipids, where they are and how they behave: Sphingolipids on the move. The FASEB Journal. 04/01 2010;24doi:10.1096/fasebj.24.1_supplement.312.1
34. Pan D, Yang Y, Nong A, Tang Z, Li QX. GRP78 Activity Moderation as a Therapeutic Treatment against Obesity. International Journal of Environmental Research and Public Health. 2022;19(23):15965.
35. Flamment M, Kammoun HL, Hainault I, Ferré P, Foufelle F. Endoplasmic reticulum stress: a new actor in the development of hepatic steatosis. Current Opinion in Lipidology. 2010;21:239–246.
36. Puri P, Mirshahi F, Natarajan R, Maher J, Kellum J, Sanyal A. Differential activation and dysregulation of unfolded protein response (UPR) in nonalcoholic fatty liver disease (NAFLD): Implications for pathogenesis. 2006:213A-213A.
37. Gentile C, Frye M, Pagliassotti M. Endoplasmic Reticulum Stress and the Unfolded Protein Response in Nonalcoholic Fatty Liver Disease. Antioxidants & Redox Signaling. 12/01 2010;15:505-521. doi:10.1089/ars.2010.3790
38. Rong L, Zou J, Ran W, et al. Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD). Review. Frontiers in Endocrinology. 2023-January-16 2023;Volume 13 - 2022doi:10.3389/fendo.2022.1087260
39. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016/08/01/ 2016;65(8):1038-1048. doi:https://doi.org/10.1016/j.metabol.2015.12.012
40. Abenavoli L, Larussa T, Corea A, et al. Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease. Nutrients. 2021;13(2):494.
This study discusses the role of dietary polyphenols in NAFLD prevention and management, including their antioxidant, anti-inflammatory, and metabolic effects. It provides broader evidence positioning curcumin within the larger class of plant-derived polyphenols investigated for NAFLD.
41. Basnet P, Skalko-Basnet N. Curcumin: an anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules. Jun 3 2011;16(6):4567-98. doi:10.3390/molecules16064567
This review describes curcumin as a regulator of autophagy and summarizes its effects on multiple molecular pathways involved in cellular homeostasis, inflammation, oxidative stress, and metabolic disorders. It can support discussion of autophagy as one of the mechanisms through which curcumin may exert hepatoprotective and metabolic effects.
42. Tuba E, Patricia H, Insa M A E, Dawn C, Anika E W, Gerald R. Curcumin—From Molecule to Biological Function. Angewandte Chemie International Edition. 2012 2012;51:5308-5332. doi:10.1002/anie.201107724
43. Ayati Z, Ramezani M, Amiri MS, et al. Ethnobotany, Phytochemistry and Traditional Uses of Curcuma spp. and Pharmacological Profile of Two Important Species (C. longa and C. zedoaria): A Review. Current pharmaceutical design. 2019;25(8):871-935. doi:10.2174/1381612825666190402163940
44. Lobo R, Prabhu KS, Shirwaikar A, Shirwaikar A. Curcuma zedoaria Rosc. (white turmeric): a review of its chemical, pharmacological and ethnomedicinal properties. The Journal of pharmacy and pharmacology. Jan 2009;61(1):13-21. doi:10.1211/jpp/61.01.0003
45. Ashraf A, Rather SA, Mehraj M. “Evaluation of Curcuma zedoaria Rosc. in the management of non-alcoholic fatty liver Disease: A Randomized, single blind, controlled trial”. Arab Journal of Gastroenterology. 2025/02/01/ 2025;26(1):112-119. doi:https://doi.org/10.1016/j.ajg.2025.01.004
46. Jarhahzadeh M, Alavinejad P. The effect of turmeric on lipid profile, malondialdehyde, liver echogenicity and enzymes among patients with nonalcoholic fatty liver disease: a randomized double blind clinical trial. Oct 18 2021;13(1):112. doi:10.1186/s13098-021-00731-7
47. Rahmani S, Asgary S, Askari G, et al. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial. Phytotherapy research : PTR. Sep 2016;30(9):1540-8. doi:10.1002/ptr.5659
48. Saadati S, Sadeghi A, Mansour A, et al. Curcumin and inflammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial. Jul 25 2019;19(1):133. doi:10.1186/s12876-019-1055-4
This clinical study specifically investigates curcumin in relation to inflammatory processes in NAFLD. It is particularly useful for supporting the anti-inflammatory component of the proposed mechanism of curcumin in NAFLD and for connecting experimental findings involving inflammatory mediators with human evidence.
49. Panknin TM, Howe CL, Hauer M, Bucchireddigari B, Rossi AM, Funk JL. Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Int J Mol Sci. Feb 24 2023;24(5)doi:10.3390/ijms24054476
50. Jafari A, Abbastabar M, Alaghi A, Heshmati J. Curcumin on Human Health: A Comprehensive Systematic Review and Meta-Analysis of 103 Randomized Controlled Trials. Dec 2024;38(12):6048-6061. doi:10.1002/ptr.8340
This systematic review and meta-analysis synthesizes evidence from 103 randomized controlled trials examining curcumin and human health outcomes. It provides high-level clinical evidence for the biological effects of curcumin and can strengthen the translational rationale of the manuscript while acknowledging that clinical effects vary according to disease, formulation, dose, and study design.
51. Zingg J-M, Hasan S, Azzi A, Meydani M. Molecular mechanisms of hypolipidemic effects of curcumin. The FASEB Journal. 04/01 2013;27doi:10.1096/fasebj.27.1_supplement.637.37
52. Liu S, Liu J, He L, et al. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. Molecules. 2022;27(14):4400.
53. Mahmoudi A, Butler AE, Majeed M, Banach M, Sahebkar A. Investigation of the Effect of Curcumin on Protein Targets in NAFLD Using Bioinformatic Analysis. Nutrients. 2022;14(7):1331.
This reference is highly relevant to the mechanistic and computational component of the manuscript. The study investigates protein targets associated with the effects of curcumin in NAFLD using bioinformatic approaches. It can support the rationale for exploring molecular targets and signaling pathways through computational approaches such as network pharmacology and molecular docking.
54. Wang C, Wang P, Chen W, Bai Y. Mechanisms of Gynostemma pentaphyllum against non-alcoholic fibre liver disease based on network pharmacology and molecular docking. Journal of Cellular and Molecular Medicine. 2022;26(13):3760-3771. doi:https://doi.org/10.1111/jcmm.17410
55. Elzoheiry A, Ayad E, Omar N, Elbakry K, Hyder A. Anti-liver fibrosis activity of curcumin/chitosan-coated green silver nanoparticles. Scientific Reports. 2022/11/01 2022;12(1):18403. doi:10.1038/s41598-022-23276-9
56. Han Q, Zhu J, Zhang P. Mechanisms of main components in Curcuma longa L. on hepatic fibrosis based on network pharmacology and molecular docking: A review. Medicine. 07/21 2023;102:e34353. doi:10.1097/MD.0000000000034353
57. Jadhav PA, Thomas AB, Pathan MK, Chaudhari SY, Wavhale RD, Chitlange SS. Unlocking the therapeutic potential of unexplored phytocompounds as hepatoprotective agents through integration of network pharmacology and in-silico analysis. Scientific Reports. 2025/03/11 2025;15(1):8425. doi:10.1038/s41598-025-92868-y
58. Prakash S, Kamalnath S, Antonisamy A, Marimuthu S, Malayandi S. In Silico Molecular Docking of Phytochemicals for Type 2 Diabetes Mellitus Therapy: A Network Pharmacology Approach. 01/01 2023;12:372-387. doi:10.22088/IJMCM.BUMS.12.4.372
59. Khan A, Sayaf AM, Alshammarri A, et al. Network Pharmacology Integrated With Quantum-Polarized Ligand Docking and Molecular Simulation Revealed the Anti-Diabetic Potential of Curcumin. ChemistrySelect. 2024;9(37):e202402379. doi:https://doi.org/10.1002/slct.202402379
60. Pokhrel A, Chong K, Tayara H. Therapeutic Potential of Curcuminoids in Type 2 Diabetes Mellitus (T2DM): Insights from Network Pharmacology, Molecular Docking, and Dynamics Simulations. Food Bioscience. 03/01 2025;68:106406. doi:10.1016/j.fbio.2025.106406
61. Rahmani B, Akbari H, Esmaeili H, Solaimanian S, Mobasheri M, Shiri-Shahsavar MR. Discovering bioactive pharmaceuticals from natural products for type 2 diabetes mellitus using network pharmacology, molecular docking, and molecular dynamics. Scientific Reports. 2025/12/05 2025;15(1):43205. doi:10.1038/s41598-025-27173-9
62. Shang CZaJ. Network pharmacology combined with molecular docking to investigate the potential role of curcumin targeting TGR5 to modulate the GLP-1 pathway in T2DM with obesity. Pakistan Journal of Pharmaceutical Sciences. 2026;39(09)doi:doi.org/10.36721/PJPS.2026.39.9.243.1
63. Gong X, Xue D, Meng H, et al. Curcumin attenuates LPS-induced inflammation in RAW 264.7 cells: A multifaceted study integrating network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation. 2025;20(10):e0335139. doi:10.1371/journal.pone.0335139
64. Wang L, Zhang B, Huang F, Liu B, Xie Y. Curcumin inhibits lipolysis via suppression of ER stress in adipose tissue and prevents hepatic insulin resistance[S]. Journal of Lipid Research. 2016/07/01/ 2016;57(7):1243-1255. doi:https://doi.org/10.1194/jlr.M067397
65. Tanase DM, Gosav EM, Costea CF, et al. The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD). Journal of Diabetes Research. 2020;2020(1):3920196. doi:https://doi.org/10.1155/2020/3920196
66. Khan H, Ullah H, Nabavi S. Mechanistic insights of hepatoprotective effects of curcumin: Therapeutic updates and future prospects. Food and Chemical Toxicology. 12/01 2018;124doi:10.1016/j.fct.2018.12.002
This review focuses specifically on the hepatoprotective mechanisms of curcumin and discusses molecular pathways through which curcumin may protect against liver injury. It is highly suitable for supporting the manuscript’s mechanistic discussion of antioxidant, anti-inflammatory, metabolic, and hepatoprotective actions.
67. Copley J, Braun M, Fromkin B, et al. Beneficial Effects of the Bioflavonoids Curcumin and Quercetin on Early Function in Cadaveric Renal Transplantation: A Randomized Placebo Controlled Trial. Transplantation. 2005/12/15 2005;80(11):1556-1559. doi:10.1097/01.tp.0000183290.64309.21
68. Jagetia GC, Rajanikant GK. Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation. Antioxidants. 2015;4(1):25-41.
69. Ferreira VH, Nazli A, Dizzell SE, Mueller K, Kaushic C. The Anti-Inflammatory Activity of Curcumin Protects the Genital Mucosal Epithelial Barrier from Disruption and Blocks Replication of HIV-1 and HSV-2. PloS one. 2015;10(4):e0124903. doi:10.1371/journal.pone.0124903
70. Inzaugarat ME, De Matteo E, Baz P, et al. New evidence for the therapeutic potential of curcumin to treat nonalcoholic fatty liver disease in humans. PloS one. 2017;12(3):e0172900. doi:10.1371/journal.pone.0172900
This study provides human evidence supporting the potential therapeutic effects of curcumin in NAFLD. It is useful for strengthening the translational section of the manuscript and for demonstrating that the proposed hepatoprotective effects of curcumin are supported not only by experimental models but also by clinical observations.
71. Afrin R, Arumugam S, Rahman A, et al. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation. International Immunopharmacology. 2017/03/01/ 2017;44:174-182. doi:https://doi.org/10.1016/j.intimp.2017.01.016
72. Kheradpezhouh E, Barritt GJ, Rychkov GY. Curcumin inhibits activation of TRPM2 channels in rat hepatocytes. Redox Biology. 2016/04/01/ 2016;7:1-7. doi:https://doi.org/10.1016/j.redox.2015.11.001
73. Yan C, Zhang Y, Zhang X, Aa J, Wang G, Xie Y. Curcumin regulates endogenous and exogenous metabolism via Nrf2-FXR-LXR pathway in NAFLD mice. Biomedicine & Pharmacotherapy. 2018/09/01/ 2018;105:274-281. doi:https://doi.org/10.1016/j.biopha.2018.05.135
74. Kawaguchi T, Tsutsumi T, Nakano D, Torimura T. MAFLD: Renovation of clinical practice and disease awareness of fatty liver. Hepatology Research. 2022;52(5):422-432. doi:https://doi.org/10.1111/hepr.13706
75. He Y, Wang H, Lin S, et al. Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade. Biomedicine & Pharmacotherapy. 2023/09/01/ 2023;165:115279. doi:https://doi.org/10.1016/j.biopha.2023.115279
76. Xiong Y, Lu H, Xu H. Galangin Reverses Hepatic Fibrosis by Inducing HSCs Apoptosis via the PI3K/Akt, Bax/Bcl-2, and Wnt/β-Catenin Pathway in LX-2 Cells. Biological and Pharmaceutical Bulletin. 2020;43(11):1634-1642. doi:10.1248/bpb.b20-00258
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