Skip to main content

Advertisement

SpringerLink
Log in

Functional Food Chemical Ingredient Strategies for Non-alcoholic Fatty Liver Disease (NAFLD) and Hepatic Fibrosis: Chemical Properties, Health Benefits, Action, and Application

  • REVIEW
  • Published:
Current Nutrition Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The liver is an important digestive gland in the body. Lifestyle and dietary habits are increasingly damaging our liver, leading to various diseases and health problems. Non-alcoholic fatty liver disease (NAFLD) has become one of the most serious liver disease problems in the world. Diet is one of the important factors in maintaining liver health. Functional foods and their components have been identified as novel sources of potential preventive agents in the prevention and treatment of liver disease in daily life. However, the effects of functional components derived from small molecules in food on different types of liver diseases have not been systematically summarized.

Recent Findings

The components and related mechanisms in functional foods play a significant role in the development and progression of NAFLD and liver fibrosis. A variety of structural components are found to treat and prevent NAFLD and liver fibrosis through different mechanisms, including flavonoids, alkaloids, polyphenols, polysaccharides, unsaturated fatty acids, and peptides. On the other hand, the relevant mechanisms include oxidative stress, inflammation, and immune regulation, and a large number of literature studies have confirmed a close relationship between the mechanisms.

Summary

The purpose of this article is to examine the current literature related to functional foods and functional components used for the treatment and protection against NAFLD and hepatic fibrosis, focusing on chemical properties, health benefits, mechanisms of action, and application in vitro and in vivo. The roles of different components in the biological processes of NAFLD and liver fibrosis were also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as:     • Of importance     •• Of major importance

  1. Emir M, Dimitri PM, Christos M. Non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome and their association with vascular risk. Metabolism. 2021;119: 154770.

    Article  Google Scholar 

  2. Hsieh YC, Joo SK, Koo BK, Lin HC, Lee DH, Chang MS, et al. Myosteatosis, but not sarcopenia, predisposes NAFLD subjects to early steatohepatitis and fibrosis progression. Clin Gastroenterol Hepatol. 2023;21(2):388–97.

    Article  CAS  PubMed  Google Scholar 

  3. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2017;15(1):11–20.

    Article  PubMed  Google Scholar 

  4. Anstee, Quentin M, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10(6):330–44.

  5. Yang Q, Zhang L, Li Q, Gu M, Qu Q, Yang X, et al. Characterization of microbiome and metabolite analyses in patients with metabolic associated fatty liver disease and type II diabetes mellitus. BMC Microbiol. 2022;22(1):105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kleiner, David E, Makhlouf HR. Histology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in adults and children. Clin Liver Dis. 2015;20(2):293–312.

  7. Gawrieh S, Chalasani N. Emerging treatments for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis. 2017;22(1):189–99.

    Article  PubMed  Google Scholar 

  8. Kleiner DE, Bedossa P. Liver histology and clinical trials for nonalcoholic steatohepatitis-perspectives from 2 pathologists. Gastroenterology. 2015;149(6):1305–8.

    Article  PubMed  Google Scholar 

  9. Tilg H, Moschen AR. IL-1 cytokine family members and NAFLD: neglected in metabolic liver inflammation. J Hepatol. 2011;55(5):960–2.

    Article  CAS  PubMed  Google Scholar 

  10. Bhowmick S, Singh V, Jash S, Lal M, Sinha RS. Mitochondrial metabolism and calcium homeostasis in the development of NAFLD leading to hepatocellular carcinoma. Mitochondrion. 2021;58:24–37.

    Article  CAS  PubMed  Google Scholar 

  11. Zarghamravanbakhsh P, Frenkel M, Poretsky L. Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD). Metabolism Open. 2021;12: 100149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gong F, Zheng KI, Tang L, Li G, Rios RS, Huang O, et al. Glycemic control predicts the risk of hepatic fibrosis in biopsy-proven NAFLD: a possible mediating role for leukemia inhibitory factor? iLiver. 2022;1(1):30–34.

  13. Zambrano-Huailla R, Guedes L, Stefano JT, Arrais DS, Arthur A, Marciano S, et al. Diagnostic performance of three non-invasive fibrosis scores (Hepamet, FIB-4, NAFLD fibrosis score) in NAFLD patients from a mixed Latin American population. Ann Hepatol. 2020;19(6):622–6.

    Article  CAS  PubMed  Google Scholar 

  14. Xiong Y, Wen S, Li Y, Wei Y, Fang B, Li C, et al. Comprehensive analysis of transcriptomics and metabolomics to illustrate the underlying mechanism of helenalin against hepatic fibrosis. Eur J Pharmacol. 2022;919: 174770.

    Article  CAS  PubMed  Google Scholar 

  15. Hurrell T, Kastrinou-Lampou V, Fardellas A, Hendriks DF, Nordling A, Johansson I, et al. Human liver spheroids as a model to study aetiology and treatment of hepatic fibrosis. Cells. 2020;9(4):964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. •• Gao L, Ma J, Fan Y, Zhang Y, Ge R, Tao X, et al. Lycium barbarum polysaccharide combined with aerobic exercise ameliorated nonalcoholic fatty liver disease through restoring gut microbiota, intestinal barrier and inhibiting hepatic inflammation. Int J Biol Macromol. 2021;183:1379–92. Research has revealed that goji berry polysaccharides can be considered as a prebiotic formulation, and LBP+AE may be a promising method for treating NAFLD, as it can maintain the balance of intestinal microbiota, thereby restoring the intestinal barrier and benefiting the liver.

  17. Zou C, Fang Y, Lin N, Liu H. Polysaccharide extract from pomelo fruitlet ameliorates diet-induced nonalcoholic fatty liver disease in hybrid grouper (Epinephelus lanceolatus x Epinephelus fuscoguttatus). Fish Shellfish Immunol. 2021;119:114–27.

    Article  CAS  PubMed  Google Scholar 

  18. Wang P, Zhang X, Luo P, Jiang X, Zhang P, Guo J, et al. Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling. Nat Commun. 2016;7:10592.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  19. Sun W, Li X, Dou H, Wang X, Li J, Shen L, et al. Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota. Cell Rep. 2021;36(9): 109641.

    Article  CAS  PubMed  Google Scholar 

  20. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology. Br J Clin Pharmacol. 2012;75(3):645–62.

    Article  Google Scholar 

  21. Kaliannan K, Li XY, Wang B, Pan Q, Chen C, Hao L, et al. Multi-omic analysis in transgenic mice implicates omega-6/omega-3 fatty acid imbalance as a risk factor for chronic disease. Commun Biol. 2019;2(1):1–18.

    Article  CAS  Google Scholar 

  22. Shapiro H, Tehilla M, Attal-Singer J, Bruck R, Luzzatti R, Singer P. The therapeutic potential of long-chain omega-3 fatty acids in nonalcoholic fatty liver disease. Clin Nutr. 2010;30(1):6–19.

    Article  PubMed  Google Scholar 

  23. Sangouni AA, Orang Z, Mozaffari-Khosravi H. Effect of omega-3 supplementation on cardiometabolic indices in diabetic patients with non-alcoholic fatty liver disease: a randomized controlled trial. BMC Nutr. 2021;7(1):86.

    Article  PubMed  PubMed Central  Google Scholar 

  24. •• Batista ES, Da SR, Munoz VR, Jesus JS, Vasconcelos MM, Da CD, et al. Omega-3 mechanism of action in inflammation and endoplasmic reticulum stress in mononuclear cells from overweight non-alcoholic fatty liver disease participants: study protocol for the “Brazilian Omega Study” (BROS)-a randomized controlled trial. Trials. 2021;22(1):927. This study shows that inflammation and weakened ER stress signaling pathways in overweight and NAFLD participants will be supplemented by binding to the GPR120 receptor ω 3 to achieve.

  25. Yan J, Guan B, Gao H, Peng X. Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Medicine. 2018;97: e12271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Elhessy HM, Eltahry H, Erfan OS, Mahdi MR, Hazem NM, El-Shahat MA. Evaluation of the modulation of nitric oxide synthase expression in the cerebellum of diabetic albino rats and the possible protective effect of ferulic acid. Acta Histochem. 2020;122(8): 151633.

    Article  CAS  PubMed  Google Scholar 

  27. Yuan J, Ge K, Mu J, Rong J, Zhang L, Wang B, et al. Ferulic acid attenuated acetaminophen-induced hepatotoxicity though down-regulating the cytochrome P 2E1 and inhibiting toll-like receptor 4 signaling-mediated inflammation in mice. Am J Transl Res. 2016;8(10):4205–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Luo Z, Li M, Yang Q, Zhang Y, Liu F, Gong L, et al. Ferulic acid prevents nonalcoholic fatty liver disease by promoting fatty acid oxidation and energy expenditure in C57BL/6 mice fed a high-fat diet. Nutrients. 2022;14(12):2530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shi X, Zhou X, Chu X, Wang J, Xie B, Ge J, et al. Allicin improves metabolism in high-fat diet-induced obese mice by modulating the gut microbiota. Nutrients. 2019;11(12):2019.

    Article  Google Scholar 

  30. Tirkey N, Pilkhwal S, Kuhad A, Chopra K. Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney. BMC Pharmacol. 2005;5.

  31. Chen H, Nie T, Zhang P, Ma J, Shan. Hesperidin attenuates hepatic lipid accumulation in mice fed high-fat diet and oleic acid induced HepG2 via AMPK activation. Life Sci. 2022;296:120428.

  32. Kong R, Wang N, Luo H, Lu J. Hesperetin mitigates bile duct ligation-induced liver fibrosis by inhibiting extracellular matrix and cell apoptosis via the TGF-β1/Smad pathway. Curr Mol Med. 2018;18(1):15–24.

    Article  CAS  PubMed  Google Scholar 

  33. El-Sisi AEE, Sokar SS, Shebl AM, Mohamed DZ. Antifibrotic effect of diethylcarbamazine combined with hesperidin against ethanol induced liver fibrosis in rats. Biomed Pharmacother. 2017;89:1196–206.

    Article  CAS  PubMed  Google Scholar 

  34. Morsy MA, Nair AB. Prevention of rat liver fibrosis by selective targeting of hepatic stellate cells using hesperidin carriers. Int J Pharm. 2018;552:241–50.

    Article  CAS  PubMed  Google Scholar 

  35. Nasehi Z, Kheiripour N, Taheri MA, Ardjmand A, Jozi F, Shahaboddin ME. Efficiency of hesperidin against liver fibrosis induced by bile duct ligation in rats. Biomed Res Int. 2023;2023:5444301.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KD. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol. 2001;96(9):2711–7.

    Article  CAS  PubMed  Google Scholar 

  37. Bingul I, Basaran-Kucukgergin C, Aydin AF, Coban J, Dogan-Ekici I, Dogru-Abbasoglu S, et al. Betaine treatment decreased oxidative stress, inflammation, and stellate cell activation in rats with alcoholic liver fibrosis. Environ Toxicol Pharmacol. 2016;45:170–8.

    Article  CAS  PubMed  Google Scholar 

  38. Mo C, Xie S, Zeng T, Lai Y, Huang S, Zhou C, et al. Ginsenoside-Rg1 acts as an IDO1 inhibitor, protects against liver fibrosis via alleviating IDO1-mediated the inhibition of DCs maturation. Phytomedicine. 2021;84: 153524.

    Article  CAS  PubMed  Google Scholar 

  39. Yuan S, Dong M, Zhang H, Jiang X, Yan C, Ye R, et al. Ginsenoside PPD inhibit the activation of HSCs by directly targeting TGFβR1. Int J Biol Macromol. 2022;194:556–62.

    Article  CAS  PubMed  Google Scholar 

  40. Qu L, Zhu Y, Liu Y, Yang H, Zhu C, Ma P. Protective effects of ginsenoside Rk3 against chronic alcohol-induced liver injury in mice through inhibition of inflammation, oxidative stress, and apoptosis. Food Chem Toxicol. 2019;126:277–84.

    Article  CAS  PubMed  Google Scholar 

  41. Liu X, Mi X, Wang Z, Zhang M, Hou J, Jiang S, et al. Ginsenoside Rg3 promotes regression from hepatic fibrosis through reducing inflammation-mediated autophagy signaling pathway. Cell Death Dis. 2020;11(6):454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. • He Z, Chen S, Pan T, Li A, Wang K, Lin Z, et al. Ginsenoside Rg2 ameliorating CDAHFD-induced hepatic fibrosis by Regulating AKT/mTOR-mediated autophagy. J Agric Food Chem. 2022;70(6):1911–22. This study evaluates the potential anti fibrotic effects of G-Rg2, including possible mechanisms. For the first time, it has been revealed whether G-Rg2 can inhibit HSC autophagy without affecting or promoting liver cell autophagy, thereby more safely and effectively inhibiting liver fibrosis.

  43. Wei X, Chen Y, Huang W. Ginsenoside Rg1 ameliorates liver fibrosis via suppressing epithelial to mesenchymal transition and reactive oxygen species production in vitro and in vivo. BioFactors. 2018;44(4):327–35.

    Article  CAS  Google Scholar 

  44. Cai Y, Li H, Liu M, Pei Y, Zheng J, Zhou J, et al. Disruption of adenosine 2A receptor exacerbates NAFLD through increasing inflammatory responses and SREBP1c activity. Hepatology. 2018;68(1):48–61.

    Article  CAS  PubMed  Google Scholar 

  45. Wei X, Chen Y, Huang W. Ginsenoside Rg1 ameliorates liver fibrosis via suppressing epithelial to mesenchymal transition and reactive oxygen species production in vitro and in vivo. Biofactors. 2018;44(4).

  46. Li Y, Zhang D, Li L, Han Y, Dong X, Yang L, et al. Ginsenoside Rg1 ameliorates aging‑induced liver fibrosis by inhibiting the NOX4/NLRP3 inflammasome in SAMP8 mice. Mol Med Rep. 2021;24.

  47. Zhang R, Li X, Gao Y, Tao Q, Lang Z, Zhan Y, et al. Ginsenoside Rg1 epigenetically modulates Smad7 expression in liver fibrosis via MicroRNA-152. J Ginseng Res. 2023;47:534–42.

    Article  PubMed  Google Scholar 

  48. • Zaghloul RA, Zaghloul AM, El-Kashef DH. Hepatoprotective effect of Baicalin against thioacetamide-induced cirrhosis in rats: targeting NOX4/NF-κB/NLRP3 inflammasome signaling pathways. Life Sci. 2022;295:120410. This study conducted an in-depth study on the liver protective effect of the edible ingredient Baicalin, which is administered through TGF-β 1/NOX4/NF-κ. The B/NLRP3 pathway exerts anti-fibrotic effects while also exhibiting anti-inflammatory and antioxidant effects. Baicalin targets NOX4/NF-κ. The B/NLRP3 inflammasome pathway has been evaluated as a possible mechanism of its potential anti-fibrotic effect.

  49. Xiao Y, Ye J, Zhou Y, Huang J, Liu X, Huang B, et al. Baicalin inhibits pressure overload-induced cardiac fibrosis through regulating AMPK/TGF-β/Smads signaling pathway. Arch Biochem Biophys. 2018;640:37–46.

    Article  CAS  PubMed  Google Scholar 

  50. Liu J, Yuan Y, Gong X, Zhang L, Zhou Q, Wu S, et al. Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice. Arch Biochem Biophys. 2020;80: 106208.

    CAS  Google Scholar 

  51. Zhang J, Zhang H, Deng X, Zhang N, Liu B, Xin S, et al. Baicalin attenuates non-alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, inflammation and fibrosis in mice. Life Sci. 2017;192:46–54.

    Article  PubMed  ADS  Google Scholar 

  52. Shen K, Feng X, Pan H, Zhang F, Xie H, Zheng S. Baicalin ameliorates experimental liver cholestasis in mice by modulation of oxidative stress, inflammation, and NRF2 transcription factor. Oxid Med Cell Longev. 2017;6169128:1–11.

    Google Scholar 

  53. El-Hameed NM, El-Aleem SA, Khattab MA, Ali AH, Mohammed HH. Curcumin activation of nuclear factor E2-related factor 2 gene (Nrf2): prophylactic and therapeutic effect in nonalcoholic steatohepatitis (NASH). Life Sci. 2021;285: 119983.

    Article  Google Scholar 

  54. Che Y, Shi X, Zhong X, Zhang Y, Si R, Li Y, et al. Resveratrol prevents liver damage in MCD-induced steatohepatitis mice by promoting SIGIRR gene transcription. J Nutr Biochem. 2020;82: 108400.

    Article  CAS  PubMed  Google Scholar 

  55. Li L, Hai J, Li Z, Zhang Y, Peng H, Li K, et al. Resveratrol modulates autophagy and NF-κB activity in a murine model for treating non-alcoholic fatty liver disease. Food Chem Toxicol. 2014;63:166–73.

    Article  CAS  PubMed  Google Scholar 

  56. Abd-Elgawad H, Abu-Elsaad N, El-Karef A, Ibrahim T. Piceatannol increases the expression of hepatocyte growth factor and IL-10 thereby protecting hepatocytes in thioacetamide-induced liver fibrosis. Can J Physiol Pharmacol. 2016;94(7):779–87.

    Article  CAS  PubMed  Google Scholar 

  57. Liang F, Xu X, Tu Y. Resveratrol inhibited hepatocyte apoptosis and alleviated liver fibrosis through miR-190a-5p /HGF axis. Bioorg Med Chem. 2022;57: 116593.

    Article  CAS  PubMed  Google Scholar 

  58. Albrahim T, Alonazi MA. Lycopene corrects metabolic syndrome and liver injury induced by high fat diet in obese rats through antioxidant, anti-inflammatory, antifibrotic pathways. Biomed Pharmacother. 2021;141: 111831.

    Article  CAS  PubMed  Google Scholar 

  59. Saeed NM, Mansour AM, Allam S. Lycopene induces insulin signaling and alleviates fibrosis in experimental model of non-alcoholic fatty liver disease in rats. Pharma Nutrition. 2020;14(1): 100225.

    Article  Google Scholar 

  60. Zeng Z, He W, Jia Z, Hao S. Lycopene improves insulin sensitivity through inhibition of STAT3/Srebp-1c-mediated lipid accumulation and inflammation in mice fed a high-fat diet. Exp Clin Endocrinol Diabetes. 2017;125:610–7.

    Article  CAS  PubMed  Google Scholar 

  61. Liu P, Wu P, Yang B, Wang T, Li J, Song X, et al. Kaempferol prevents the progression from simple steatosis to non-alcoholic steatohepatitis by inhibiting the NF-κB pathway in oleic acid-induced HepG2 cells and high-fat diet-induced rats. J Funct Foods. 2021;85: 104655.

    Article  CAS  Google Scholar 

  62. Lu Y, Shao M, Xiang H, Zheng P, Wu T, Ji G. Integrative transcriptomics and metabolomics explore the mechanism of kaempferol on improving nonalcoholic steatohepatitis. Food Function. 2020;11:10058–9.

    Article  CAS  PubMed  Google Scholar 

  63. Lemmens KJA, Van De Wier B, Koek GH, Köhler E, Drittij MJ, Van Der Vijgh WJF, et al. Haenen GRMM: the flavonoid monoHER promotes the adaption to oxidative stress during the onset of NAFLD. Biochem Biophys Res Commun. 2015;456:179–82.

    Article  CAS  PubMed  Google Scholar 

  64. Miao Y, Wu Y, Jin Y, Lei M, Nan J, Wu X. Benzoquinone derivatives with antioxidant activity inhibit activated hepatic stellate cells and attenuate liver fibrosis in TAA-induced mice. Chem-Biol Interact. 2020;317: 108945.

    Article  CAS  PubMed  Google Scholar 

  65. Zhong X, Liu H. Baicalin attenuates diet induced nonalcoholic steatohepatitis by inhibiting inflammation and oxidative stress via suppressing JNK signaling pathways. Biomed Pharmacother. 2018;98:111–7.

    Article  CAS  PubMed  Google Scholar 

  66. Wang F, Liu JC, Zhou RJ, Zhao X, Liu M, Ye H, et al. Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARalpha-mediated lipogenic gene expression. Chem Biol Interact. 2017;275:171–7.

    Article  CAS  PubMed  Google Scholar 

  67. Tsai MS, Wang YH, Lai YY, Tsou HK, Liou GG, Ko JL, et al. Kaempferol protects against propacetamol-induced acute liver injury through CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress, inflammation and apoptosis in mice. Toxicol Lett. 2018;290:97–109.

    Article  CAS  PubMed  Google Scholar 

  68. Shi M, Cui Y, Liu C, Li C, Liu Z, Kang WY. CYPs-mediated drug-drug interactions on psoralidin, isobavachalcone, neobavaisoflavone and daidzein in rats liver microsomes. Food Chem Toxicol. 2020;136: 111027.

    Article  CAS  PubMed  Google Scholar 

  69. Pingili RB, Pawar AK, Challa SR. Effect of chrysin on the formation of N-acetyl-p-benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes. Chem Biol Interact. 2019;302:123–34.

    Article  CAS  PubMed  Google Scholar 

  70. Liu Y, Xu W, Zhai T, You J, Chen Y. Silibinin ameliorates hepatic lipid accumulation and oxidative stress in mice with non-alcoholic steatohepatitis by regulating CFLAR-JNK pathway. Acta Pharm Sin B. 2019;9:745–57.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Liu L, Sun S, Rui H, Li X. In vitro inhibitory effects of dihydromyricetin on human liver cytochrome P450 enzymes. Pharm Biol. 2017;55:1868–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. He P, Wu Y, Shun J, Liang Y, Cheng M, Wang Y. Baicalin ameliorates liver injury induced by chronic plus binge ethanol feeding by modulating oxidative stress and inflammation via CYP2E1 and NRF2 in mice. Oxid Med Cell Longev. 2017;2017:4820414.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Caro AA, Davis A, Fobare S, Horan N, Ryan C, Schwab C. Antioxidant and pro-oxidant mechanisms of (+) catechin in microsomal CYP2E1-dependent oxidative stress. Toxicol In Vitro. 2019;54:1–9.

    Article  CAS  PubMed  Google Scholar 

  74. Gao Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta Gen Subj. 1999;1472:643–50.

    Article  CAS  Google Scholar 

  75. Liao X, Wen Q, Zhang L, Lu L, Zhang L, Luo X. Effect of dietary supplementation with flavonoid from Scutellaria baicalensis Georgi on growth performance, meat quality and antioxidative ability of broilers. J Integr Agr. 2018;17:1165–70.

    Article  CAS  Google Scholar 

  76. Yu H, Jiang X, Dong F, Zhang F, Ji X, Xue M, et al. Lipid accumulation-induced hepatocyte senescence regulates the activation of hepatic stellate cells through the Nrf2-antioxidant response element pathway. Exp Cell Res. 2021;405: 112689.

    Article  CAS  PubMed  Google Scholar 

  77. Zhao H, Eguchi S, Alam A, Ma D. The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury. Am J Physiol Lung Cell Mol Physiol. 2017;312:155–62.

    Article  Google Scholar 

  78. Lu X, Liu M, Dong H, Miao J, Stagos D, Liu M. Dietary prenylated flavonoid xanthohumol alleviates oxidative damage and accelerates diabetic wound healing via Nrf2 activation. Food Chem Toxicol. 2022;160: 112813.

    Article  CAS  PubMed  Google Scholar 

  79. Kabirifar R, Ghoreshi Z, Rezaifar A, Binesh F, Bamdad K, Moradi A. Curcumin, quercetin and atorvastatin protected against the hepatic fibrosis by activating AMP-activated protein kinase. J Funct Foods. 2018;40:341–8.

    Article  CAS  Google Scholar 

  80. Zhu X, Lin X, Zhang P, Liu Y, Ling W, Guo H. Upregulated NLRP3 inflammasome activation is attenuated by anthocyanins in patients with nonalcoholic fatty liver disease: a case-control and an intervention study. Clin Gastroenterol Hepatol. 2022;46: 101843.

    Article  CAS  Google Scholar 

  81. Zhu X, Xiong T, Liu P, Guo X, Xiao L, Zhou F, et al. Quercetin ameliorates HFD-induced NAFLD by promoting hepatic VLDL assembly and lipophagy via the IRE1a/XBP1s pathway. Food Chem Toxicol. 2018;114:52–60.

    Article  CAS  PubMed  Google Scholar 

  82. Ge C, Yu R, Xu M, Li P, Fan C, Li J, et al. Betaine prevented fructose-induced NAFLD by regulating LXRα/PPARα pathway and alleviating ER stress in rats. Eur J Pharmacol. 2016;770:154–64.

    Article  CAS  PubMed  Google Scholar 

  83. Hernández-Aquino E, Quezada-Ramírez MA, Silva-Olivares A, Ramos-Tovar E, Flores-Beltrán RE, Segovia J, et al. Curcumin downregulates Smad pathways and reduces hepatic stellate cells activation in experimental fibrosis. Ann Hepatol. 2020;19(5):497–506.

    Article  PubMed  Google Scholar 

  84. Yu B, Qin S, Hu B, Qin Q, Jiang H, Luo W. Resveratrol improves CCL4-induced liver fibrosis in mouse by upregulating endogenous IL-10 to reprogramme macrophages phenotype from M(LPS) to M(IL-4). Biomed Pharmacother. 2019;117: 109110.

    Article  CAS  PubMed  Google Scholar 

  85. Zhou J, Zou Y, Cai Y, Chi F, Huang W, Shi W, et al. A designed cyclic peptide based on trastuzumab used to construct peptide-drug conjugates for its HER2-targeting ability. Bioorg Chem. 2021;117: 105453.

    Article  CAS  PubMed  Google Scholar 

  86. Deng Z, Liu Y, Liu C, Xiang X, Wang J, Cheng Z, et al. Immature myeloid cells induced by a high-fat diet contribute to liver inflammation. Hepatology. 2009;50(2):1412–20.

    Article  CAS  PubMed  Google Scholar 

  87. Peng CH, Lin HT, Chung DJ, Huang CN, Wang CJ. Mulberry leaf extracts prevent obesity-induced NAFLD with regulating adipocytokines, inflammation and oxidative stress. J Food Drug Anal. 2018;26(2):778–87.

    Article  CAS  PubMed  Google Scholar 

  88. Xiao J, Zhu Y, Liu Y, Tipoe GL, Xing F, So KF. Lycium barbarum polysaccharide attenuates alcoholic cellular injury through TXNIP-NLRP3 inflammasome pathway. Int J Biol Macromol. 2014;69:73–8.

    Article  CAS  PubMed  Google Scholar 

  89. Dai L, Aye TC, Liu X, Xi J, Cheung PCF. TAK1, more than just innate immunity. IUBMB Life. 2012;64(10):825–34.

    Article  CAS  PubMed  Google Scholar 

  90. Vazirian M, Nabavi SM, Jafari S, Manayi A. Natural activators of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and their pharmacological activities. Food Chem Toxicol. 2018;122:69–79.

    Article  CAS  PubMed  Google Scholar 

  91. Herrero-Martín G, Høyer-Hansen M, García-García C, Fumarola C, Farkas T, López-Rivas A, et al. TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells. EMBO J. 2009;28(6):1532–632.

    Article  PubMed Central  Google Scholar 

  92. Jiang W, Wang J, Xue W, Xin J, Shi C, Wen J, et al. Caveolin-1 attenuates acetaminophen aggravated lipid accumulation in alcoholic fatty liver by activating mitophagy via the Pink-1/Parkin pathway. Eur J Pharmacol. 2021;908: 174324.

    Article  CAS  PubMed  Google Scholar 

  93. Kocot AM, Wróblewska B. Fermented products and bioactive food compounds as a tool to activate autophagy and promote the maintenance of the intestinal barrier function. Trends Food Sci Technol. 2021;118:905–19.

    Article  CAS  Google Scholar 

  94. Zheng X, Zhang X, Liu Y, Zhu L, Liang X, Jiang H, et al. Arjunolic acid from Cyclocarya paliurus ameliorates nonalcoholic fatty liver disease in mice via activating Sirt1/AMPK, triggering autophagy and improving gut barrier function. J Funct Foods. 2021;86: 104686.

    Article  CAS  Google Scholar 

  95. Yan L, Zhang S, Luo G, Cheng BC, Zhang C, Wang Y, et al. Schisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway. Metabolism. 2022;131: 155200.

    Article  CAS  PubMed  Google Scholar 

  96. Dai C, Ciccotosto GD, Cappai R, Wang Y, Tang S, Hoyer D, et al. Rapamycin confers neuroprotection against colistin-induced oxidative stress, mitochondria dysfunction, and apoptosis through the activation of autophagy and mTOR/Akt/CREB signaling pathways. ACS Chem Neurosci. 2018;9(4):824–37.

    Article  CAS  PubMed  Google Scholar 

  97. Duan R, Huang K, Guan X, Li S, Xia J, Shen M, et al. Tectorigenin ameliorated high-fat diet-induced nonalcoholic fatty liver disease through anti-inflammation and modulating gut microbiota in mice. Food Chem Toxicol. 2022;164: 112948.

    Article  CAS  PubMed  Google Scholar 

  98. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482:179–85.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  99. Huang H, Chen AY, Rojanasakul Y, Ye X, Rankin GO, et al. Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis. J Funct Foods. 2015;15:464–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ajaz S, Mcphail MJ, Gnudi L, Trovato FM, Mujib S, Napoli S, et al. Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD). Mitochondrion. 2021;57:119–30.

    Article  CAS  PubMed  Google Scholar 

  101. Lee J, Park JS, Roh YS. Molecular insights into the role of mitochondria in non-alcoholic fatty liver disease. Arch Pharm Res. 2019;42(11):935–46.

    Article  CAS  PubMed  Google Scholar 

  102. Ren F, Chen Q, Meng C, Chen H, Zhou Y, Zhang H, et al. Serum metabonomics revealed the mechanism of Ganoderma amboinense polysaccharides in preventing non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet. J Funct Foods. 2021;82: 104496.

    Article  CAS  Google Scholar 

  103. Ren T, Zhu L, Shen Y, Mou Q, Lin T, Feng H. Protection of hepatocyte mitochondrial function by blueberry juice and probiotics via SIRT1 regulation in non-alcoholic fatty liver disease. Food Funct. 2019;10(3):1540–51.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was financially supported by the National Natural Science Foundation of China (Grant No. 81703386), the People’s Livelihood Plan Project of the Department of Science and Technology of Liaoning Province (Grant No. 2021JH2/10300074), the scientific research funding project of the Liaoning Provincial Department of Education (Grant No. 2019LJC12), and the Career Development Support Plan for Young (Grant No. ZQN2019001).

Author information

Authors and Affiliations

  1. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Chong Yu, Xiaohe Guo, Xiaohang Cui & Haifeng Wang

  2. School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Guangyue Su

Authors
  1. Chong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaohe Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaohang Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guangyue Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Haifeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, Haifeng Wang, Guangyue Su and Xiaohang Cui; writing-original draft preparation and editin, Haifeng Wang, Chong Yu and Xiaohe Guo; upervision and project administration, Haifeng Wang and Guangyue Su; All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Haifeng Wang.

Ethics declarations

Conflict of Interest

The authors have no competing interests to declare that are relevant to the content of this article.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, C., Guo, X., Cui, X. et al. Functional Food Chemical Ingredient Strategies for Non-alcoholic Fatty Liver Disease (NAFLD) and Hepatic Fibrosis: Chemical Properties, Health Benefits, Action, and Application. Curr Nutr Rep 13, 1–14 (2024). https://doi.org/10.1007/s13668-023-00514-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13668-023-00514-8

Keywords

Search

Navigation