Polyphenols Synergistic Drugs to Ameliorate Non-alcoholic Fatty Liver Disease Via Signal Pathway and Gut Microbiota: A Review

Overview

Journal J Adv Res

Specialties General Medicine
Science

Date 2024 Mar 12

PMID 38471648

Authors

Hongcai Li

Jingjing Liang

Mengzhen Han

Zhenpeng Gao

Affiliations

Soon will be listed here.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with an increasing incidence worldwide. Single drug therapy may have toxic side effects and disrupt gut microbiota balance. Polyphenols are widely used in disease intervention due to their distinctive nutritional properties and medicinal value, which a potential gut microbiota modulator. However, there is a lack of comprehensive review to explore the efficacy and mechanism of combined therapy with drugs and polyphenols for NAFLD.

Aim Of Review: Based on this, this review firstly discusses the link between NAFLD and gut microbiota, and outlines the effects of polyphenols and drugs on gut microbiota. Secondly, it examined recent advances in the treatment and intervention of NAFLD with drugs and polyphenols and the therapeutic effect of the combination of the two. Finally, we highlight the underlying mechanisms of polyphenol combined drug therapy in NAFLD. This is mainly in terms of signaling pathways (NF-κB, AMPK, Nrf2, JAK/STAT, PPAR, SREBP-1c, PI3K/Akt and TLR) and gut microbiota. Furthermore, some emerging mechanisms such as microRNA potential biomarker therapies may provide therapeutic avenues for NAFLD.

Key Scientific Concepts Of Review: Drawing inspiration from combination drug strategies, the use of active substances in combination with drugs for NAFLD intervention holds transformative and prospective potential, both improve NAFLD and restore gut microbiota balance while reducing the required drug dosage. This review systematically discusses the bidirectional interactions between gut microbiota and NAFLD, and summarizes the potential mechanisms of polyphenol synergistic drugs in the treatment of NAFLD by modulating signaling pathways and gut microbiota. Future researches should develop multi-omics technology to identify patients who benefit from polyphenols combination drugs and devising individualized treatment plans to enhance its therapeutic effect.

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References

Rosenblat M, Volkova N, Aviram M . Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis. 2012; 226(1):110-7. DOI: 10.1016/j.atherosclerosis.2012.10.054. View

Su H, Li Y, Hu D, Xie L, Ke H, Zheng X . Procyanidin B2 ameliorates free fatty acids-induced hepatic steatosis through regulating TFEB-mediated lysosomal pathway and redox state. Free Radic Biol Med. 2018; 126:269-286. DOI: 10.1016/j.freeradbiomed.2018.08.024. View

Rodriguez-Ramiro I, Ramos S, Bravo L, Goya L, Martin M . Procyanidin B2 induces Nrf2 translocation and glutathione S-transferase P1 expression via ERKs and p38-MAPK pathways and protect human colonic cells against oxidative stress. Eur J Nutr. 2011; 51(7):881-92. DOI: 10.1007/s00394-011-0269-1. View

Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A . Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. Cell Metab. 2017; 25(5):1054-1062.e5. PMC: 5502730. DOI: 10.1016/j.cmet.2017.04.001. View

Dakhale G, Chaudhari H, Shrivastava M . Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: a randomized, double-blind study. Adv Pharmacol Sci. 2012; 2011:195271. PMC: 3254006. DOI: 10.1155/2011/195271. View

Kim M, Seong J, Huh J, Bae Y, Lee H, Lee D . Peroxiredoxin 5 ameliorates obesity-induced non-alcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling. Redox Biol. 2019; 28:101315. PMC: 6736789. DOI: 10.1016/j.redox.2019.101315. View

Shi Z, Gao J, Yuan Y, Zhu S, Yao M . Effect of raw Radix Rehmanniae on the pharmacokinetics of pioglitazone in rats. Pak J Pharm Sci. 2014; 27(3):537-9. View

Wang X, Zhang D, Gu T, Ding X, Fan C, Zhu Q . Morin reduces hepatic inflammation-associated lipid accumulation in high fructose-fed rats via inhibiting sphingosine kinase 1/sphingosine 1-phosphate signaling pathway. Biochem Pharmacol. 2013; 86(12):1791-804. DOI: 10.1016/j.bcp.2013.10.005. View

Jia W, Wei M, Rajani C, Zheng X . Targeting the alternative bile acid synthetic pathway for metabolic diseases. Protein Cell. 2020; 12(5):411-425. PMC: 8106556. DOI: 10.1007/s13238-020-00804-9. View

10.

Sahebkar A, Saboni N, Pirro M, Banach M . Curcumin: An effective adjunct in patients with statin-associated muscle symptoms?. J Cachexia Sarcopenia Muscle. 2016; 8(1):19-24. PMC: 5326825. DOI: 10.1002/jcsm.12140. View

11.

Hong Y, Sheng L, Zhong J, Tao X, Zhu W, Ma J . Desulfovibrio vulgaris, a potent acetic acid-producing bacterium, attenuates nonalcoholic fatty liver disease in mice. Gut Microbes. 2021; 13(1):1-20. PMC: 8205104. DOI: 10.1080/19490976.2021.1930874. View

12.

Del Bas J, Ricketts M, Vaque M, Sala E, Quesada H, Ardevol A . Dietary procyanidins enhance transcriptional activity of bile acid-activated FXR in vitro and reduce triglyceridemia in vivo in a FXR-dependent manner. Mol Nutr Food Res. 2009; 53(7):805-14. PMC: 4142053. DOI: 10.1002/mnfr.200800364. View

13.

Mandal S, Godfrey K, McDonald D, Treuren W, Bjornholt J, Midtvedt T . Fat and vitamin intakes during pregnancy have stronger relations with a pro-inflammatory maternal microbiota than does carbohydrate intake. Microbiome. 2016; 4(1):55. PMC: 5070355. DOI: 10.1186/s40168-016-0200-3. View

14.

Pietrofesa R, Woodruff P, Hwang W, Patel P, Chatterjee S, Albelda S . The Synthetic Lignan Secoisolariciresinol Diglucoside Prevents Asbestos-Induced NLRP3 Inflammasome Activation in Murine Macrophages. Oxid Med Cell Longev. 2017; 2017:7395238. PMC: 5615985. DOI: 10.1155/2017/7395238. View

15.

Liu C, Liao J, Li P . Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease. World J Gastroenterol. 2017; 23(11):1964-1973. PMC: 5360637. DOI: 10.3748/wjg.v23.i11.1964. View

16.

Oh T, Kim S, Caussy C, Fu T, Guo J, Bassirian S . A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis. Cell Metab. 2020; 32(5):901. PMC: 7891106. DOI: 10.1016/j.cmet.2020.10.015. View

17.

Lee H, Jenner A, Low C, Lee Y . Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Res Microbiol. 2006; 157(9):876-84. DOI: 10.1016/j.resmic.2006.07.004. View

18.

Qu L, Liu Q, Zhang Q, Tuo X, Fan D, Deng J . Kiwifruit seed oil prevents obesity by regulating inflammation, thermogenesis, and gut microbiota in high-fat diet-induced obese C57BL/6 mice. Food Chem Toxicol. 2019; 125:85-94. DOI: 10.1016/j.fct.2018.12.046. View

19.

Shen J, Sun B, Yu C, Cao Y, Cai C, Yao J . Choline and methionine regulate lipid metabolism via the AMPK signaling pathway in hepatocytes exposed to high concentrations of nonesterified fatty acids. J Cell Biochem. 2019; 121(8-9):3667-3678. DOI: 10.1002/jcb.29494. View

20.

Al-Zoairy R, Pedrini M, Imran Khan M, Engl J, Tschoner A, Ebenbichler C . Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells. Diabetol Metab Syndr. 2017; 9:1. PMC: 5209910. DOI: 10.1186/s13098-016-0201-1. View