The Regulatory Roles of Polysaccharides and Ferroptosis-Related Phytochemicals in Liver Diseases

Overview

Journal Nutrients

Date 2022 Jun 10

PMID 35684103

Authors

Yijing Ren

Siyue Li

Zixuan Song

Qiuping Luo

Yingying Zhang

Hao Wang

Affiliations

Soon will be listed here.

Abstract

Liver disease is a global health burden with high morbidity and mortality worldwide. Liver injuries can develop into severe end-stage diseases, such as cirrhosis or hepatocellular carcinoma, without valid treatment. Therefore, identifying novel drugs may promote liver disease treatment. Phytochemicals, including polysaccharides, flavonoids, alkaloids, and terpenes, are abundant in foods and medicinal plants and have various bioactivities, such as antioxidation, immunoregulation, and tumor killing. Recent studies have shown that many natural polysaccharides play protective roles in liver disease models in vitro and in vivo, such as fatty liver disease, alcoholic liver disease, drug-induced liver injury, and liver cancer. The mechanisms of liver disease are complex. Notably, ferroptosis, a new type of cell death driven by iron and lipid peroxidation, is considered to be the key mechanism in many hepatic pathologies. Therefore, polysaccharides and other types of phytochemicals with activities in ferroptosis regulation provide novel therapeutic strategies for ferroptosis-related liver diseases. This review summarizes our current understanding of the mechanisms of ferroptosis and liver injury and compelling preclinical evidence of natural bioactive polysaccharides and phytochemicals in treating liver disease.

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References

Friedmann Angeli J, Schneider M, Proneth B, Tyurina Y, Tyurin V, Hammond V . Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014; 16(12):1180-91. PMC: 4894846. DOI: 10.1038/ncb3064. View

Song M, Li Z, Gu H, Tang R, Zhang R, Zhu Y . Spore Polysaccharide Inhibits the Growth of Hepatocellular Carcinoma Cells by Altering Macrophage Polarity and Induction of Apoptosis. J Immunol Res. 2021; 2021:6696606. PMC: 7954632. DOI: 10.1155/2021/6696606. View

Zhai F, Liang Q, Wu Y, Liu J, Liu J . Red ginseng polysaccharide exhibits anticancer activity through GPX4 downregulation-induced ferroptosis. Pharm Biol. 2022; 60(1):909-914. PMC: 9116236. DOI: 10.1080/13880209.2022.2066139. View

Kisseleva T, Brenner D . Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2020; 18(3):151-166. DOI: 10.1038/s41575-020-00372-7. View

Ho C, Huang J, Sun M, Tzeng I, Hsu Y, Kuo C . Wild Bitter Melon Extract Regulates LPS-Induced Hepatic Stellate Cell Activation, Inflammation, Endoplasmic Reticulum Stress, and Ferroptosis. Evid Based Complement Alternat Med. 2021; 2021:6671129. PMC: 8241502. DOI: 10.1155/2021/6671129. View

Chen L, Zhang L, Wang W, Qiu W, Liu L, Ning A . Polysaccharides isolated from Cordyceps Sinensis contribute to the progression of NASH by modifying the gut microbiota in mice fed a high-fat diet. PLoS One. 2020; 15(6):e0232972. PMC: 7279895. DOI: 10.1371/journal.pone.0232972. View

Dai C, Li H, Wang Y, Tang S, Velkov T, Shen J . Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury. Antioxidants (Basel). 2021; 10(6). PMC: 8235740. DOI: 10.3390/antiox10060976. View

Wang G, Zuo P, Ding K, Zeng Q, Hu T, Wei S . Intervention Study of Dictyophora Polysaccharides on Arsenic-Induced Liver Fibrosis in SD Rats. Biomed Res Int. 2022; 2022:7509620. PMC: 8986371. DOI: 10.1155/2022/7509620. View

Song X, Cui W, Meng F, Xia Q, Li X, Hou M . Glucopyranose from prevent alcoholic liver diseases by regulating Nrf2/HO-1-TLR4/NF-κB signalling pathways and gut microbiota. Food Funct. 2022; 13(5):2441-2455. DOI: 10.1039/d1fo03486c. View

10.

Bonora M, Giorgi C, Pinton P . Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol. 2021; 23(4):266-285. DOI: 10.1038/s41580-021-00433-y. View

11.

Kong Z, Liu R, Cheng Y . Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother. 2018; 109:2043-2053. DOI: 10.1016/j.biopha.2018.11.030. View

12.

Nepali S, Ki H, Lee J, Cha J, Lee Y, Kim D . Triticum aestivum sprout-derived polysaccharide exerts hepatoprotective effects against ethanol-induced liver damage by enhancing the antioxidant system in mice. Int J Mol Med. 2017; 40(4):1243-1252. DOI: 10.3892/ijmm.2017.3095. View

13.

Shen W, Chen C, Guan Y, Song X, Jin Y, Wang J . A pumpkin polysaccharide induces apoptosis by inhibiting the JAK2/STAT3 pathway in human hepatoma HepG2 cells. Int J Biol Macromol. 2017; 104(Pt A):681-686. DOI: 10.1016/j.ijbiomac.2017.06.078. View

14.

Andrade R, Chalasani N, Bjornsson E, Suzuki A, Kullak-Ublick G, Watkins P . Drug-induced liver injury. Nat Rev Dis Primers. 2019; 5(1):58. DOI: 10.1038/s41572-019-0105-0. View

15.

Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G, Buday K . Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis. Cell. 2018; 172(3):409-422.e21. DOI: 10.1016/j.cell.2017.11.048. View

16.

Wang Z, Li M, Liu Y, Qiao Z, Bai T, Yang L . Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein response‑induced upregulation of CHAC1 expression. Oncol Rep. 2021; 46(5). PMC: 8485000. DOI: 10.3892/or.2021.8191. View

17.

Marcellin P, Kutala B . Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018; 38 Suppl 1:2-6. DOI: 10.1111/liv.13682. View

18.

Wang X, Luo J, Chen R, Zha X, Wang H . The effects of daily supplementation of Dendrobium huoshanense polysaccharide on ethanol-induced subacute liver injury in mice by proteomic analysis. Food Funct. 2014; 5(9):2020-35. DOI: 10.1039/c3fo60629e. View

19.

Pohl K, Moodley P, Dhanda A . Alcohol's Impact on the Gut and Liver. Nutrients. 2021; 13(9). PMC: 8472839. DOI: 10.3390/nu13093170. View

20.

Parmar D, Apte M . Angiopoietin inhibitors: A review on targeting tumor angiogenesis. Eur J Pharmacol. 2021; 899:174021. DOI: 10.1016/j.ejphar.2021.174021. View