Crocetin Protected Human Hepatocyte LO2 Cell From TGF-β-Induced Oxygen Stress and Apoptosis but Promoted Proliferation and Autophagy AMPK/m-TOR Pathway

Overview

Journal Front Public Health

Specialty Public Health

Date 2022 Jul 15

PMID 35836988

Authors

Hongxing Guo

Chenyu Ruan

Xiuhong Zhan

Hao Pan

Yumei Luo

Ke Gao

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the protective effects of crocetin against transforming growth factor-β (TGF-β)-induced injury in LO2 cells.

Methods: Human hepatocyte LO2 cells were pre-treated with crocetin (10 μM) for 6, 12, and 24 h, and then induced by TGF-β. Proliferation, oxidative stress, apoptosis, autophagy, and related proteins were assessed.

Results: Crocetin pre-treating promoted proliferation but suppressed apoptosis in TGF-β-induced LO2 cells. Crocetin protected LO2 cells from TGF-β-induced inflammation and oxygen stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) but enhancing superoxide dismutase (SOD) and glutathione (GSH). Autophagy was suppressed in TGF-β but crocetin promoted autophagy in LO2 cells by mediating Adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (m-TOR) signaling pathway upregulating p-AMPK and p-Beclin-1 but downregulating p-mTOR.

Conclusions: Crocetin protected LO2 cells from TGF-β-induced damage by promoting proliferation and autophagy, and suppressing apoptosis and anti-inflammation regulation of AMPK/m-TOR signaling pathway.

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Commentary: Crocetin protected human hepatocyte LO2 cell from TGF-β-induced oxygen stress and apoptosis but promoted proliferation and autophagy AMPK/m-TOR pathway.

Weiskirchen R Front Public Health. 2022; 10:1002484.

PMID: 36452952 PMC: 9701700. DOI: 10.3389/fpubh.2022.1002484.

References

Lee Y, Hu S, Park Y, Lee J . Health Benefits of Carotenoids: A Role of Carotenoids in the Prevention of Non-Alcoholic Fatty Liver Disease. Prev Nutr Food Sci. 2019; 24(2):103-113. PMC: 6615349. DOI: 10.3746/pnf.2019.24.2.103. View

Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J . Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001; 108(8):1167-74. PMC: 209533. DOI: 10.1172/JCI13505. View

Garcia-Blazquez A, Moratalla-Lopez N, Lorenzo C, Salinas M, Alonso G . Effect of L. Stigmas Microwave Dehydration on Picrocrocin, Safranal and Crocetin Esters. Foods. 2021; 10(2). PMC: 7918863. DOI: 10.3390/foods10020404. View

Fabregat I, Moreno-Caceres J, Sanchez A, Dooley S, Dewidar B, Giannelli G . TGF-β signalling and liver disease. FEBS J. 2016; 283(12):2219-32. DOI: 10.1111/febs.13665. View

Zhang S, Sun W, Wu J, Wei W . TGF-β signaling pathway as a pharmacological target in liver diseases. Pharmacol Res. 2014; 85:15-22. DOI: 10.1016/j.phrs.2014.05.005. View

Bhattacharya D, Mukhopadhyay M, Bhattacharyya M, Karmakar P . Is autophagy associated with diabetes mellitus and its complications? A review. EXCLI J. 2018; 17:709-720. PMC: 6123605. DOI: 10.17179/excli2018-1353. View

Guertin D, Sabatini D . Defining the role of mTOR in cancer. Cancer Cell. 2007; 12(1):9-22. DOI: 10.1016/j.ccr.2007.05.008. View

Niska K, Santos-Martinez M, Radomski M, Inkielewicz-Stepniak I . CuO nanoparticles induce apoptosis by impairing the antioxidant defense and detoxification systems in the mouse hippocampal HT22 cell line: protective effect of crocetin. Toxicol In Vitro. 2015; 29(4):663-71. DOI: 10.1016/j.tiv.2015.02.004. View

Zheng S, Qian Z, Tang F, Sheng L . Suppression of vascular cell adhesion molecule-1 expression by crocetin contributes to attenuation of atherosclerosis in hypercholesterolemic rabbits. Biochem Pharmacol. 2005; 70(8):1192-9. DOI: 10.1016/j.bcp.2005.07.034. View

10.

Sreekanth G, Chuncharunee A, Yenchitsomanus P, Limjindaporn T . Crocetin Improves Dengue Virus-Induced Liver Injury. Viruses. 2020; 12(8). PMC: 7472398. DOI: 10.3390/v12080825. View

11.

Tseng T, Chu C, Huang J, Shiow S, Wang C . Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Lett. 1995; 97(1):61-7. DOI: 10.1016/0304-3835(95)03964-x. View

12.

Gao K, Liu F, Chen X, Chen M, Deng Q, Zou X . Crocetin protects against fulminant hepatic failure induced by lipopolysaccharide/D-galactosamine by decreasing apoptosis, inflammation and oxidative stress in a rat model. Exp Ther Med. 2019; 18(5):3775-3782. PMC: 6781807. DOI: 10.3892/etm.2019.8030. View

13.

Giaccio M . Crocetin from saffron: an active component of an ancient spice. Crit Rev Food Sci Nutr. 2004; 44(3):155-72. DOI: 10.1080/10408690490441433. View

14.

Dhar A, Cherian G, Dhar G, Ray G, Sharma R, Banerjee S . Molecular basis of protective effect by crocetin on survival and liver tissue damage following hemorrhagic shock. Mol Cell Biochem. 2005; 278(1-2):139-46. DOI: 10.1007/s11010-005-7155-1. View

15.

Gao K, Liu F, Guo H, Li J, Zhang Y, Mo Z . miR-224 suppresses HBV replication posttranscriptionally through inhibiting SIRT1-mediated autophagy. Int J Clin Exp Pathol. 2020; 11(1):189-198. PMC: 6957968. View

16.

Dhar A, Mehta S, Dhar G, Dhar K, Banerjee S, Veldhuizen P . Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther. 2009; 8(2):315-23. DOI: 10.1158/1535-7163.MCT-08-0762. View

17.

Shen X, Qian Z, Wang Y, Duan J . Crocetin attenuates norepinephrine-induced cytotoxicity in primary cultured rat cardiac myocytes by antioxidant in vitro. J Asian Nat Prod Res. 2009; 11(5):417-25. DOI: 10.1080/10286020902858838. View

18.

Bauer M, Schuppan D . TGFbeta1 in liver fibrosis: time to change paradigms?. FEBS Lett. 2001; 502(1-2):1-3. DOI: 10.1016/s0014-5793(01)02655-2. View

19.

Chen P, Chen Y, Wang Y, Cai S, Deng L, Liu J . Comparative Evaluation of Hepatoprotective Activities of Geniposide, Crocins and Crocetin by CCl4-Induced liver Injury in Mice. Biomol Ther (Seoul). 2016; 24(2):156-62. PMC: 4774496. DOI: 10.4062/biomolther.2015.094. View

20.

Breitkopf K, Godoy P, Ciuclan L, Singer M, Dooley S . TGF-beta/Smad signaling in the injured liver. Z Gastroenterol. 2006; 44(1):57-66. DOI: 10.1055/s-2005-858989. View