2. Academic Validation
  3. Grape seed-derived procyanidin inhibits glyphosate-induced hepatocyte ferroptosis via enhancing crosstalk between Nrf2 and FGF12

Grape seed-derived procyanidin inhibits glyphosate-induced hepatocyte ferroptosis via enhancing crosstalk between Nrf2 and FGF12

  • Phytomedicine. 2023 Dec 12:123:155278. doi: 10.1016/j.phymed.2023.155278.
Jingbo Liu 1,  Kun Li 2,  Song Li 3,  Guangcheng Yang 4,  Zhenxian Lin 4,  Zengmin Miao 5
Affiliations

Affiliations

  • 1 College of Biological and Brewing Engineering, Taishan University, No. 525 Dongyue Street, Tai'an, Shandong 271000, China. Electronic address: liujb@tsu.edu.cn.
  • 2 Shanghai Pulmonary Hospital, No.507 Zhengmin Road, Yangpu District, Shanghai 200433, China.
  • 3 College of Basic Medicine, Shandong First Medical University, No. 6699 Qingdao Road, Ji'nan 250024, China.
  • 4 College of Biological and Brewing Engineering, Taishan University, No. 525 Dongyue Street, Tai'an, Shandong 271000, China.
  • 5 College of Life Sciences, Shandong First Medical University, No. 619 Changcheng Road, Tai'an 271016, China. Electronic address: zengminmiao@126.com.
PMID: 38103315 DOI: 10.1016/j.phymed.2023.155278
Abstract

Background: Glyphosate (GLY) exposure induces hepatocyte Ferroptosis through overproduction of Reactive Oxygen Species, regarded as an important contributor to liver damage. Grape seed-derived procyanidin (GSDP) has been reported to be an effective antioxidant, but whether and, if any, how GSDP can attenuate GLY-induced liver injury via inhibiting Ferroptosis is unclear.

Purpose: The current study aimed to investigate the hepato-protective effects and possible mechanisms of GSDP.

Methods: GLY-induced liver damage mice model was established to explore the hepatoprotective roles of GSPE in vivo. Subsequently, bioinformatics methodology was used to predict the key pathways and factors related to the action targets of GSPE against hepatocyte Ferroptosis. Finally, we explored the roles of nuclear factor E2 related factor 2 (Nrf2) and Fibroblast Growth Factor 21 (FGF21) in blunting GLY-induced liver damage via suppressing Ferroptosis in vitro.

Results: GSDP exerts hepato-protective effects in vivo and in vitro through reduced oxidative stress and inhibited Ferroptosis, which was related to the activation of Nrf2. Bioinformatics analysis showed an interaction between Nrf2 and FGF21. Furthermore, Nrf2 inhibition reduced FGF21 expression in the mRNA and protein levels. FGF21 knockdown suppressed Nrf2 expression level, but recombinant FGF21 protein increased Nrf2 expression and promoted Nrf2 translocation into nucleus, suggesting a crosstalk between Nrf2 and FGF21. Intriguingly, the decreased levels of Nrf2 and FGF21 compromised the protective roles of GSDP against GLY-induced hepatocyte Ferroptosis.

Conclusion: These findings suggest that GSDP attenuates GLY-caused hepatocyte Ferroptosis via enhancing the interplay between Nrf2 and FGF21. Thus, GSDP may be a promising natural compound to antagonize ferroptosis-related damage.

Keywords

FGF21; Glyphosate; Grape seed-derived procyanidin; Liver ferroptosis; Nrf2.

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