Pectolinarigenin ameliorates acetaminophen-induced acute liver injury via attenuating oxidative stress and inflammatory response in Nrf2 and PPARa dependent manners

  • Phytomedicine. 2023 May:113:154726. doi: 10.1016/j.phymed.2023.154726.
Qian Li  1 ,  Wen Zhang  2 ,  Nuo Cheng  3 ,  Yadi Zhu  1 ,  Hao Li  3 ,  Shuijun Zhang  3 ,  Wenzhi Guo  4 ,  Guangbo Ge  5
Affiliations
  • 1. Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
  • 2. Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China; Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University; Henan Engineering Technology Research Center of Organ Transplantation; Henan Research Centre for Organ Transplantation, No. 1, East Jianshe Road, Zhengzhou 450001, China.
  • 3. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University; Henan Engineering Technology Research Center of Organ Transplantation; Henan Research Centre for Organ Transplantation, No. 1, East Jianshe Road, Zhengzhou 450001, China.
  • 4. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University; Henan Engineering Technology Research Center of Organ Transplantation; Henan Research Centre for Organ Transplantation, No. 1, East Jianshe Road, Zhengzhou 450001, China. Electronic address: [email protected].
  • 5. Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. Electronic address: [email protected].
PMID: 36863308 DOI: 10.1016/j.phymed.2023.154726
Abstract

Background: Cirsii Japonici Herba Carbonisata (Dajitan in Chinese) has been used to treat liver disorders in Asian countries. Pectolinarigenin (PEC), an abundant constituent in Dajitan, has been found to possess a wide range of biological benefits, including hepatoprotective effects. However, the effects of PEC on acetaminophen (APAP)-induced liver injury (AILI) and the underlying mechanisms have not been studied.

Purposes: To explore the role and mechanisms of PEC in protecting against AILI.

Study design and methods: The hepatoprotective benefits of PEC were studied using a mouse model and HepG2 cells. PEC was tested for its effects by injecting it intraperitoneally before APAP administration. To assess liver damage, histological and biochemical tests were performed. The levels of inflammatory factors in the liver were measured using RT-PCR and ELISA. Western blotting was used to measure the expression of a panel of key proteins involved in APAP metabolism, as well as Nrf2 and PPARα. PEC mechanisms on AILI were investigated using HepG2 cells, while the Nrf2 inhibitor (ML385) and PPARα Inhibitor (GW6471) were used to validate the importance of either Nrf2 and PPARα in the hepatoprotective effects of PEC.

Results: PEC treatment decreased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels in the liver. PEC pretreatment increased the activity of superoxide dismutase (SOD) and glutathione (GSH) while decreasing malondialdehyde production (MDA). PEC could also up-regulate two important APAP detoxification Enzymes (UGT1A1 and SULT1A1). Further research revealed that PEC reduced hepatic oxidative damage and inflammation, and up-regulated APAP detoxification Enzymes in hepatocytes by activating the Nrf2 and PPARα signaling pathways.

Conclusions: PEC ameliorates AILI by decreasing hepatic oxidative stress and inflammation while increasing phase Ⅱ detoxification Enzymes related to APAP harmless metabolism through activation of Nrf2 and PPARα signaling. Hence, PEC may serve as a promising therapeutic drug against AILI.

Keywords
Acetaminophen-induced liver injury; Inflammation; Nrf2; Oxidative stress; PPARα; Pectolinarigenin.
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