The underlying hepatoprotective mechanism of PKC#963 in alcohol or carbon tetrachloride induced liver injury via inhibition of iNOS, COX-2, and p-STAT3 and enhancement of SOD and catalase

Phytother Res. 2023 Feb;37(2):505-514. doi: 10.1002/ptr.7630. Epub 2022 Sep 23.

Abstract

The aim of the present study is to explore the underlying hepatoprotective mechanism of PKC#963, consisting of Pinus koraiensis, Saururus chinensis, and Lycium barbarum in association with acute and chronic liver injury induced by alcohol or carbon tetrachloride (CCl4). Here, PKC#963 significantly suppressed aspartate aminotransferase (AST), alanine aminotransferase (ALT), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2) in CCl4-treated HepG2 cells. Also, PKC#963 significantly suppressed reactive oxygen species (ROS) production in HepG2 cells. Consistently, PKC#963 suppressed the expression of AST, ALT, p-STAT3, iNOS, COX-2, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and α-smooth muscle actin (α-SMA) and increased procaspase 3 in the liver tissues of CCl4 treated rats. In addition, PKC#963 enhanced alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) for alcohol metabolism, superoxide dismutase (SOD), and catalase as antioxidant enzymes and also suppressed AST and ALT in alcohol-treated rats. Furthermore, PKC#963 reduced hepatic steatosis and necrosis in CCl4-treated rats by H&E (Hematoxylin and Eosin) staining. Taken together, these findings highlight evidence that PKC#963 has hepatoprotective potential via inhibition of iNOS, COX-2, and p-STAT3 and enhancement of SOD and catalase.

Keywords: PKC#963; antioxidant; hepatoprotetcive; inflammation.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Carbon Tetrachloride / toxicity
  • Catalase / metabolism
  • Chemical and Drug Induced Liver Injury* / pathology
  • Chemical and Drug Induced Liver Injury, Chronic*
  • Cyclooxygenase 2 / metabolism
  • Ethanol
  • Liver / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • STAT3 Transcription Factor / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Catalase
  • Cyclooxygenase 2
  • Carbon Tetrachloride
  • Nitric Oxide Synthase Type II
  • STAT3 Transcription Factor
  • Ethanol
  • Superoxide Dismutase
  • Alanine Transaminase