Thymus fontanesii attenuates CCl4-induced oxidative stress and inflammation in mild liver fibrosis

Biomed Pharmacother. 2022 Apr:148:112738. doi: 10.1016/j.biopha.2022.112738. Epub 2022 Feb 21.

Abstract

Liver injury is a major public health problem all over the world that raises the demand of developing novel effective and safe remedies. Traditionally, Thyme (Thymus fontanesii) has a therapeutic potential against different organs toxicity due to its antioxidant activity. The present study aimed to evaluate the antioxidant activities in vitro and the possible hepato-protective effects of T. fontanesii aqueous extract (TFAE) against CCl4 induced liver damage (mild fibrosis) in male albino mice and annotate its phytochemical constituents as well. The extract displayed substantial antioxidant activities in vitro and high content of flavonoids and other phenolic compounds. Oral administration of TFAE (especially high dose) significantly suppressed (but with different degrees) the incidence and severity of CCl4 liver toxicity by activating the hepatic antioxidant defense mechanisms, modulating hepatic functions, and decreasing the production of lipid peroxidation, pro-inflammatory mediators, and pro-fibrotic proteins expression including COL1A1, Fn, and TGF-β1. These activities might be attributed to the presence of 58 secondary metabolites (identified by LC-MS), mainly phenolic acids, flavonoids and diterpenoids that were able, according to molecular docking, to bind to the inhibitor's binding site of three protein targets involved in liver inflammation and fibrosis. These results showcase the antioxidant and anti-inflammatory properties of Thyme (Thymus fontanesii), illustrate the protective and beneficial effects of the plant against CCl4-induced hepatic toxicity in mice, and support its consumption, traditional uses and promotes its valorization as nutraceutical product.

Keywords: Anti-inflammatory; Antioxidant; CCl(4); TGF-β; Thyme; Thymus fontanesii.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Carbon Tetrachloride / adverse effects
  • Carbon Tetrachloride / pharmacology*
  • Flavonoids / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Male
  • Mice
  • Molecular Docking Simulation / methods
  • Oxidative Stress / drug effects*
  • Phenols / metabolism
  • Plant Extracts / pharmacology*
  • Thymus Plant / chemistry*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Flavonoids
  • Phenols
  • Plant Extracts
  • Transforming Growth Factor beta1
  • Carbon Tetrachloride