Ginsenoside Rg1 protects mice against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced liver injury by inhibiting CYP1A1 through the aryl hydrocarbon receptor

Abstract

Ethnopharmacological relevancePanax ginseng C. A. Meyer (ginseng) is a widely used traditional Chinese medicine that has played a beneficial role in the treatment of various diseases, including liver diseases. Ginsenoside Rg1 is a saponin isolated and purified from ginseng that exerts protective effects on the liver in some liver injury models. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous dioxin found mostly in food products that causes liver injury and other human diseases. Although significant efforts have been made to reduce the burden of liver disease, there is still a lack of effective treatment methods.Aim of the study: Although ginsenoside Rg1 was reported to inhibit TCDD-mediated cytochrome P450 1A1 (CYP1A1) induction in HepG2 cells, we sought to verify its hepatoprotective effects and elucidate its mechanism in a TCDD-induced liver injury model in mice. Material and methodsThe mouse liver injury model was established by intraperitoneal TCDD injection, followed by treatment with various doses of ginsenoside Rg1 (50, 100, and 200 mg/kg). Clinical indicators of liver injury, such as an increase in serum aspartate aminotransferase and alanine aminotransferase levels, as well as histopathological changes were evaluated. ResultsThe common clinical indicators of liver injury were detected following TCDD injection, including an increase in serum alanine aminotransferase and aspartate aminotransferase levels, increased relative liver weight, and histopathological changes. Following treatment with ginsenoside Rg1, the levels of aspartate aminotransferase and alanine aminotransferase decreased significantly, and the liver histology was improved. In addition, ginsenoside Rg1 competitively inhibited TCDD-induced Cyp1a1 mRNA transcription through the modulation of aryl hydrocarbon receptor (AhR) nuclear translocation. ConclusionGinsenoside Rg1 is a potent partial AhR agonist that has potential as an effective medication for protecting against TCDD-associated liver injury.