Hepatoprotective Effects and Mechanisms of Action of Triterpenoids from Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) on alpha-Amanitin-Induced Liver Injury in Mice

Most fatal mushroom poisonings are caused by species of the genus Amanita; the amatoxins arc responsible for acute liver failure and death in humans. Ganoderma lucidum is a well-known traditional medicinal mushroom that has been shown to have obvious hepatoprotective effects. This study evaluated the hepatoprotective effects of triterpenoids from G. lucidum on liver injury induced by a-amanitin (alpha-AMA) in mice and the mechanisms of action of these triterpenoids, including radical scavenging and antiapoptosis activities. Mice were treated with a-AMA, followed by G. lucidum total triterpenoids or individual triterpenoids, and their hepatoprotective effects were compared with those of the reference drug silibinin (SIL). Treatment with SIL, G. lucidum total triteipenoids, and each of the 5 individual triterpenoids significantly reduced serum alanine aminotransaminase and aspartate aminotransaminase concentrations and reduced mortality rates 20 L.10%. Moreover, triterpenoids and SIL significantly enhanced superoxide dismutase and catalase activity and reduced malondialdehyde content in livers. Treatment with ganoderic acid C2 significantly inhibited DNA fragmentation and decreased caspase-3, -8, and -9 activities. The results demonstrated that triterpenoids have hepatoprotective effects on alpha-AMA-induced liver injury and that their hepatoprotective mechanisms may be the result of their antioxidative and radical scavenging activities and their inhibition of apoptosis.