Chemical Characterization and Hepatoprotective Effects of a Standardized Triterpenoid-Enriched Guava Leaf Extract

Nutraceutical/pharmaceutical agents capable of maintaining redox and inflammation homeostasis are considered as candidates for the prevention and/or treatment of liver diseases. Psidium guajava (commonly known as guava) leaf is a commercially available functional food that has been reported to possess hepatoprotective property. However, the hepatoprotective constituents in guava leaf are not known. In the current study, a standardized triterpenoid-enriched extract of guava leaves (TGL) was developed. A new ursolic acid derivative, namely 2α,3β,6β,23,30-pentahydroxyurs-11,13(18)-dien-28,20β-olide (1), and 23 known triterpenoids were isolated and identified from TGL. The hepatoprotective effects of TGL were evaluated through a model using acetaminophen (APAP)-exposed C57BL/6 male mice. Pretreatment of TGL (75 and 150 mg/kg) restored the mice hepatic architecture, improved the serum ALT and AST levels, and reduced the hepatic ROS and MDA contents. Further molecular mechanistic study revealed that TGL modulated Nrf2 and MAPK signaling pathways to alleviate APAP-induced oxidative and inflammatory stress in liver. In addition, the new compound 1 from TGL showed protective effects against APAP-induced cytotoxicity via activation of the Nrf2 pathway in HepG2 cells. Overall, this is the first report on the hepatoprotective effects of a standardized triterpenoid-enriched extract of guava leaves, which supports its potential nutraceutical application in liver disease management.