UPLC-Q-TOF/MS-based study on chemical composition, in vivo metabolites, and tissue distribution of ethanol extract of...

Ganoderma lucidum (G. lucidum), a medicinal fungus, exhibits diverse pharmacological effects against many diseases. Studies have shown that the ethanol extract of G. lucidum (GLEE), which is rich in triterpenoids, possesses significant anti-carcinogenic effects. Early research focused solely on the pharmacokinetics and metabolism of individual triterpenoids in normal rodents. However, no research has examined the distribution of prototype compounds and metabolites of GLEE in multiple tissues, plasma, or tumor tissue. In this study, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), combined with the Global Natural Products Social Molecular Networking (GNPS) platform and UNIFI software, was employed to identify and quantify the chemical composition of GLEE. A total of 105 compounds were identified, including 100 triterpenoids and 5 fatty acids, with 18 high-content monomers quantitatively analyzed. Following six weeks of GLEE administration in tumor-bearing nude mice, 42 prototype compounds and 24 metabolites were identified across plasma, tumors, and eight tissues, including small intestine, stomach, liver, heart, lung, kidney, spleen, and colon. Notably, ganoderic acids A, B, C1, F, and H were the most widely distributed compounds across these tissues. The metabolism of GLEE involves both phase I and phase II reactions. This study is the first to provide a comprehensive profile of GLEE's chemical composition, distribution, and metabolism, revealing the potential active triterpenoids responsible for its anti-cancer effects. Our findings provide a foundation for future studies focused on the pharmacological mechanisms of these compounds, offering new insights into the therapeutic potential of G. lucidum in cancer treatment.