Systematic Characterization of Active Antitumor Constituents from the Shaggy Bracket Medicinal Mushroom Inonotus hispidus (Agaricomycetes) by UPLC-Q-TOF/MS and Network Pharmacology.

ABSTRACT

Inonotus hispidus is a well-known medicinal fungus and has been used in the treatment of cancer in China, but the material basis and potential mechanisms are still limited. The present study aimed to use in vitro experiments, UPLC-Q-TOF/MS and network pharmacology to predict active compounds and possible mechanisms of cultivated and wild I. hispidus. The cytotoxicity results in vitro showed that the extracts of cultivated and wild fruit bodies exhibited the highest inhibitory effects against MDA-MB-231 cells, and the 50% inhibition concentration, (IC50) values were 59.82 and 92.09 µg/mL, respectively. Of the two extracts, a total of 30 possible chemical components, including 21 polyphenols and nine fatty acids, were identified. Network pharmacology showed that five active polyphenols (osmundacetone, isohispidin, inotilone, hispolon, and inonotusin A) and 11 potential targets (HSP90AA1, AKT1, STAT3, EGFR, ESR1, PIK3CA, HIF1A, ERBB2, TERT, EP300 and HSP90AB1) were found to be closely associated with antitumor activity. Furthermore, 18 antitumor-related pathways were identified using the compound-target-pathway network. The molecular docking revealed that the active polyphenols had a good binding ability to the core targets, and the results were consistent with those of network pharmacology. Based on these findings, we speculate that I. hispidus can exert its antitumor activity through multicomponent, multitarget, and multichannel mechanisms of action.