Comprehensive chemical profiling of two Dendrobium species and identification of anti-hepatoma active constituents from Dendrobium chrysotoxum by Network Pharmacology

AbstractBackgroundD. nobileandD. chrysotoxumwere important species of the genusDendrobiumand has great economic and medicinal value. The material basis of the medicinal effect ofD. nobileandD. chrysotoxumis still unclear, and the biomarkers associated with the anti-cancer are not entirely clear so far. There is no scientific, universal and measurable quality control system, which greatly restricts the development of theDendrobiumindustry. This study focused on the comprehensive chemical profiling of twoDendrobiumspecies and identification of anti-hepatoma active constituents fromDendrobiumchrysotoxum by Network Pharmacology. Results Chemical profiling showed that altogether 65 phytochemicals were identified fromD. nobileandD. chrysotoxum, with major classes as alkaloids, terpenoids, flavonoids, bibenzyls and phenanthrenes. About 18 compounds were identified as the important differential metabolites inD. nobileandD. chrysotoxum. Furtherly, CCK-8 results showed that the extracts of stems and leaves ofD. nobileandD. chrysotoxumcould inhibit the growth of Huh-7 cells, and the anti-hepatoma activity of extracts were dose-dependent. Among the extracts, the extract ofD. chrysotoxumshowed significant anti-hepatoma activity. To find the material basis and mechanisms underlying the anti-hepatoma activity ofD. chrysotoxum.By constructing and analyzing the compound-target-pathway network, five key compounds and nine key targets were obtained. The five key compounds were chrysotobibenzyl, chrysotoxin, moscatilin, gigantol and chrysotoxene. The nine key targets GAPDH, EGFR, ESR1, HRAS, SRC, CCND1, HIF1A, ERBB2 and MTOR could be considered as the core-targets of the hepatoma activity ofD. chrysotoxumto hepatoma. Conclusions In this study, mass spectrometry-based molecular networking and multivariate statistical analysis was conducted to screen 18 differential metabolites inD. nobileandD. chrysotoxum. CCK-8 results showed thatD. nobileandD. chrysotoxumextracts could inhibit the growth of Huh-7 cells. The molecular network revealed chrysotobibenzyl, chrysotoxin, moscatilin, gigantol and chrysotoxene were identified as core components ofD. chrysotoxumon anti-hepatoma. This study compared the chemical composition differences and anti-hepatoma activities between the whole herbs ofD. nobileandD. chrysotoxum, and revealed the anti-hepatoma effects ofD. chrysotoxumand its potential underlying therapeutic mechanisms in a multi-target and multi-pathway manner.