Metabolomics combined with network pharmacology reveals the effects of ripening stages and edible parts on bioactive ingredients of Luohan Guo (Siraitia grosvenorii).

Luohan Guo (Siraitia grosvenorii) is a traditional food homologous fruit in China, which is famous owing to its rich natural antioxidant secondary metabolites. However, the impacts of ripening stages and edible parts on high-resolution metabolic profiles of Luohan Guo are poorly understood till now, greatly limiting its comprehensive utilization. In this study, an LC-QTOF/MS-based non-targeted metabolomics approach was carried out to reveal the dynamic accumulation of metabolites in the peel and pulp of Luohan Guo across seven growth stages, and further revelation their potential pharmacological activities and mechanisms in the treatment of oxidative stress using the network pharmacology strategy. The results demonstrated that the majority of bioactive ingredients showed great accumulation at the immature stages in both peels and pulps, and the levels of flavonoid glycosides and terpenoid saponins gradually declined as ripening progressed. Notably, the comparative analysis between the full-blown peel and pulp indicated that the peel had higher concentrations of flavonoids, phenols, and alkaloids, whereas terpenoids and amino acids were the significantly enriched bioactive ingredients in the pulp. In addition, network pharmacology analysis screened 28 key pharmacological compounds in Luohan Guo, which primarily acted on 65 core targets to alleviate diseases induced by oxidative damage and predominantly accumulated in the peels collected between the 10th and 20th days, endowing immature peel with the best antioxidant properties. These findings offer valuabley theoretical insights for understanding the secondary metabolite accumulation in different ripening stages and edible parts of Luohan Guo and improving its comprehensive utilization rate.