ABSTRACT
Epimedium has been used for functional foods with many beneficial functions to human health. Wushanicaritin is one of the most important chemicals int Epimedium. This study investigated the neuroprotective effects of wushanicaritin and potential underlying mechanisms. The results demonstrated that wushanicaritin possessed superior intercellular antioxidant activity compared to icaritin. Wushanicaritin, with an EC50 value of 3.87 µM, showed better neuroprotective effect than quercetin, a promising neuroprotection agent. Wushanicaritin significantly reversed lactate dehydrogenase release, reactive oxygen species generation, cell apoptosis, and mRNA expression related to cell apoptosis and oxidative defense, in glutamate-induced PC-12 cells. Wushanicaritin could also maintain the enzymatic antioxidant defense system and mitochondrial function. The suppression of caspase-3 activation and amelioration of mitochondrial membrane potential loss and nucleus morphology changes were involved in the antiapoptotic effect of wushanicaritin. These findings suggested that wushanicaritin possesses excellent intercellular antioxidant and neuroprotective activities, showing potential promise in functional foods.
ABSTRACT
Recent study has evidenced that traditional Chinese medicinal (TCM) plant-derived schaftoside shows promise as a potential drug candidate for COVID-19 treatment. However, the biosynthetic pathway of schaftoside in TCM plants remains unknown. In this study, the genome of the TCM herb Grona styracifolia (Osbeck) H.Ohashi & K.Ohashi (GSO), which is rich in schaftoside, was sequenced, and a high-quality assembly of GSO genome was obtained. Our findings revealed that GSO did not undergo recent whole genome duplication (WGD) but shared an ancestral papilionoid polyploidy event, leading to the gene expansion of chalcone synthase (CHS) and isoflavone 2'-hydroxylase (HIDH). Furthermore, GSO-specific tandem gene duplication resulted in the gene expansion of C-glucosyltransferase (CGT). Integrative analysis of the metabolome and transcriptome identified 13 CGTs and eight HIDHs involved in the biosynthetic pathway of schaftoside. Functional studies indicated that CGTs and HIDHs identified here are bona fide responsible for the biosynthesis of schaftoside in GSO, as confirmed through hairy root transgenic system and in vitro enzyme activity assay. Taken together, the ancestral papilionoid polyploidy event expanding CHSs and HIDHs, along with the GSO-specific tandem duplication of CGT, contributes, partially if not completely, to the robust biosynthesis of schaftoside in GSO. These findings provide insights into the genomic mechanisms underlying the abundant biosynthesis of schaftoside in GSO, highlighting the potential of GSO as a source of bioactive compounds for pharmaceutical development.