Antioxidant and Stress Resistance Properties of Flavonoids from Chinese Sea Buckthorn Leaves from the Qinghai-Tibet Plateau.

ABSTRACT

The unique ecological environment of the Qinghai-Tibetan Plateau has endowed Chinese sea buckthorn leaves with rich bioactivities. In this study, we investigated the bioactivity and stress resistance mechanisms of flavonoids derived from Chinese sea buckthorn leaves (FCL) native to the Qinghai-Tibet Plateau. Our analysis identified a total of 57 flavonoids, mainly flavonol glycosides, from FCL, of which 6 were novel flavonoids. Isorhamnetin glycosides, quercetin glycosides and kaempferol glycosides were the three most dominant classes of compounds in FCL. In particular, isorhamnetin-3-O-glucoside-7-O-rhamnoside emerged as the most abundant compound. Our results showed that FCL possesses potent antioxidant properties, as evidenced by its ability to effectively scavenge DPPH free radicals and demonstrate ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) levels comparable to Trolox, a well-known antioxidant standard. Furthermore, FCL showed remarkable efficacy in reducing reactive oxygen species (ROS) levels and malondialdehyde (MDA) levels while enhancing the activities of key antioxidant enzymes, namely superoxide dismutase (SOD) and catalase (CAT), in Caenorhabditis elegans, a widely used model organism. Mechanistically, we elucidated that FCL exerts its stress resistance effects by modulating of transcription factors DAF-16 and HSF-1 within the insulin/insulin-like growth factor-1 signaling pathway (IIS). Activation of these transcription factors orchestrates the expression of downstream target genes including sod-3, ctl-1, hsp16.2, and hsp12.6, thus enhancing the organism's ability to cope with stressors. Overall, our study highlights the rich reservoir of flavonoids in Chinese sea buckthorn leaves as promising candidates for natural medicines, due to their robust antioxidant properties and ability to enhance stress resistance.