Characterization, antioxidant effects of Lycium ruthenicum Murr. Polysaccharides and protective effects against Oxaliplatin-induced peripheral neurotoxicity through inhibition of the RAS - RAF - MEK - ERK signaling pathway.

Oxaliplatin is a frequently used chemotherapeutic agent; however, oxaliplatin-induced peripheral neuropathy (OIPN) is a prevalent adverse effect for which no effective treatment is currently available. Lycium ruthenicum Murr. (LR), a traditional Chinese medicinal herb that is also consumed as food, is rich in polysaccharides. However, the influence of alcohol precipitation concentration on the structure and bioactivities of polysaccharides derived from LR (LRPs) and the effect of LRPs on OIPN remain unclear. Herein, three novel LRPs (LRP-20, LRP-50, and LRP-80) were isolated using 20 %, 50 % and 80 % ethanol, respectively, from crude LRPs extracted with hot water. LRP-20 (5846 Da), LRP-50 (7327 Da), and LRP-80 (9980 Da) differed in monosaccharide composition and content. Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction analysis, and thermal stability assessment revealed differences in the structural properties of the three LRPs. In vitro experiments revealed that LRP-20 exhibited the optimal antioxidant activity, which is relevant to the primary pathogenic mechanisms underlying OIPN. In a rat model of OIPN, LRP-20 alleviated OIPN by increasing antioxidant capacity and attenuating inflammatory responses potentially involved the RAS-RAF-MEK-ERK signaling pathway. Overall, this study indicates that ethanol fractional precipitation can initially separate polysaccharides based on structure, which is strongly associated with biological activities, and offers a strategy for further development of LRPs.