Alcohol–soluble polysaccharides from Dendrobium officinale flowers as an antidepressant by regulating the gut–brain axis

This research aimed to explore the antidepressant components from Dendrobium officinale flowers (DOF) aqueous extract and their mechanism. Multiple depressive models were successfully used to show that alcohol-soluble polysaccharide-enriched fractions separated from DOF aqueous extract exhibited significant antidepressant effects. Subsequently, a novel alcohol-soluble polysaccharide named ASP was isolated, and its molecular mass was 3.10 × 104 Da. ASP was mainly composed of rhamnose, arabinose, fucose, mannose and glucose, and its glycosidic bond forms mainly included T-Manp, 1 → 2-linked Manp, T-Glcp, 1 → 3,6-linked Manp, 1 → 5-linked Araf, 1 → 6-linked Glcp. Microstructural observation of ASP displayed an irregular lamellar structure. Meanwhile, it was found that ASP could exhibit the significant antidepressant effect by modulating gut bacterial and fungal homeostasis and the levels of short-chain fatty acids to attenuate intestinal barrier disruption and excessive inflammatory responses, thus further achieving a protective effect on neuronal apoptosis and the maintenance of the 5-hydroxytryptamine system by activating the BDNF-TrkB-CREB pathway. Current findings outline using DOF as a rich source of a novel leading polysaccharide against depression.