Corallodiscus flabellata B. L. Burtt extract and isonuomioside A ameliorate Aβ25−35-induced brain injury by inhibiting apoptosis, oxidative stress, and autophagy via the NMDAR2B/CamK Ⅱ/PKG pathway

Corallodiscus flabellata B. L. Burtt, a traditional Chinese folk medicine used for amnesia, can significantly improve brain injury; however, its active components and underlying mechanism of action remain unclear.To examine the effects and underlying mechanism of action of Corallodiscus flabellata B. L. Burtt (SDC) extract and isolated isonuomioside A (isA) on Aβ25-35-induced brain injury.SDC extract (155 mg/kg, i.g.) or IsA (20 mg/kg, i.g.) was administered over a period of 4 weeks, following which brain injury was induced by Aβ25-35 infusion (200 µM, 3 µl/20 g, i.c.v.). Network pharmacology research gathered existing data on the effects of SDC on Alzheimer's disease. Learning and memory ability, neuronal damage, and the levels of Aβ1-42/Aβ1-40, p-Tau, apoptosis, oxidative stress, autophagy, immune cells, NMDAR2B, p-CamK Ⅱ, and PKG were examined. Furthermore, the antagonistic effect of MK-801 (NMDA receptor blocker, 10 µM) in the presence of isA (10 µM) or SDC extract (20 µg/ml) was investigated in Aβ25-35 (20 µM, 24 h)-induced PC-12 and N9 cells to evaluate whether the observed effects elicited by isA and SDC extract were mediated via the NMDAR2B/CamK Ⅱ/PKG pathway.IsA and SDC extract improved learning and memory ability, reduced neuronal damage, downregulated Aβ1-42/Aβ1-40, p-Tau, apoptosis, oxidative stress, and autophagy, transformed immune cells, and increased the expression levels of NMDAR2B, p-CamK Ⅱ, and PKG following Aβ25-35 challenge. Moreover, MK-801 blocked the effects of isA and SDC extract on apoptosis, ROS levels, and autophagy in Aβ25-35-induced N9 and PC-12 cells, indicating that isA and SDC extract likely exert neuroprotective effects via the NMDAR2B/CamK Ⅱ/PKG pathway.IsA and SDC extract ameliorate Aβ25-35-induced brain injury by inhibiting apoptosis, oxidative stress, and autophagy, which likely occurs via the NMDAR2B/CamK Ⅱ/PKG pathway. These findings may help to elucidate new therapeutic targets and facilitate the development of drugs for the clinical treatment of AD.