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 Aβ-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 Aβ 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 Aβ/Aβ, 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 Aβ (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 Aβ/Aβ, p-Tau, apoptosis, oxidative stress, and autophagy, transformed immune cells, and increased the expression levels of NMDAR2B, p-CamK Ⅱ, and PKG following Aβ challenge. Moreover, MK-801 blocked the effects of isA and SDC extract on apoptosis, ROS levels, and autophagy in Aβ-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 Aβ-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.
Copyright © 2022 Elsevier GmbH. All rights reserved.
About The Expert
Mengnan Zeng
Aozi Feng
Meng Li
Meng Liu
Pengli Guo
Yuhan Zhang
Qinqin Zhang
Beibei Zhang
Bing Cao
Jufang Jia
Ru Wang
Jun Lyu
Xiaoke Zheng
References
PubMed