Sanweidoukou decoction, a Chinese herbal formula, ameliorates β-amyloid protein-induced neuronal insult via modulating MAPK/NF-κB signaling pathways: Studies in vivo and in vitro

Abstract

Ethnopharmacological relevanceThe traditional Chinese medicine Sanweidoukou decoction (DK-3) was a classical formula for the treatment of nervous system diseases, recorded in the Chinese medical classic Sibu Yidian. Aim of the studyThe present study is aim to investigate the neuroprotective effects of DK-3 on β-amyloid (Aβ) protein -induced AD-like pathologies and underlying molecular mechanisms both in vitro and in vivo studies. Materials and methodsHydrolysates of DK-3 were analyzed by LC-ESI-MS/MS. In vitro, MTT was utilized to examine effects of DK-3 on Aβ25-35-induced cytotoxicity in PC12 cells. In vivo, male Sprague-Dawley rats were administered with Aβ25-35 to induce AD-like pathologies and behavioral evaluations were conducted via Morris water maze (MWM) test. Histopathological changes were observed by Hematoxylin-eosin (HE) straining. Immunohistochemistry (IHC) was used to detect the tau hyperphosphorylation at Thr181 site. The expression levels of tau hyperphosphorylation, inflammation-related cytokines such as COX-2, iNOS, TNF-α, IL-1β, IL-6, the phosphorylated state of various mitogen-activated protein kinase (MAPK) signaling molecules (p38 MAPK, ERK, and JNK) and activation of nuclear factor κB (NF-κB) in vitro and in vivo were assessed via Western blot. ResultsIn vitro, DK-3 dose-dependently increased cell viability of PC12 cells induced by Aβ25-35. In vivo, DK-3 improved learning and memory abilities of Aβ25-35-induced AD-like rats. Moreover, DK-3 reversed hyperphosphorylation of tau and reduced the production of inflammation-related cytokines through significantly inhibited MAPK and NF-κB signaling pathways both in vitro and in vivo studies. ConclusionThe present study suggested that the traditional Chinese medicine DK-3 may play a role in preventing and treating AD by reducing the hyperphosphorylation of tau protein and the expressions of inflammation-related cytokines via modulating the MAPK/NF-κB signaling pathways.