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.

ETHNOPHARMACOLOGICAL RELEVANCE

The 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 STUDY

The 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 METHODS

Hydrolysates of DK-3 were analyzed by LC-ESI-MS/MS. In vitro, MTT was utilized to examine effects of DK-3 on Aβ-induced cytotoxicity in PC12 cells. In vivo, male Sprague-Dawley rats were administered with Aβ 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.

RESULTS

In vitro, DK-3 dose-dependently increased cell viability of PC12 cells induced by Aβ. In vivo, DK-3 improved learning and memory abilities of Aβ-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.

CONCLUSION

The 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.