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Molecules. 2014 Jul 30;19(8):11196-210. doi: 10.3390/molecules190811196.

Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways.

Author information

1
Animal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. huang-hhc@sina.com.
2
Animal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. wency@163.com.
3
Animal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. xiazhi0707@126.com.
4
Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. momo198420@hotmail.com.
5
Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. wpaasj@126.com.

Abstract

Rhynchophylline (Rhy) is an alkaloid isolated from Uncaria which has long been recommended for the treatment of central nervous diseases. In our study, the neuroprotective effect of Rhy was investigated in a stroke model, namely permanent middle cerebral artery occlusion (pMCAO). Rats were injected intraperitoneally once daily for four consecutive days before surgery and then received one more injection after surgery. The protein and mRNA levels of p-Akt, p-mTOR, apoptosis-related proteins (p-BAD and cleaved caspase-3), TLR2/4/9, NF-κB, MyD88, BDNF and claudin-5 were examined. Following pMCAO, Rhy treatment not only ameliorated neurological deficits, infarct volume and brain edema, but also increased claudin-5 and BDNF expressions (p < 0.05). Moreover, Rhy could activate PI3K/Akt/mTOR signaling while inhibiting TLRs/NF-κB pathway. Wortmannin, a selective PI3K inhibitor, could abolish the neuroprotective effect of Rhy and reverse the increment in p-Akt, p-mTOR and p-BAD levels. In conclusion, we hypothesize that Rhy protected against ischemic damage, probably via regulating the Akt/mTOR pathway.

PMID:
25079660
PMCID:
PMC6270871
DOI:
10.3390/molecules190811196
[Indexed for MEDLINE]
Free PMC Article

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