title: Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways.
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.
authors: Animal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. huang-hhc@sina.com.
authors: Houcai
authors: H
authors: Huang
authors: Animal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. wency@163.com.
authors: Rongling
authors: R
authors: Zhong
authors: Animal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. xiazhi0707@126.com.
authors: Zhi
authors: Z
authors: Xia
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. momo198420@hotmail.com.
authors: Jie
authors: J
authors: Song
authors: Key Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. wpaasj@126.com.
authors: Liang
authors: L
authors: Feng
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D020520:Brain Infarction / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000078183:Oxindoles; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D062507:Claudin-5; D026121:Indole Alkaloids; D016328:NF-kappa B; D018696:Neuroprotective Agents; D000078183:Oxindoles; D051193:Toll-Like Receptors; D051025:bcl-Associated Death Protein; C052714:rhyncophylline; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D053148:Caspase 3