Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways
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...
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MDPI AG
2014-07-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/8/11196 |
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| author | Houcai Huang Rongling Zhong Zhi Xia Jie Song Liang Feng |
| author_facet | Houcai Huang Rongling Zhong Zhi Xia Jie Song Liang Feng |
| author_sort | Houcai Huang |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T22:33:00Z |
| publishDate | 2014-07-01 |
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| spelling | doaj.art-96386704efc848e8aa55a958c790e8382022-12-22T00:48:04ZengMDPI AGMolecules1420-30492014-07-01198111961121010.3390/molecules190811196molecules190811196Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling PathwaysHoucai Huang0Rongling Zhong1Zhi Xia2Jie Song3Liang Feng4Animal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, ChinaAnimal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, ChinaAnimal Center, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, ChinaKey Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, ChinaKey Laboratory of Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, ChinaRhynchophylline (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.http://www.mdpi.com/1420-3049/19/8/11196rhynchophyllinepMCAOischemic strokeAkt/mTORBDNF |
| spellingShingle | Houcai Huang Rongling Zhong Zhi Xia Jie Song Liang Feng Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways Molecules rhynchophylline pMCAO ischemic stroke Akt/mTOR BDNF |
| title | Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways |
| title_full | Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways |
| title_fullStr | Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways |
| title_full_unstemmed | Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways |
| title_short | Neuroprotective Effects of Rhynchophylline Against Ischemic Brain Injury via Regulation of the Akt/mTOR and TLRs Signaling Pathways |
| title_sort | neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the akt mtor and tlrs signaling pathways |
| topic | rhynchophylline pMCAO ischemic stroke Akt/mTOR BDNF |
| url | http://www.mdpi.com/1420-3049/19/8/11196 |
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