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.
Highlights
Stroke is the third leading cause of death in the USA
Phosphoinositide 3-kinases (PI3Ks) and their downstream target Akt belong to a conserved family of signal transduction enzymes, which plays an important part in regulating inflammatory responses and apoptosis [5]
We examined the effect of Rhy at two doses, 10 mg/kg and 30 mg/kg, on ischemic brain damage after permanent middle cerebral artery occlusion (pMCAO) surgery
Summary
Stroke is the third leading cause of death in the USA. About 795,000 Americans suffer from stroke annually [1]. Phosphoinositide 3-kinases (PI3Ks) and their downstream target Akt belong to a conserved family of signal transduction enzymes, which plays an important part in regulating inflammatory responses and apoptosis [5]. Toll-like receptors (TLRs) play an crucial role in cerebral ischemia/reperfusion injury via mediating the inflammatory responses [7]. PI3K/Akt signaling was involved in the protection against cerebral injury by modulating TLR2 [10]. Via regulation of the TLR and neurotrophin signaling pathways, Rhy exhibited anti-convulsive effects in rats with acute seizures. We first investigated whether Rhy could attenuate ischemic brain damage and explored the role of PI3K/Akt and TLRs/nuclear factor-κB (NF-κB) signaling pathways underlying.
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