Neuroprotective Effects of Gabapentin Against Cerebral Ischemia Reperfusion-Induced Neuronal Autophagic Injury via Regulation of the PI3K/Akt/mTOR Signaling Pathways.

Gabapentin (GBP), an analgesic, adjunct antiepileptic, and migraine prophylactic drug, reduces neuronal injury induced by cerebral ischemia reperfusion (IR). However, the underlying biological molecular mechanism of GBP neuroprotection is not clear. In this study, we confirmed that dose-dependent (75 and 150 mg/kg) GBP treatment could significantly reduce IR-induced neuronal death. IR-induced neuronal death was inhibited by pretreatment with 150 mg/kg GBP in a middle cerebral artery occlusion rat model. In addition, 150 mg/kg GBP treatment remarkably promoted the levels of antioxidants and reduced the autophagy of neurons in the infarct penumbra. Moreover, the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway was activated by pretreatment with 150 mg/kg GBP, as detected by Western blot analyses. In vitro, pretreatment of PC12 cells with 450 µM GBP significantly reduced cell death induced by oxygen-glucose deprivation, increased antioxidant function, and reduced the levels of autophagy and reactive oxygen species via activation of the PI3K/Akt/mTOR pathway. This neuroprotection by GBP was inhibited significantly by 10 µM LY294002. In summary, dose-dependent pretreatment with GBP protected against cerebral IR injury via activation of the PI3K/Akt/mTOR pathway, which provided a neuroprotective function to inhibit oxidative stress-related neuronal autophagy.

[Effects of Scutellaria baicalensis stem-leaf total flavonoid on proliferation of vassel smooth muscle cells stimulated by high triglyceride blood serum].

OBJECTIVE: To determine the effects and related mechanism of Scutellaria baicalensis stem-leaf total flavonoid (SSTF) on vascular smooth muscle cells (VSMCs) proliferation induced by high triglyceride blood serum (HTG). METHOD: VSMCs isolated from rat aorta were cultured in vitro and proliferation was stimulated by HTG, SSTF was added to influence the proliferation of VSMCs. The proliferation and cell cycle of VSMCs were determined by MTT assay and flow cytometry, respectively. CO released into the culture media was quantitated by measuring carbon monoxide hemoglobin (COHb). The protein expressions of HO-1 and extracellular signal-regulated kinase (ERK/p-ERK) were detected by Western blot analysis. RESULT: 500 mg x L(-1) SSTF could obviously suppress the cell multiplication by HTG's induction, remarkably increase the production of COHb in VSMCs, obviously suppresse the mitotic cycle progress of VSMCs (P < 0.05, P < 0.01), in the time and dosage dependence. Furthermore, 500 mg x L(-1) SSTF remarkably declined the ERK/p-ERK protein expression (P < 0.01), but did not have the influence on the HO-1 protein's expression. CONCLUSION: SSTF inhibited the proliferation of VSMCs directly by blocking cell cycle progression, and the ERK signal transduction way possibly participated in the cytoprotection of SSTF.

[Study on effect and mechanism of scutellaria baicalensis stem-leaf total flavonoid in regulating lipid metabolism].

OBJECTIVE: To investigate the effect and mechanism of Scutellaria Baicalensis Stem-leaf Total Flavonoid (SSTF) on lipid metabolism in hyperlipidemic rat. METHOD: On the basis of establishing hyperlipidemia rat model, blood lipids, lipid metabolic enzyme, antioxidative capacity were investigated after 30 days feeding of fatty emulsion. RESULT: SSTF significantly reduced the serum TC, TG, LDL-C, ApoB concentration and increased HDL-C and ApoAI levels, improved the activity of lecithin cholesterol acyltransferase (LCAT). SSTF was shown to decreased MDA content in both serum and liver, increased serum SOD activity. CONCLUSION: SSTF could remarkably modulate the lipid metabolic disorder in hyperlipidemic rats, and has a certain regulating function on lipoprotein, inferring that it could reduce the occuring of atherosclerosis. The mechanism of regulating lipid metabolism might be related with the increasing activity of LCAT and antioxidative capacity.