Zhi-qiang Cao1, Wei Quan2, Shuang-xing Hou3, Chao Guo4, Shan-bo Ma4, Wei Zhang5, Xin Li6. 1. Department of Urinary Urology, General Hospital of Shenyang Military Region, Shenyang 110840, China. 2. Department of Pharmacy, Xi'an Mental Health Center, Institute of Mental Health, Xi'an Medical University, Xi'an 710061, China. 3. Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. 4. Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. 5. Department of Medical Statistics, School of Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China. 6. Department of Urinary Urology, General Hospital of Shenyang Military Region, Shenyang 110840, China. Electronic address: syzylixin@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza, a perennial plant in the genus Salvia and popularly known as "Danshen", is highly valued for its roots in traditional Chinese medicines (TCMs). It has widely used for the treatment of cerebrovascular and cardiovascular diseases in China. Recently, the cerebral protection of magnesium lithospermate B (MLB), a working extract from Salvia miltiorrhiza, has received more attention. Here, we investigated the therapeutic effects of MLB on cerebral ischemia/reperfusion (CI/R) injury using the middle cerebral artery occlusion (MCAO) model in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to CI/R using a thread to occlude the right middle cerebral artery. After 2h of cerebral ischemia, the middle cerebral artery was reperfused for 24 h. Rats were injected with different doses of MLB (15, 30 and 60 mg/kg). Infarct zones, neurological deficit scores, brain water content, glutamate levels and protein expressions were evaluated after 24h of reperfusion. RESULTS: We found that MLB treatment of rats exposed to focal CI/R decreased neurological deficit scores, brain water content, glutamate levels and cerebral infarct zones. We also demonstrated that MLB can inhibit CI/R injury-induced activation of caspase-3, a marker of apoptosis. This protection by MLB against CI/R injury was accompanied by an upregulation of p-Akt in the ischemic hemisphere. Furthermore, the MLB-induced protection was prevented by treatment with a PI3K inhibitor (LY-294002). CONCLUSIONS: The data in the present study suggest a potential protective role of MLB against CI/R injury in rats. The salient finding of the present study is that this protective effect of MLB is likely mediated through an Akt-dependent pathway.
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza, a perennial plant in the genus Salvia and popularly known as "Danshen", is highly valued for its roots in traditional Chinese medicines (TCMs). It has widely used for the treatment of cerebrovascular and cardiovascular diseases in China. Recently, the cerebral protection of magnesium lithospermate B (MLB), a working extract from Salvia miltiorrhiza, has received more attention. Here, we investigated the therapeutic effects of MLB on cerebral ischemia/reperfusion (CI/R) injury using the middle cerebral artery occlusion (MCAO) model in rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to CI/R using a thread to occlude the right middle cerebral artery. After 2h of cerebral ischemia, the middle cerebral artery was reperfused for 24 h. Rats were injected with different doses of MLB (15, 30 and 60 mg/kg). Infarct zones, neurological deficit scores, brain water content, glutamate levels and protein expressions were evaluated after 24h of reperfusion. RESULTS: We found that MLB treatment of rats exposed to focal CI/R decreased neurological deficit scores, brain water content, glutamate levels and cerebral infarct zones. We also demonstrated that MLB can inhibit CI/R injury-induced activation of caspase-3, a marker of apoptosis. This protection by MLB against CI/R injury was accompanied by an upregulation of p-Akt in the ischemic hemisphere. Furthermore, the MLB-induced protection was prevented by treatment with a PI3K inhibitor (LY-294002). CONCLUSIONS: The data in the present study suggest a potential protective role of MLB against CI/R injury in rats. The salient finding of the present study is that this protective effect of MLB is likely mediated through an Akt-dependent pathway.