title: Neuroprotective effect and underlying mechanism of sodium danshensu [3-(3,4-dihydroxyphenyl) lactic acid from Radix and Rhizoma Salviae miltiorrhizae = Danshen] against cerebral ischemia and reperfusion injury in rats.
abstract: Sodium danshensu (SDSS), the sodium salt of danshensu (DSS), has the same pharmacological effects as DSS. In the present study, we aimed to investigate the neuroprotective effect and possible mechanism of SDSS against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were randomly divided into four groups: sham, control, 30 mg/kg and 60 mg/kg SDSS. Cerebral ischemia was induced by 2 h of middle cerebral artery occlusion (MCAO). Neurological functional deficits were evaluated according to the modified neurological severity score (mNSS); cerebral infarct volume and histological damage were measured by TTC or H-E staining. In addition, the number of apoptotic cells and caspase 3/7 activity were assessed by TUNEL or Caspase-Glo assay. And the expression of apoptosis-regulatory proteins and the PI3K/Akt pathway were investigated by western blotting. Our results showed that treatment with SDSS for 5 days after MCAO remarkably improved neurologic deficits and survival rate, reduced infarct volume and the number of dead neurons. SDSS also decreased the number of apoptotic cells, regulated the expression of Bcl-2 and Bax, and increased the ratio of Bcl-2/Bax. Further study revealed that treatment with SDSS also increased the level of p-Akt and p-GSK-3β. Taken together, our results suggest that SDSS has the neuroprotective effect against cerebral I/R injury, and the potential mechanism might to inhibition of apoptosis through activating the PI3K/Akt signal pathway.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: handsomfish@aliyun.com.
authors.forename: Miaomaio
authors.initials: M
authors.lastname: Xi
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: xysn@163.com.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C028972:dan-shen root extract
keywords: Akt; Apoptosis; Cerebral ischemia/reperfusion; GSK-3β; Sodium danshensu