Pengwei Zhuang1, Yanjun Wan2, Shihan Geng3, Ying He4, Bo Feng5, Zhengliang Ye6, Dazheng Zhou6, Dekun Li6, Hongjun Wei7, Hongyan Li7, Yanjun Zhang8, Aichun Ju9. 1. Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China. 2. Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. 3. Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. 4. Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China. 5. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. 6. Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China. 7. Tianjin JF-Pharmaland Technology Development Co., Ltd., Tianjin, China. 8. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address: zyjsunye@163.com. 9. Tianjin Key Laboratory of Safety Evaluation Enterprise of TCM Injections, Tianjin 300410, China; Tianjin Tasliy Pride Pharmaceutical Co., Ltd., Tianjin 300400, China. Electronic address: juach@tasly.com.
Abstract
BACKGROUND: Inflammatory reactions induced by microglia in the brain play crucial roles in ischemia/reperfusion (I/R) cerebral injuries. Microglia activation has been shown to be closely related to TLR4/NF-κB signal pathways. Salvianolic acids for injection (SAFI) have been used in clinical practice to treat ischemic stroke with reported neuroprotective effects; however, the underlying mechanisms are still uncertain. OBJECTIVE AND METHODS: First, we studied the effect of SAFI on inflammatory responses in LPS-stimulated BV-2 microglia. Then, to discover whether the beneficial in vitro effects of SAFI lead to in vivo therapeutic effects, an MCAO (Middle cerebral artery occlusion) rat model was further employed to elucidate the probable mechanism of SAFI in treating ischemic stroke. Rats in the SAFI group were given SAFI (23 or 46mg/kg) before I/R injury. RESULTS: The results showed that SAFI treatment significantly decreased neuroinflammation and the infarction volume compared with the vehicle group. Activation of microglia cells was reduced, and TLR4/NF-κB signals, which were markedly inhibited by SAFI treatment in ischemic hemisphere, were accompanied by reduced expression and release of cytokines IL-1β and IL-6. CONCLUSION: This study provides evidence that SAFI effectively protects the brain after cerebral ischemia, which may be caused by attenuating inflammation in microglia.
BACKGROUND: Inflammatory reactions induced by microglia in the brain play crucial roles in ischemia/reperfusion (I/R) cerebral injuries. Microglia activation has been shown to be closely related to TLR4/NF-κB signal pathways. Salvianolic acids for injection (SAFI) have been used in clinical practice to treat ischemic stroke with reported neuroprotective effects; however, the underlying mechanisms are still uncertain. OBJECTIVE AND METHODS: First, we studied the effect of SAFI on inflammatory responses in LPS-stimulated BV-2 microglia. Then, to discover whether the beneficial in vitro effects of SAFI lead to in vivo therapeutic effects, an MCAO (Middle cerebral artery occlusion) rat model was further employed to elucidate the probable mechanism of SAFI in treating ischemic stroke. Rats in the SAFI group were given SAFI (23 or 46mg/kg) before I/R injury. RESULTS: The results showed that SAFI treatment significantly decreased neuroinflammation and the infarction volume compared with the vehicle group. Activation of microglia cells was reduced, and TLR4/NF-κB signals, which were markedly inhibited by SAFI treatment in ischemic hemisphere, were accompanied by reduced expression and release of cytokines IL-1β and IL-6. CONCLUSION: This study provides evidence that SAFI effectively protects the brain after cerebral ischemia, which may be caused by attenuating inflammation in microglia.
Authors: Ye Ma; Chan Chen; Shu Zhang; Qiao Wang; Hai Chen; Yuanlin Dong; Zheng Zhang; Yan Li; Zhendong Niu; Tao Zhu; Hai Yu; Bin Liu Journal: Oncotarget Date: 2017-05-23