TY - JOUR
T1 - A Chinese medicine preparation induces neuroprotection by regulating paracrine signaling of brain microvascular endothelial cells
AU - Li, Weihong
AU - Li, Pengtao
AU - Liu, Ziwang
AU - Du, Qinghong
AU - Steinmetz, Andre
AU - Wang, Ning
AU - Du, Huan
AU - Hu, Jinghong
N1 - Funding Information:
This work was supported by the Key Project of Chinese Ministry of Education (Grant no. 109023 ), by the National Natural Science Foundation of China (Grant no. 81273885 ).
PY - 2014/1/10
Y1 - 2014/1/10
N2 - Ethnopharmacological relevance Tong Luo Jiu Nao injection (TLJN), a Chinese medicine preparation, was extracted from the Chinese herbs Panax notoginseng and Gardenia jasminoides. Its pharmacological effect on cerebral ischemia was observed in the study. We previously reported that paracrine signaling of brain microvascular endothelial cells (BMECs) had a direct impact on the survival of neurons in mimicked cerebral ischemia in vitro. The current study was designed to investigate whether paracrine signaling of BMECs could be regulated by drug to achieve neuroprotection. Materials and methods First, an in vitro model of cerebral ischemia in BMECs or neurons was established by oxygen-glucose- deprivation (OGD). TLJN was used as a medicine of intervention. Injured neurons were cultured in the conditioned media from normal and injured BMECs treated with TLJN. The changes in neurons, including the expression of N-methyl-D-aspartate receptor 1(NMDAR1), Ca2+ concentration, cytochrome c release, the mitochondrial membrane potential, were determined by the immunofluorescence staining and molecular Probes. The content of Vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) in various BMECs were also examined by Western blotting and Elisa. Results The results showed the activity of injured neurons was significantly increased when they were grown in conditioned media of normal or injured BMECs treated with TLJN, compared with that of normal or injured BMECs. These changes include a decrease of Ca2+ concentration, of NMDAR1 expression, and of cytochrome c release, also an increase of the mitochondrial membrane potential. Moreover, the VEGF expression was up-regulated and the PAF expression was down-regulated by TLJN in BMECs. Conclusion The results suggest that a neuroprotective effect of TLJN could be achieved by regulating paracrine signaling of BMECs, which could in part be explained by a TLJN-induced up-regulation of VEGF and a down-regulation of PAF in BMECs. Therefore, regulating the paracrine of BMECs could be the important target of the drug action on injured-neurons, which may be a novel path for therapeutic intervention in ischemic injury.
AB - Ethnopharmacological relevance Tong Luo Jiu Nao injection (TLJN), a Chinese medicine preparation, was extracted from the Chinese herbs Panax notoginseng and Gardenia jasminoides. Its pharmacological effect on cerebral ischemia was observed in the study. We previously reported that paracrine signaling of brain microvascular endothelial cells (BMECs) had a direct impact on the survival of neurons in mimicked cerebral ischemia in vitro. The current study was designed to investigate whether paracrine signaling of BMECs could be regulated by drug to achieve neuroprotection. Materials and methods First, an in vitro model of cerebral ischemia in BMECs or neurons was established by oxygen-glucose- deprivation (OGD). TLJN was used as a medicine of intervention. Injured neurons were cultured in the conditioned media from normal and injured BMECs treated with TLJN. The changes in neurons, including the expression of N-methyl-D-aspartate receptor 1(NMDAR1), Ca2+ concentration, cytochrome c release, the mitochondrial membrane potential, were determined by the immunofluorescence staining and molecular Probes. The content of Vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) in various BMECs were also examined by Western blotting and Elisa. Results The results showed the activity of injured neurons was significantly increased when they were grown in conditioned media of normal or injured BMECs treated with TLJN, compared with that of normal or injured BMECs. These changes include a decrease of Ca2+ concentration, of NMDAR1 expression, and of cytochrome c release, also an increase of the mitochondrial membrane potential. Moreover, the VEGF expression was up-regulated and the PAF expression was down-regulated by TLJN in BMECs. Conclusion The results suggest that a neuroprotective effect of TLJN could be achieved by regulating paracrine signaling of BMECs, which could in part be explained by a TLJN-induced up-regulation of VEGF and a down-regulation of PAF in BMECs. Therefore, regulating the paracrine of BMECs could be the important target of the drug action on injured-neurons, which may be a novel path for therapeutic intervention in ischemic injury.
KW - Brain microvascular endothelial cells
KW - Mitochondria
KW - Neurons
KW - Paracrine signaling
KW - Tong Luo Jiu Nao Injection
UR - http://www.scopus.com/inward/record.url?scp=84891489720&partnerID=8YFLogxK
U2 - 10.1016/j.jep.2013.11.035
DO - 10.1016/j.jep.2013.11.035
M3 - Article
C2 - 24280029
AN - SCOPUS:84891489720
SN - 0378-8741
VL - 151
SP - 686
EP - 693
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
IS - 1
ER -