Network pharmacology identification of mechanisms of cerebral ischemia injury amelioration by Baicalin and Geniposide.

Abstract

Cerebral ischemia is one of the main causes of human neurological dysfunction. Baicalin (BC) and Geniposide (GP) and their combination (BC/GP) have an ameliorative effect on cerebral ischemia. Here, we use network pharmacology to predict the targets of BC, GP and BC/GP, then explored the protective mechanisms of the drugs on cerebral ischemia injury caused by abnormal activation of microglia cells in vitro. The results indicate that 45 targets related to cerebral ischemic injury were predicted by network pharmacology, and 26 cerebral ischemia related pathways were extracted by the KEGG database. In vitro lipopolysaccharide (LPS) stimulated BV-2 cells to establish a model of inflammatory injury induced by microglia. The effects of BC, GP and BC/GP on the expression of TNF-α, IL-1β and IL-10, TGF-β and TNF-α were verified. Network pharmacology predicts the regulation of the 5-LOX/CysLTs inflammatory pathway. Finally, we found that GP and BC/GP exert anti-inflammatory and neuroprotective effects by regulating the polarization state of microglia and down-regulating 5-LOX/CysLTs, and has certain protective effects on nerve damage following cerebral ischemia.

• Authors: Jie Wu, Bin Wang, Min Li, Yong-Heng Shi, Chuan Wang, Ya-Guo Kang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 859 Pg. 172484 (Sep 15 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 31229537 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• Flavonoids
• Iridoids
• Receptors, Leukotriene
• geniposide
• baicalin
• cysteinyl leukotriene receptor 2
• Arachidonate 5-Lipoxygenase
• leukotriene D4 receptor

Topics

• Animals
• Arachidonate 5-Lipoxygenase (metabolism)
• Brain Ischemia (drug therapy, metabolism, pathology)
• Cell Line
• Cell Polarity (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Interactions
• Flavonoids (pharmacology, therapeutic use)
• Humans
• Iridoids (pharmacology, therapeutic use)
• Mice
• Microglia (drug effects, pathology)
• Molecular Targeted Therapy
• Receptors, Leukotriene (metabolism)