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Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway.

ABSTRACT: Stachydrine, a constituent of Leonurus japonicus Houtt which also called Japanese motherwort has been shown to improve vascular microcirculation and ameliorate endothelial dysfunction. This study investigated the neuroprotective effect of stachydrine. Male Sprague-Dawley (SD) rats were randomly divided into sham, control, and stachydrine groups. The neurological deficit score was evaluated and the infarct size of the brain was measured using 2,3,5-triphenyltetra-zolium (TTC) chloride staining assay, and the pathological changes in the brain tissues were examined by HE staining. Nissl and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed to assess the numbers of Nissl bodies and the levels of apoptosis in the neurons. The activities of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) were also measured. The release of inflammatory factors IL-1? and TNF-? were detected by Enzyme-linked immunosorbent assay (ELISA). Compared with the control group, the stachydrine group showed a significant prevention of neurological deficit, as indicated by the reduced infarct volume in the brain. Moreover, the stachydrine treatment reduced the activities of SOD, the levels of MDA and decreased the amount of IL-1?, and TNF-?, indicating that it could function to decrease the level of inflammation, thus reducing brain damage. The ischemic stroke model of PC12 cells was prepared via oxygen-glucose deprivation (OGD) protocol for 6 h. The expression of P65 and JAK2/STAT3 signaling pathway related proteins was measured by western blot. The treatment group was found to have the survival rate of PC12 cells improved and the release of inflammatory factors reduced when compared with the OGD group. This study demonstrated that stachydrine could improve nerve function by inhibiting the phosphorylation of P65/JAK2 and STAT3.

SUBMITTER: Li L

PROVIDER: S-EPMC7041339 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway.

Li Li L Sun Lili L Qiu Yan Y Zhu Wenjun W Hu Kangyuan K Mao Junqin J

Frontiers in pharmacology 20200218

Stachydrine, a constituent of Leonurus japonicus Houtt which also called Japanese motherwort has been shown to improve vascular microcirculation and ameliorate endothelial dysfunction. This study investigated the neuroprotective effect of stachydrine. Male Sprague-Dawley (SD) rats were randomly divided into sham, control, and stachydrine groups. The neurological deficit score was evaluated and the infarct size of the brain was measured using 2,3,5-triphenyltetra-zolium (TTC) chloride staining as ...[more]

PMID: 32132924

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Project description:Ischemic stroke is one of the most common causes of mortality worldwide and is a primary cause of disability and mortality in adults. There is an unmet need for drugs that can effectively treat ischemic stroke. Hence, the present study explored the neuroprotective effects of andrographolide (Andro) in a mouse model of bilateral common carotid artery occlusion, and systematically evaluated the potential mechanisms underlying its effects. The effects of Andro on mouse brain tissue following cerebral ischemia‑reperfusion injury (CIRI) were evaluated by histopathological (H&E and Nissl) and immunofluorescence [glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN)] staining. A traditional Chinese medicine‑based network pharmacology method was performed to establish and analyze compound‑target‑disease and function‑pathway networks in order to elucidate the possible mechanisms responsible for the protective role of Andrographis paniculata in CIRI. In addition, western blot analysis and RT‑qPCR was performed to evaluate the expression and activation of signaling proteins predicted to be involved in this mechanism. The amelioration of histopathological alterations was observed in mice pre‑treated with Andro. Immunofluorescence staining revealed that Andro decreased the expression of GFAP and increased the expression of NeuN, and significantly decreased the levels of pro‑inflammatory cytokines (IL‑1β, IL‑6 and TNF‑α). Network pharmacology analysis revealed that neuroinflammatory response and apoptosis were associated with the effects of Andrographis paniculata on CIRI. Western blot analysis revealed that the mice pre‑treated with Andro exhibited an upregulated protein expression of tropomyosin receptor kinase B (TrkB), p‑PI3K and p‑Akt, as well as a decrease in the expression of GFAP and an increase in the expression of NeuN. In addition, the data of RT‑qPCR indicated that the mice pre‑treated with Andro exhibited a significantly decreased expression of encoding IL‑1β mRNA, IL‑6 mRNA and TNF‑α mRNA in the brain compared to the untreated mice following CIRI. On the whole, the findings of the present study suggest that pre‑treatment with Andro exerts a protective effect against CIRI, which may be partly related to its potential to reduce neuroinflammatory response and apoptosis in patients with stroke.

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Dataset Information

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway.

Publications

Protective Effect of Stachydrine Against Cerebral Ischemia-Reperfusion Injury by Reducing Inflammation and Apoptosis Through P65 and JAK2/STAT3 Signaling Pathway.

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