Tubeimoside I ameliorates cerebral ischemia/reperfusion injury through activating SIRT3

Main Article Content

Shaoyue Huang
Zhen Hong
Kuo Li

Keywords

cerebral ischemia-reperfusion (CIR), Tubeimoside I, inflammation, apoptosis, SIRT3

Abstract

Cerebral ischemia-reperfusion (CIR) seriously affects human health and life as it is accompanied by inflammation and apoptosis in brain tissues. Tubeimoside I (TBMS-1) can inhibit neuroinflammation and has neuroprotective effects; however, its effects on ischemia-reperfusion (IR) injury of the brain requires clarity. A mouse cerebral artery occlusion/reperfusion model was used to simulate CIR injury. The neurological function and the area of cerebral infarction were assessed by 2,3,5-triphenyltetrazolium chloride staining. Tumor necrosis factor-α, Interleukin (IL)-1β, IL-6, and IL-10 levels were measured by enzyme-linked-immunosorbent serologic assay kits. Protein blot analysis was performed to assess the expression of apoptosis-related factors. In addition, PC12 (pheochromocytoma) cells were treated with oxygen–glucose deprivation/reoxygenation (OGD/R) to establish an in vitro model of CIR injury. The cell viability was measured by cell counting kit-8 assay, and apoptosis levels were detected by flow cytometry. In vivo results indicated that Tubeimoside I reduced cerebral infarct size, decreased inflammatory factor content, inhibited the expression of apoptosis-related factors, including Bax and cleaved-caspase-3 (Asp175), and promoted the expression of survival factor, such as B-cell lymphoma protein 2. In vitro, Tubeimoside I was able to increase cell viability and inhibit apoptosis. Mechanistically, Tubeimoside I was able to enhance both in vivo and in vitro expressions of NAD-dependent deacetylase sirtuin-3 (SIRT3). SIRT3 inhibitor abolished the protective effect of Tubeimoside I on OGD/R-treated cells. Tubeimoside I lessened CIR injury by activating SIRT3. Hence, it could be a potential drug candidate for treating IR injury of the brain.

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