Tubeimoside I Ameliorates Myocardial Ischemia‐Reperfusion Injury through SIRT3‐Dependent Regulation of Oxidative Stress and Apoptosis

Abstract

Myocardial ischemia-reperfusion injury (MIRI) is a phenomenon that reperfusion leads to irreversible damage to the myocardium and increases mortality in acute myocardial infarction (AMI) patients. There is no effective drug to treat MIRI. Tubeimoside I (TBM) is a triterpenoid saponin purified from Chinese traditional medicine tubeimu. In this study, 4 mg/kg TBM was given to mice intraperitoneally at 15 min after ischemia. And TBM treatment improved postischemic cardiac function, decreased infarct size, diminished lactate dehydrogenase release, ameliorated oxidative stress, and reduced apoptotic index. Notably, ischemia-reperfusion induced a significant decrease in cardiac SIRT3 expression and activity, while TBM treatment upregulated SIRT3’s expression and activity. However, the cardioprotective effects of TBM were largely abolished by a SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). This suggests that SIRT3 plays an essential role in TBM’s cardioprotective effects. In vitro, TBM also protected H9c2 cells against simulated ischemia/reperfusion (SIR) injury by attenuating oxidative stress and apoptosis, and siSIRT3 diminished its protective effects. Taken together, our results demonstrate for the first time that TBM protects against MIRI through SIRT3-dependent regulation of oxidative stress and apoptosis. TBM might be a potential drug candidate for MIRI treatment.

Role of the cGAS-STING Pathway in Aging-related Endothelial Dysfunction

“…Proteins expression was detected by western blot as described previously [ 24 , 25 ]. In brief, the aortas or HAECs were lysed with RIPA lysis buffer containing protease and phosphatase inhibitors at 4 ?…”

Tubeimoside I Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating SIRT3

“…Recently, the triterpenoid saponin TBM, derived from tuberimu , a tuber of Bolbostemma paniculatum , has attracted much attention because of its multiple pharmacological effects, including antitumor activities [ 31 ], anti-inflammatory action [ 44 ], the ability to promote angiogenesis [ 45 ], and to improve endothelial function [ 46 ]. In addition, TBM plays critical protective roles in various cardiovascular diseases [ 36 , 46 ]. TBM administration protects against myocardial ischemia-reperfusion injury by decreasing oxidative stress [ 36 ].…”

“…Mice in the DOX group, DOX + TBM group, and DOX + TBM+3-TYP group were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce acute cardiac injury [ 37 ], while the CON group received an equal volume of normal saline. Before DOX injection, mice in the TBM group, DOX + TBM group, and DOX + TBM+3-TYP group were pretreated with TBM (4 mg/kg/2 days) twice [ 36 ], and then sequentially received TBM (4 mg/kg/2 days) twice. Meanwhile, DOX + TBM+3-TYP group mice were pretreated with 3-TYP (50 mg/kg/2 days) twice, and then sequentially received TBM (4 mg/kg/2 days) twice.…”

Modified Linggui Zhugan Decoction protects against ventricular remodeling through ameliorating mitochondrial damage in post-myocardial infarction rats

“…H9c2 cells (CL-0089, Procell, CHN) were cultured in Dulbecco’s modified Eagle’s medium (DMEM, 11995, Solarbio, CHN) containing 10% fetal bovine serum (FBS,16000044, Gibco, USA) and 1% streptomycin-penicillin (P1400, Solarbio, CHN) at 37°C in a 5% CO 2 atmosphere. Oxygen-glucose deprivation (OGD) was performed to emulate the MI model in vitro ( 37 , 38 ). Briefly, cells were incubated with glucose-free and FBS-free DMEM (11966025, Gibco, USA) and low-oxygen incubator (5% CO 2 , 1% O 2 , and 94% N 2 ), at 37°C for 4 h. After that, the culture solution was replaced with standard culture media or treated with MLZD, in normoxic conditions for another 24 h. The cells were divided into seven groups: CON, OGD, 3-TYP (1 μM, IT1960, Solarbio, CHN), OGD+3-TYP, MLZD, OGD+MLZD (0.5 mg/ml), and OGD+MLZD+3-TYP.…”