Icariside II, a Naturally Occurring SIRT3 Agonist, Protects against Myocardial Infarction through the AMPK/PGC-1α/Apoptosis Signaling Pathway

Abstract

Myocardial infarction (MI) refers to the death of cardiomyocytes triggered by a lack of energy due to myocardial ischemia and hypoxia, and silent mating type information regulation 2 homolog 3 (SIRT3) plays an essential role in protecting against myocardial oxidative stress and apoptosis, which are deemed to be the principal causes of MI. Icariside II (ICS II), one of the main active ingredients of Herbal Epimedii, possesses extensive pharmacological activities. However, whether ICS II can protect against MI is still unknown. Therefore, this study was designed to investigate the effect and possible underlying mechanism of ICS II on MI both in vivo and in vitro. The results showed that pretreatment with ICS II not only dramatically mitigated MI-induced myocardial damage in mice but also alleviated H9c2 cardiomyocyte injury elicited by oxygen and glucose deprivation (OGD), which were achieved by suppressing mitochondrial oxidative stress and apoptosis. Furthermore, ICS II elevated the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) expression, thereby activating SIRT3. However, these protective effects of ICS II on MI injury were largely abolished in SIRT3-deficient mice, manifesting that ICS II-mediated cardioprotective effects are, at least partly, due to the presence of SIRT3. Most interestingly, ICS II directly bound with SIRT3, as reflected by molecular docking, which indicated that SIRT3 might be a promising therapeutic target for ICS II-elicited cardioprotection in MI. In conclusion, our findings illustrate that ICS II protects against MI-induced oxidative injury and apoptosis by targeting SIRT3 through regulating the AMPK/PGC-1α pathway.

Icariside II prevents kidney fibrosis development in chronic kidney disease by promoting fatty acid oxidation

“…More importantly, ICA‐II may have better advantages for biomedical applications compared to icariin due to its higher bio‐availability, faster absorption, longer half‐life, and demonstrated promising pharmacological activities in a variety of disease models (Cheng et al, 2015; Tian et al, 2015). For example, Li and colleagues reported that ICA‐II attenuated myocardial infarction by targeting the SIRT3/AMPK/PGC‐1α pathway (Li et al, 2022). Gao et al demonstrated that pretreatment with ICA‐II exerted significant neuroprotection against ischemic stroke by targeting Nrf2 (Gao et al, 2023).…”

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.…”

Metabolic Regularity of Bioactive Compounds in Epimedium in Rats Based on LC-MS Analysis Technology

“…Obviously, the largest component of C max was lauric acid (3.074 µg mLG 1 ), meanwhile, p-hydroxycinnamic acid, salidroside, liquiritigenin, Icariside I and icariside II reached the maximum plasma concentrations between 0.500 and 1.917 hrs, while, osteoporosis and cancer. For example, icariside II can be used to treat erectile dysfunction 15,16 , cardiovascular and cerebrovascular diseases 17 and diabetic nephropathy 18 . The P-hydroxycinnamic acid has bone protective effect, promotes bone formation and inhibits bone absorption in vivo 19 .…”