Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway

Tsutsumi, Yasuo M.; Tsutsumi, Rie; Mawatari, Kazuaki; Nakaya, Yutaka; Kinoshita, Michiko; Tanaka, Katsuya; Oshita, Shuzo

doi:10.1016/j.lfs.2011.02.011

Cited by 53 publications

(32 citation statements)

References 37 publications

(33 reference statements)

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“…The activation of eNOS promotes the synthesis of NO, which then protects the ischemic heart by regulating vascular remodeling and angiogenesis (42,43). It has been shown that the activation of the PI3K-Akt-eNOS pathway alleviates cardiac ischemia-reperfusion injury (44,45), while eNOS deficiency causes myocardial apoptosis and HF (46). In our study, we observed that the administration of muscone significantly induced the phosphorylation of Akt and eNOS, indicating that treatment with muscone may exert protective effects on the ischemic myocardium by activating the PI3K-Akt-eNOS pathway.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

Wang

Meng

Chen

et al. 2014

International Journal of Molecular Medicine

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Musk has been traditionally used in East Asia to alleviate the symptoms of angina pectoris. However, it remains unclear as to whether muscone, the main active ingredient of musk, has any beneficial effects on persistent myocardial ischemia in vivo. The aim of the present study was to investigate whether muscone can improve cardiac function and attenuate myocardial remodeling following myocardial infarction (MI) in mice. Mice were subjected to permanent ligation of the left anterior descending coronary artery to induce MI, and then randomly treated with muscone (2 mg/kg/day) or the vehicle (normal saline) for 3 weeks. Sham-operated mice were used as controls and were also administered the vehicle (normal saline). Treatment with muscone significantly improved cardiac function and exercise tolerance, as evidenced by the decrease in the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, as well as an increase in the left ventricular ejection fraction, left ventricular fractional shortening and time to exhaustion during swimming. Pathological and morphological assessments indicated that treatment with muscone alleviated myocardial fibrosis, collagen deposition and improved the heart weight/body weight ratio. Muscone inhibited the inflammatory response by reducing the expression of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nuclear factor (NF)-κB. Treatment with muscone also reduced myocardial apoptosis by enhancing Bcl-2 and suppressing Bax expression. Muscone also induced the phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS). Our results demonstrate that muscone ameliorates cardiac remodeling and dysfunction induced by MI by exerting anti-fibrotic, anti-inflammatory and anti-apoptotic effects in the ischemic myocardium.

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Section: Discussionmentioning

confidence: 99%

Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

Wang

Meng

Chen

et al. 2014

International Journal of Molecular Medicine

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“…In addition, these pathways are also involved in other biological activities of GS such as decreasing ischemic reperfusion injury , killing of tumors (Ming et al, 2011;Wong et al, 2010) and reducing damage from oxidative stress . Similarly, PI3K signaling after GS treatment has been linked to the decrease of ischemic reperfusion injury (Tsutsumi et al, 2011;Wang and Yuan, 2008) as well as to glucose uptake Shang et al, 2008). Activation of 9.…”

Section: Discussionmentioning

confidence: 99%

High molecular weight polysaccharides are key immunomodulators in North American ginseng extracts: Characterization of the ginseng genetic signature in primary human immune cells

Lemmon

Sham

Chau

et al. 2012

Journal of Ethnopharmacology

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“…Membranes were blocked in PBS containing 2.0% nonfat dry milk and incubated with primary antibody overnight (GLP-1R and caveolins-3, Santa Cruz Biotechnology; GAPDH, Santa Cruz Biotechnology and Cell Signaling Technology) and at 4°C. Bound primary antibodies were visualized using secondary antibodies (Santa Cruz Biotechnology) conjugated with horseradish peroxidase from Santa Cruz Biotechnology and ECL reagent from GE Healthcare [24]. All displayed bands migrated at the appropriate size, as determined by comparison to molecular weight standards (Santa Cruz Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3

Tsutsumi

Hamaguchi

et al. 2014

Cardiovasc Diabetol

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BackgroundExendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO).MethodsMyocytes were treated with exendin-4 and then incubated with methyl-β-cyclodextrin (MβCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels.ResultsExendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MβCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MβCD + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P < 0.001; troponin: 36.9 ± 14.2 vs. 101.1 ± 22.3 ng/ml, P < 0.001). However, exendin-4 induced cardiac protection was abolished in Cav-3 KO mice (infarct size: 43.0 ± 6.4%, P < 0.001; troponin: 96.8 ± 26.6 ng/ml, P = 0.001).ConclusionsWe conclude that caveolae and caveolin-3 are critical for exendin-4 induced protection of the heart from ischemia/reperfusion injury.

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Compound K, a metabolite of ginsenosides, induces cardiac protection mediated nitric oxide via Akt/PI3K pathway

Cited by 53 publications

References 37 publications

Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

Beneficial effects of muscone on cardiac remodeling in a mouse model of myocardial infarction

High molecular weight polysaccharides are key immunomodulators in North American ginseng extracts: Characterization of the ginseng genetic signature in primary human immune cells

Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3

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