Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling

Hong, Mi-Hyeon; Na, Se-Won; Jang, Youn-Jae; Yoon, Jung-Joo; Lee, Yun‐Jung; Lee, Ho-Sub; Kim, Hye Yoom; Dh, Kang

doi:10.3390/nu13103484

Cited by 13 publications

(12 citation statements)

References 30 publications

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“…Creatine kinase (CK) is mainly used in the diagnosis of myocardial infarction, which is widely in skeletal muscle, cardiac muscle, and brain tissue. Serum atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) activities are used to diagnose and monitor the course and efficacy of heart failure [ 18 ]. CK, ANP, and BNP levels were considerably greater in the DM group than in the CTL group ( P < 0.01); SMY and Met lowered CK, ANP, and BNP levels ( P < 0.05, P < 0.01) ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

The Protective Effect of Sheng Mai Yin on Diabetic Cardiomyopathy via NLRP3/Caspase-1 Pathway

Zhao

Peng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Sheng Mai Yin (SMY) has therapeutic effects on myocardial infarction (MI), heart failure (HF), diabetic cardiomyopathy (DCM), and myocarditis. To study whether SMY can relieve pyroptosis and play a protective role in diabetic cardiomyopathy, a molecular docking technique was used to predict the possible mechanism of SMY against DCM. Then, a DCM rat model was induced by intraperitoneal injection of streptozotocin (STZ), divided into 5 groups: the DM group (model), SMY-L group (2.7 mL/kg SMY), SMY-M group (5.4 mL/kg SMY), SMY-H group (10.8 mL/kg SMY), and Met group (120 mg/kg metformin). Rats in the CTL group (control) and DM group were given normal saline. After 8 weeks, the levels of blood glucose, lipids, and myocardial enzymes were detected according to the kit instructions. Cardiac function was detected by echocardiography. HE and Masson were used to observing the pathological changes, collagen deposition, and collagen volume fraction (CVF). The apoptosis rate of cardiomyocytes was determined by Tunel. The IL-1β level was determined by ELISA and RT-PCR. The expressions of NLRP3, caspase-1, and GSDMD were measured using RT-PCR and Western blotting. The docking results suggested that SMY may act on NLRP3 and its downstream signal pathway. The in vivo results showed that SMY could reduce blood glucose and lipid levels, improve heart function, improve histopathological changes and myocardial enzymes, and alleviate cardiomyocyte apoptosis and myocardial fibrosis. SMY inhibited the mRNA and protein expressions of NLRP3, ASC, Caspase-1, and GSDMD and IL-1β production. SMY can reduce DCM by regulating the NLRP3/caspase-1 signaling pathway, providing a new research direction for the treatment of DCM.

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Section: Resultsmentioning

confidence: 99%

The Protective Effect of Sheng Mai Yin on Diabetic Cardiomyopathy via NLRP3/Caspase-1 Pathway

Zhao

Peng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…CaN is a serine/threonine protein phosphatase. After activation by the upstream Ca 2+ -calmodulin complex, CaN dephosphorylates the p-NFAT protein and then promotes the nuclear localization of NFAT [ 37 ]. After being combined with GATA-4, the NFAT/GATA-4 complex stimulates hypertrophy-related fetal gene expression [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

The Prevention Role of Theaflavin-3,3′-digallate in Angiotensin II Induced Pathological Cardiac Hypertrophy via CaN-NFAT Signal Pathway

et al. 2022

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Theaflavin-3,3′-digallate (TF3) is a representative theaflavin of black tea and is remarkable for the anti-coronary heart disease effect. As an adaptive response to heart failure, pathological cardiac hypertrophy (PCH) has attracted great interest. In this study, the PCH cell model was established with H9c2 cells by angiotensin II, and the prevention effect and mechanisms of TF3 were investigated. The results showed that the cell size and fetal gene mRNA level were significantly reduced as pretreated with TF3 at the concentration range of 1–10 μM, also the balance of the redox system was recovered by TF3 at the concentration of 10 μM. The intracellular Ca2+ level decreased, Calcineurin (CaN) expression was down-regulated and the p-NFATc3 expression was up-regulated. These results indicated that TF3 could inhibit the activation of the CaN-NFAT signal pathway to prevent PCH, and TF3 may be a potentially effective natural compound for PCH and heart failure.

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“…The production of oxidative stress can damage the membrane lipids of cardiomyocytes, destroy the function and integrity of cardiomyocytes, trigger myocardial cell apoptosis and death and ultimately lead to cardiomyocyte loss and heart disease. Some studies have shown that the protective effect of betulinic acid on I/R- or H/R-induced cardiomyocytes might be related to its upregulation of antioxidative ability [ 23 ]. In this study, we observed that BTA07 reduced the level of MDA, significantly increased levels of SOD and GSH-Px and regulated the activation of caspase-3 in the isolated rat heart during the process of I/R injury in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion

Guo

Cao

Liu

et al. 2022

IJMS

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Myocardial ischemia–reperfusion injury (MIRI) leads to cardiac remodeling and heart failure associated with acute myocardial infarction, which is one of the leading causes of death worldwide. Betulinic acid (BA), a widely distributed lupane-type triterpenoid, has been reported to possess antioxidative activity and inhibit apoptosis in MIRI. Due to the low bioavailability and water insolubility of BA, a previous study found a series of BA-derivative compounds by microbial transformation. In this study, we observe whether there are anti-MIRI effects of BTA07, a BA derivative, on cardiac injuries induced by hypoxia/reoxygenation (H/R) in adult rat cardiomyocytes in vitro and in Langendorff-perfused hearts ex vivo, and further explore its mechanism of cardioprotection to find more efficient BA derivatives. The hemodynamic parameters of isolated hearts were monitored and recorded by a Lab Chart system. The markers of oxidative stress and apoptosis in isolated hearts and adult rat cardiomyocytes (ARCMs) were evaluated. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), protein kinase B (Akt) and phospho-Akt (pAkt, Ser473) induced by H/R were detected via Western blot. The Langendorff experiments showed that BTA07 improves hemodynamic parameters, reduces myocardium damage and infarct size, inhibits levels of myocardial tissue enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary outflow and reduces oxidative stress and the activation of caspase-3 in the myocardium. In vitro, BTA07 reduced cell death and caspase-3 activation and inhibited reactive oxygen species (ROS) generation. Furthermore, the protective effects of BTA07 were attenuated by inhibition of the PI3K/Akt signaling pathway with LY294002 in ARCMs. BTA07 protects ARCMs and isolated hearts from hypoxia–reperfusion partly by inhibiting oxidative stress and cardiomyocyte apoptosis.

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Betulinic Acid Improves Cardiac-Renal Dysfunction Caused by Hypertrophy through Calcineurin-NFATc3 Signaling

Cited by 13 publications

References 30 publications

The Protective Effect of Sheng Mai Yin on Diabetic Cardiomyopathy via NLRP3/Caspase-1 Pathway

The Protective Effect of Sheng Mai Yin on Diabetic Cardiomyopathy via NLRP3/Caspase-1 Pathway

The Prevention Role of Theaflavin-3,3′-digallate in Angiotensin II Induced Pathological Cardiac Hypertrophy via CaN-NFAT Signal Pathway

Cardiac Protection of a Novel Lupane-Type Triterpenoid from Injuries Induced by Hypoxia–Reperfusion

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