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Cardioprotective Effect of Ulmus wallichiana Planchon in ?-Adrenergic Agonist Induced Cardiac Hypertrophy.

ABSTRACT: Ulmus wallichiana Planchon (Family: Ulmaceae), a traditional medicinal plant, was used in fracture healing in the folk tradition of Uttarakhand, Himalaya, India. The present study investigated the cardioprotective effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in isoprenaline (ISO) induced cardiac hypertrophy in Wistar rats. Cardiac hypertrophy was induced by ISO (5 mg/kg/day, subcutaneously) in rats. Treatment was performed by oral administration of EE and BF of U. wallichiana (500 and 50 mg/kg/day). The blood pressure (BP) and heart rate (HR) were measured by non-invasive blood pressure measurement technique. Plasma renin, Ang II, NO, and cGMP level were estimated using an ELISA kit. Angiotensin converting enzyme activity was estimated. BP and HR were significantly increased in ISO group (130.33 ± 1.67 mmHg vs. 111.78 ± 1.62 mmHg, p < 0.001 and 450.51 ± 4.90 beats/min vs. 347.82 ± 6.91 beats/min, respectively, p < 0.001). The BP and HR were significantly reduced (EE: 117.53 ± 2.27 mmHg vs. 130.33 ± 1.67 mmHg, p < 0.001, BF: 119.74 ± 3.32 mmHg vs. 130.33 ± 1.67 mmHg, p < 0.001); HR: (EE: 390.22 ± 8.24 beats/min vs. 450.51 ± 4.90 beats/min, p < 0.001, BF: 345.38 ± 6.79 beats/min vs. 450.51 ± 4.90 beats/min, p < 0.001) after the treatment of EE and BF of U. wallichiana, respectively. Plasma renin, Ang II, ACE activity was decreased and NO, cGMP level were increased. The EE and BF of U. wallichiana down regulated the expression of ANP, BNP, TNF-?, IL-6, MMP9, ?1-AR, TGF?1 and up regulated NOS3, ACE2 and Mas expression level, respectively. Thus, this study demonstrated that U. wallichiana has cardioprotective effect against ISO induced cardiac hypertrophy.

SUBMITTER: Syed AA

PROVIDER: S-EPMC5174112 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Cardioprotective Effect of Ulmus wallichiana Planchon in β-Adrenergic Agonist Induced Cardiac Hypertrophy.

Syed Anees A AA Lahiri Shibani S Mohan Divya D Valicherla Guru R GR Gupta Anand P AP Kumar Sudhir S Maurya Rakesh R Bora Himanshu K HK Hanif Kashif K Gayen Jiaur R JR

Frontiers in pharmacology 20161221

Ulmus wallichiana Planchon (Family: Ulmaceae), a traditional medicinal plant, was used in fracture healing in the folk tradition of Uttarakhand, Himalaya, India. The present study investigated the cardioprotective effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in isoprenaline (ISO) induced cardiac hypertrophy in Wistar rats. Cardiac hypertrophy was induced by ISO (5 mg/kg/day, subcutaneously) in rats. Treatment was performed by oral administration of ...[more]

PMID: 28066255

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Project description:BACKGROUND:Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induced pathological cardiac hypertrophy. METHODS:Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy. Cardiac hypertrophy was also induced by Ang II (1.3 mg/kg/d for 4 weeks) in male C57BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic (SIRT2-Tg) mice, and their respective littermates (8 to ?12 weeks old). Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice. RESULTS:SIRT2 protein expression levels were downregulated in hypertrophic hearts from mice. Sirt2 knockout markedly exaggerated cardiac hypertrophy and fibrosis and decreased cardiac ejection fraction and fractional shortening in aged (24-month-old) mice and Ang II-infused mice. Conversely, cardiac-specific SIRT2 overexpression protected the hearts against Ang II-induced cardiac hypertrophy and fibrosis and rescued cardiac function. Mechanistically, SIRT2 maintained the activity of AMP-activated protein kinase (AMPK) in aged and Ang II-induced hypertrophic hearts in vivo as well as in cardiomyocytes in vitro. We identified the liver kinase B1 (LKB1), the major upstream kinase of AMPK, as the direct target of SIRT2. SIRT2 bound to LKB1 and deacetylated it at lysine 48, which promoted the phosphorylation of LKB1 and the subsequent activation of LKB1-AMPK signaling. Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function. CONCLUSIONS:SIRT2 promotes AMPK activation by deacetylating the kinase LKB1. Loss of SIRT2 reduces AMPK activation, promotes aging-related and Ang II-induced cardiac hypertrophy, and blunts metformin-mediated cardioprotective effects. These findings indicate that SIRT2 will be a potential target for therapeutic interventions in aging- and stress-induced cardiac hypertrophy.

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Cardioprotective Effect of Ulmus wallichiana Planchon in ?-Adrenergic Agonist Induced Cardiac Hypertrophy.

Publications

Cardioprotective Effect of <i>Ulmus wallichiana</i> Planchon in β-Adrenergic Agonist Induced Cardiac Hypertrophy.

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