Cardioprotective Effect of Ulmus wallichiana Planchon in β-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-α, IL-6, MMP9, β1-AR, TGFβ1 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.

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…This effect was due to induction of autophagy via the “AMP-activated protein kinase” (AMPK) and “mammalian target of rapamycin” (mTOR) signaling pathways ( Y. Wang, B. Rijal, et al, 2020 ), suggesting that ACE2 expression in different regions can be regulated by sympathetic activity. Following treatment with the non-selective β adrenoreceptor agonist isoproterenol, both increased (Nadu, Ferreira, Reudelhuber, Bader, & Santos, 2008) and decreased ( Syed et al, 2016 ) cardiac ACE2 expression have been reported in hypertrophy models. Similarly, while, isoproterenol downregulated cardiac ACE2 expression in a myopathy model (Q.…”

Studies to Elucidate the Mechanism of Cardio Protective and Hypotensive Activities of Anogeissus acuminata (Roxb. ex DC.) in Rodents

“…In cardiac hypertrophy due to hypertension, chronic smaller doses of isoproterenol cause severe oxidative stress on cardiac muscles, resulting in increasing levels of plasma renin and angiotensin II and decreasing levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), NO and cGMP, along with physical parameter ratios cumulatively causing myocytes injury [8,[43][44][45]. Crude extract of Anogeissus acuminata decreased physical parameter ratios, lowered the plasma renin and plasma angiotensin II levels and increased nitrite/nitrate (NO) and cGMP plasma concentration levels against the ISO groups, showing the cardioprotective effects against cardiac hypertrophy.…”

“…The plasma Ag II level, plasma nitrate/nitrite, plasma renin and cGMP concentrations were measured by human/mouse/rat Ang II Enzyme Immunoassay Kit (catalog #: A03E5546, Ray Biotech, Inc. Columbus, OH, USA), Nitrate/Nitrite Assay Kit (catalog#: 7680201; Shaigan chemicals, Lahore, Pakistan), renin ELISA kit of the rat (catalog number: E02R0028; Bio life diagnostics, Berlin, Germany) and enzyme immunoassay (EIA) kit (catalog number: 581021; Shaigan chemicals), respectively, as per instructions provided by the products' manufacturer, by using the reported method [8].…”

“…Similarly, at lower but chronic doses of 05mg/kg/day, ISO binds to beta adrenergic receptors and activates them by causing an increase in heart rate and in plasma angiotensin II and plasma renin levels, which consequently leads to chronic hypertension, causing thickening of myocardial cells. left ventricular hypertrophy ultimately leads to myocardial infarction or heart failure and other cardiac mortalities [8]. Similarly, albino rabbits are used to evaluate the contractile or relaxant effect in aorta and paired atria.…”

Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2

“…These are yet to gain drug regulatory approval and range from traditional Chinese medicinal products to novel molecules, herbal extracts, and repurposed compounds. A list of these compounds with their effects on ACE/ACE2 is provided in Table 1 (Castardeli et al, 2018;Chang et al, 2018;Q.-F. Chen et al, 2019;Chen et al, 2018;Guo et al, 2010;Haber et al, 2014;Kadakol et al, 2015;Lee et al, 2015;Li et al, 2018;Liao et al, 2019;Lin et al, 2017;Liu et al, 2018;Lv et al, 2017;de Macedo et al, 2015;Martínez-Aguilar et al, 2016;Prata et al, 2017;Qaradakhi et al, 2020;Shi et al, 2013;Syed et al, 2016;Tain et al, 2016;Tikellis and Thomas, 2012;Wang et al, 2016Wang et al, , 2018Wei et al, 2015;Wu et al, 2014;Ye et al, 2008;Zhang et al, 2013;Zhao et al, 2015).…”