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. 2016 Dec 21:7:510.
doi: 10.3389/fphar.2016.00510. eCollection 2016.

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

Affiliations

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

Anees A Syed et al. Front Pharmacol. .

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.

Keywords: Ulmus wallichiana; blood pressure; cardiac hypertrophy; cardiovascular disease; ethnopharmacology; heart rate; isoprenaline.

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Figures

FIGURE 1
FIGURE 1
Effect of Ulmus wallichiana on (A) Heart weight to body weight ratio, (B) Heart weight to tail length ratio, and (C) Heart to tibia length ratio in ISO induced cardiac hypertrophy in wistar rats. Data were analyzed by using one-way ANOVA followed by Newman–Keuls Multiple comparison test. Data are shown as Mean ± SEM; α, control vs. ISO; β, ISO vs. EE; γ, ISO vs. BF; P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.
FIGURE 2
FIGURE 2
Effect of U. wallichiana on BP (A) SBP, (B) DBP, (C) MAP, and (D) HR by NIBP measurement technique in ISO induced cardiac hypertrophy in wistar rats. Data were analyzed by using one-way ANOVA followed by Newman–Keuls Multiple comparison test. Data are shown as Mean ± SEM; α, control vs. ISO; β, ISO vs. EE; γ, ISO vs. BF; ∗∗P < 0.01, ∗∗∗P < 0.001.
FIGURE 3
FIGURE 3
Effect of U. wallichiana on (A) renin concentration, (B) angiotensin converting enzyme (ACE) activity, (C) NO concentration, (D) Ang II concentration, (E) inhibition of human recombinant renin by EE and (F) inhibition of human recombinant renin by BF in ISO induced cardiac hypertrophy in wistar rats. Data were analyzed by using one-way ANOVA followed by Newman–Keuls Multiple comparison test. Data are shown as Mean ± SEM; α, control vs. ISO; β, ISO vs. EE; γ, ISO vs. BF; P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.
FIGURE 4
FIGURE 4
Effect of U. wallichiana on (A) cGMP concentration, (B) fluorescence intensity, (C) myocardial fibrosis, (D) relative cell surface area, and (E) relative mRNA expression level of ANP, BNP, IL-6, NOS3, TNF-α, TGFβ1, MMP9, β1 adrenergic receptor (β1 AR), ACE2 and Mas in ISO induced cardiac hypertrophy in wistar rats. Data were analyzed by using one-way ANOVA followed by Newman–Keuls Multiple comparison test. Data are shown as Mean ± SEM, α, control vs. ISO; β, ISO vs. EE; γ, ISO vs. BF; P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.
FIGURE 5
FIGURE 5
Representative photomicrographs of heart dyed with haematoxylin and eosin (H&E) stain (10× and 40× magnification). (A) Control, (B) ISO, (C) ISO+EE, (D) ISO+BF groups, respectively.
FIGURE 6
FIGURE 6
Schematic diagram showing the mechanism of action of EE and BF of U. wallichiana in ISO induced cardiac hypertrophy. ACE, angiotensin converting enzyme; cGMP, cyclic guanosine monophosphate; NOS, nitric oxide synthase.

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