Cardioprotective potential of amygdalin against angiotensin II induced cardiac hypertrophy, oxidative stress and inflammatory responses through modulation of Nrf2 and NF‐κB activation

Abstract

Heart failure (HF) and cardiac hypertrophy is an unfavorable outcome of pathological cardiac remodeling and represents the most important contributing factor for HF and cardiac hypertrophy. Amygdalin (AMG) is a cyanogenic glycoside derived from bitter almonds. Accumulating evidences have highlighted their pharmacological potentials against various diseases. However, there is no report delineating the potential of AMG against angiotensin (Ang II) induced cardiac injuries. Thus, the present study was performed to explore whether AMG could ameliorate Ang II induced cardiomyopathies and thereby ascertain the underlying mechanisms thereof. To this end, H9c2 cells were treated with Ang II and thereafter treated with various concentration of AMG and finally the cardio‐protective effects of AMG were analyzed through Western blotting, immunofluorescence, and insilico analysis. Our results showed that the cardiomyocyte cell size, inflammatory markers and cytokines(pNF‐κB, TNF‐α, iNOS and COX‐2) were markedly increased following Ang II treatment; nevertheless, treatment with AMG led to considerable decrement in the Ang II induced enlargement of the cardiomyocytes, and attenuate the expression of hypertrophic markers(ANP, BNP and MHC‐7), inflammatory markers and cytokines. Additionally, oxidative stress related proteins (Nrf2, catalase, SOD‐2, and GPX‐4) were markedly increased following AMG treatment. Molecular docking reveals the interaction of AMG with Nrf2 possessing good binding affinity. Cumulatively, our study highlights the cardio‐protective role of AMG against Ang II induced cardiomyopathies, including oxidative stress and inflammation effects. The intriguing in vitro results warrants the need of further animal studies to truly ascertain their potentialities.

Effects and Mechanisms of Taohong Siwu Decoction on the Prevention and Treatment of Myocardial Injury

“…However, there are still some limitations and uncertainties in the research of prescriptions. According to the current research, THSWD contains many active ingredients (Wu, 2011;Li and Guo, 2016;Wang and Peng, 2017;WangChen and Han, 2019;Zhao and Liu, 2019;Nie and Cheng, 2020), including ligustilide, catalpol, paeoniflorin (Zhang et al, 2012;Zhou et al, 2013;Chen et al, 2018b;Qian et al, 2015;Zhai and Guo, 2016;Liu et al, 2019b;Liu et al, 2020), paeonional lactonine, amygdalin (Kung et al, 2021), kaempferol (Zhou et al, 2015;Feng et al, 2017;Chen et al, 2018a), quercetin (Ruiz et al, 2015;Roslan et al, 2017;Patel et al, 2018;Chen et al, 2020), paeonol, ferulic acid (Dai and Wu, 2017), benzoic acid, coumaric acid, caffeic acid, gallic acid, and hydroxysafflor yellow A (Song et al, 2005;Ji et al, 2008;Ji et al, 2009), etc., (Table 2). However, the molecular biological mechanism of which or several components play a role needs to be further studied and elucidated.…”

“…In studies of the effective components of THSWD, ferulic acid can activate the signal pathways of transcription factor NF-E2 related factor 2 (Nrf2), phosphatidylinositol 3-kinase (PI3K) and extracellular regulated protein kinases (ERK) to play an antioxidant role, thus protecting vascular endothelial cells from oxidative damage (Ma et al, 2010). Cardioprotective potential of amygdalin from Persicae semen could inhibit cardiac hypertrophy, oxidative stress and inflammatory responses through modulation of Nrf2 and NF-κB activation (Kung et al, 2021). Paeoniflorin can also reduce the expression of related mRNA (Zhou et al, 2013;, inhibit NF-kB signaling pathway and activate PI3K/Akt signaling pathway (Zhai and Guo, 2016), thereby exerting anti-inflammatory and anti-oxidation effects.…”

Inflammation, It’s Regulation and Antiphlogistic Effect of the Cyanogenic Glycoside Amygdalin

“…COX-2 mRNA expression was more efficiently downregulated by this glycoside compared to COX-1 mRNA expression. A research team led by Kunga [ 147 ] highlighted the ability of amygdalin to inhibit, in a dose-dependent manner, TNF-α expression, inducible nitric oxide synthase, and COX-2, as well as NF-κB protein expression, and increased the levels of oxidative stress-related proteins, e.g., nuclear factor-erythroid-2-related factor 2 (Nrf2). This is because COX-2 activity is associated with nitric oxide (NO) radicals formed based on NO synthase activity, and, as mentioned, amygdalin inhibits it, thus indirectly suppressing the production of PGE 2 , the main metabolite of COX-2 [ 148 ].…”

Cardioprotective effects of transplanted adipose‐derived stem cells under Ang II stress with Danggui administration augments cardiac function through upregulation of insulin‐like growth factor 1 receptor in late‐stage hypertension rats

“…Notably, apoptosis of cardiomyocytes in prolonged stress situations is a prominent cause of heart dysfunction and death associated with aging 3 . Increased level of the vasoconstrictor angiotensin‐II (Ang II) has an important role in the pathological hypertension condition in cardiovascular diseases, and evidence support that the autocrine and paracrine signaling of Ang II is related to the enhancement of cardiomyocyte hypertrophy and apoptosis 4,5 . An elevated level of these neurohumoral mediators also enhances interstitial and perivascular fibrosis.…”

“…3 Increased level of the vasoconstrictor angiotensin-II (Ang II) has an important role in the pathological hypertension condition in cardiovascular diseases, and evidence support that the autocrine and paracrine signaling of Ang II is related to the enhancement of cardiomyocyte hypertrophy and apoptosis. 4,5 An elevated level of these neurohumoral mediators also enhances interstitial and perivascular fibrosis. Hence, this high amount of cardiac Ang II exerts hemodynamic effects that further causes hypertrophic response.…”