Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

Lu, Chen; X, Guo; He, Xianghui; Yu, Chang Yeon; Zheng, Fa; Xu, Chenji; Zhang, Shuwen; Zhou, Yongqiang; Li, Junfang

doi:10.1016/j.jsps.2022.04.005

Cited by 10 publications

(7 citation statements)

References 44 publications

(115 reference statements)

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“…Since MIRI is the main cause of deterioration of cardiac function after coronary bypass or myocardial infarction, much attention has been paid to the search for effective drugs to treat this type of disease (Arslan et al, 2010). In previous work, SIN has shown ex vivo protection against arrhythmia, oxidative stress, and inflammation in a rat model of MIRI (Xie and Jin, 1993;Zhang et al, 2021;Lu et al, 2022). However, the isolated heart cannot fully represent the heart in vivo under normal physiological conditions because it is not regulated by the sympathetic nervous system, parasympathetic nervous system, and renin-angiotensin-aldosterone system (RAAS) (Papa, 2020;Martin et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Although previous studies have confirmed the anti-oxidative stress and anti-inflammatory properties of SIN in MIRI ex vivo ( Xie and Jin, 1993 ; Lu et al, 2022 ), the in vivo function of SIN in MIRI has not yet been elucidated. We propose that administration of SIN may be able to prevent ischemia/reperfusion-induced cardiac injury by preventing oxidative stress, cellular apoptosis, and inflammation in vivo .…”

Section: Introductionmentioning

confidence: 95%

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Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation

Xia

et al. 2022

Front. Pharmacol.

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Sinomenine (SIN), an alkaloid extracted from the root of S. acutum. sinomenine, has been shown to have antiarrhythmic, antioxidant, and anti-inflammatory effects in myocardial ischemia-reperfusion injury (MIRI) ex vivo. In this study, we investigated the cardioprotective effects of SIN in an in vivo mouse model of MIRI. Adult male C57BL/6J mice received SIN (80 mg/kg) for 5 days and underwent 30 min of percutaneous occlusion of the left anterior descending artery (LAD) followed by 24 h of reperfusion. Results showed that pretreatment with SIN significantly reduced myocardial infarct size and concentrations of markers of cardiac injury and improved left ventricular ejection fraction (EF) and shortening fraction (FS) in MIRI mice. The SIN pretreatment prevented the MIRI-induced decrease in the expression levels of Bcl-2, increase in the expression levels of caspase-3, caspase-9, and Bax, and increase in the number of TUNEL-positive cells in ischemic heart tissue. It was also found that pretreatment with SIN prevented the MIRI-induced oxidative stress imbalance in ischemic heart tissue, as shown by the increase in total antioxidant capacity (T-AOC) and glutathione (GSH) and the decrease in malondialdehyde (MDA), reactive oxygen species (ROS), and dihydroethidium (DHE) density. Further studies showed that the stimulus of cardiac ischemia/reperfusion caused a remarkable increase in the expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA in ischemic heart tissue, which was effectively prevented by pretreatment with SIN. These results demonstrate that SIN can attenuate MIRI-induced cardiac injury in vivo by preventing oxidative stress, inflammation, and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation

Xia

et al. 2022

Front. Pharmacol.

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“…Lu and associates described the protective effect of SIN on myocardial ischemia-reperfusion (I/R) injury in rats. Markers of myocardial injury and levels of C-reactive protein (Hs-CRP), MCP-1, TNF-α, IL-1β, and IL-6 were reduced, leading to the amelioration of I/R injury in rats [ 205 ]. The specific points of the cardiovascular tissue protection activity of SIN are summarized in Table 11 .…”

Section: Organs Protectionmentioning

confidence: 99%

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

Hou,

Huang,

Huang

et al. 2024

Molecules

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Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of approximately 121.4 nM against PC-3 and DU-145 cells, primarily through the PI3K/Akt/mTOR, NF-κB, MAPK, and JAK/STAT signaling pathways. Additionally, they manifest anti-inflammatory and analgesic effects predominantly via the NF-κB, MAPK, and Nrf2 signaling pathways. Utilized in treating rheumatic arthritis, these alkaloids also play a significant role in cardiovascular and cerebrovascular protection, as well as organ protection through the NF-κB, Nrf2, MAPK, and PI3K/Akt/mTOR signaling pathways. This review concludes with perspectives and insights on this topic, highlighting the potential of sinomenine-related compounds in clinical applications and the development of medications derived from natural products.

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“…This effect is attributed to modulation of the OS pathway, leading to a significant reduction in myocardial infarct size and myocardial injury markers in MI/R-injured mice [ 292 ]. SIN also improves antioxidant parameters, such as MDA, SOD, CAT, and GPX levels, and inhibits the levels of CK, CK-MB, and troponin I in MI/R-injured rats, thereby exerting anti-arrhythmic effects against OS volatiles [ 293 ]. Studies further demonstrate that SIN reduces apoptosis rates, ROS levels, and MDA expression by activating the Nrf2/ARE signaling pathway, thereby attenuating OS associated with cardiac hypertrophy [ 294 ].…”

Section: Other Types Of Herbal Monomers With Antioxidant Activitymentioning

confidence: 99%

Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease

Yan

Sun

et al. 2023

J Transl Med

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Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment. Graphical Abstract

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Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

Cited by 10 publications

References 44 publications

Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation

Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease

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