Protective effect of Di'ao Xinxuekang capsule against doxorubicin-induced chronic cardiotoxicity

Li, Xiaofen; Liang, Jiyi; Qin, Anquan; Wang, Tao; Liu, Sili; Li, Wei; Yuan, Chuqiao; Qu, Liping; Zhou, Wenjun

doi:10.1016/j.jep.2021.114943

Cited by 21 publications

(9 citation statements)

References 28 publications

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“…In Traditional Chinese Medicine theory, it has the effects of promoting blood circulation, and removing blood stasis which might explain its therapeutic effect in CADs. Modern pharmacological studies have shown that DXXK has the effects of anti-myocardial ischaemia, blood lipid lowering, anti-atherosclerosis, platelet aggregation prevention, inflammation inhibition, and antioxidative stress effects ( Dong G. X. et al, 2017 ; Zhang weizhi and Chen, 2020 ; Li et al, 2021a ). Our previous research has shown that DXXK can alleviate hyperlipidemia, fat accumulation, and atherosclerosis formation in ApoE −/− mice fed a high-fat diet (HFD), and reduce the expression of liver PCSK9 and LDLR ( Qu et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Di’ao Xinxuekang Capsule Improves the Anti-Atherosclerotic Effect of Atorvastatin by Downregulating the SREBP2/PCSK9 Signalling Pathway

Liang

Liu

et al. 2022

Front. Pharmacol.

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Statins are the first choice for lowering low-density lipoprotein cholesterol (LDL-C) and preventing atherosclerotic cardiovascular disease (ASCVD). However, statins can also upregulate proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn might limits the cholesterol-lowering effect of statins through the degradation of LDL receptors (LDLR). Di’ao Xinxuekang (DXXK) capsule, as a well-known traditional Chinese herbal medicine for the prevention and treatment of coronary heart disease, can alleviate lipid disorders and ameliorate atherosclerosis in atherosclerosis model mice and downregulate the expression of PCSK9. In this study, we further explored whether DXXK has a synergistic effect with atorvastatin (ATO) and its underlying molecular mechanism. The results showed that both ATO monotherapy (1.3 mg/kg) and ATO combined with DXXK therapy significantly lowered serum lipid levels and reduced the formation of atherosclerotic plaques and the liver lipid accumulation. Moreover, compared with ATO monotherapy, the addition of DXXK (160 mg/kg) to the combination therapy further lowered LDL-C by 15.55% and further reduced the atherosclerotic plaque area by 25.98%. In addition, the expression of SREBP2, PCSK9 and IDOL showed a significant increase in the model group, and the expression of LDLR was significantly reduced; however, there were no significant differences between the ATO (1.3 mg/kg) and the model groups. When ATO was combined with DXXK, the expression of LDLR was significantly increased and was higher than that of the model group and the expression of SREBP2 and PCSK9 in the liver was also significantly inhibited. Moreover, it can be seen that the expression of SREBP2 and PCSK9 in the combination treatment group was significantly lower than that in the ATO monotherapy group (1.3 mg/kg). Besides, the expression of IDOL mRNA in each treatment group was not significantly different from that of the model group. Our study suggests that DXXK might have a synergistic effect on the LDL-C lowering and antiatherosclerosis effects of ATO through the SREBP2/PCSK9 pathway. This indicates that a combination of DXXK and ATO may be a new treatment for atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Di’ao Xinxuekang Capsule Improves the Anti-Atherosclerotic Effect of Atorvastatin by Downregulating the SREBP2/PCSK9 Signalling Pathway

Liang

Liu

et al. 2022

Front. Pharmacol.

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“…One of the earliest adaptive cardiac tissue responses during DOX is releasing of HIF-1α 38 that could stimulate gene transcription of another protective agent; VEGF. The latter has an important role in preserving the vasculature and protecting the tissue against the associated ischemic damage.…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase inhibitor, Vinpocetine, guards against doxorubicin induced cardiotoxicity via modulation of HIF/VEGF and cGMP/cAMP/SIRT signaling pathways

et al. 2022

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Purpose: Doxorubicin (DOX) is a widely used chemotherapeutic agent complicated with cardiotoxic adverse effects. Up till now, there are no researches discussing the role of vinpocetine (VIN) in DOX cardiotoxicity. Thus, the aim of our work was to study this effect and explore the different involved mechanisms. Methods: 50 male Wistar albino rats were subjected to DOX toxicity via administration of single i.p. Dose (15 mg/kg) on the 4th day with or without co-administration of VIN (10, 20, 30 mg/kg/day) orally for 5 days. Results: Our data revealed that VIN succeeded in protecting the heart against DOX induced damage as manifested by significant decrease of cardiac enzymes, hypoxia inducible factor alpha (HIF-1α), vascular endothelial growth factor-A (VEGF-A), tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and caspase3 levels. Furthermore, VIN given group showed marked improvement of the histopathological changes of cardiac injury, total antioxidant capacity (TAC), elevation of reduced glutathione (GSH), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) and sirtuin-1 (SIRT-1). Conclusion: We concluded that VIN could ameliorate DOX induced cardiac damage and this effect may be attributed to modulation of HIF/VEGF signaling pathway, up-regulation of cGMP/cAMP/SIRT pathway, inhibition of phosphodiesterase enzyme, besides its anti-apoptotic, anti-inflammatory, and anti-oxidant properties.

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“…A recent study demonstrated that ferroptosis occurs mainly in the phase of myocardial reperfusion but not ischemia. The ferroptosis was evaluated with the levels of ACSL4, GPX4, iron, and MDA [ 17 , 25 , 26 ]. An iron chelator (deferoxamine) was used to verify the contribution of ferroptosis on IRI.…”

Section: Cardiac Ferroptosismentioning

confidence: 99%

Cardiomyocyte Damage: Ferroptosis Relation to Ischemia-Reperfusion Injury and Future Treatment Options

Laukaitienė

Gujytė

Kaduševičius

2023

IJMS

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About half a century ago, Eugene Braunwald, a father of modern cardiology, shared a revolutionary belief that “time is muscle”, which predetermined never-ending effort to preserve the unaffected myocardium. In connection to that, researchers are constantly trying to better comprehend the ongoing changes of the ischemic myocardium. As the latest studies show, metabolic changes after acute myocardial infarction (AMI) are inconsistent and depend on many constituents, which leads to many limitations and lack of unification. Nevertheless, one of the promising novel mechanistic approaches related to iron metabolism now plays an invaluable role in the ischemic heart research field. The heart, because of its high levels of oxygen consumption, is one of the most susceptible organs to iron-induced damage. In the past few years, a relatively new form of programmed cell death, called ferroptosis, has been gaining much attention in the context of myocardial infarction. This review will try to summarize the main novel metabolic pathways and show the pivotal limitations of the affected myocardium metabolomics.

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Protective effect of Di'ao Xinxuekang capsule against doxorubicin-induced chronic cardiotoxicity

Cited by 21 publications

References 28 publications

Di’ao Xinxuekang Capsule Improves the Anti-Atherosclerotic Effect of Atorvastatin by Downregulating the SREBP2/PCSK9 Signalling Pathway

Di’ao Xinxuekang Capsule Improves the Anti-Atherosclerotic Effect of Atorvastatin by Downregulating the SREBP2/PCSK9 Signalling Pathway

Phosphodiesterase inhibitor, Vinpocetine, guards against doxorubicin induced cardiotoxicity via modulation of HIF/VEGF and cGMP/cAMP/SIRT signaling pathways

Cardiomyocyte Damage: Ferroptosis Relation to Ischemia-Reperfusion Injury and Future Treatment Options

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