Salvianolic acid A from Danhong Injection induces vasorelaxation by Regulating L-type calcium channel in isolated mouse arteries

Lin, Yuan; Chen, Yijun; Li, Jieyi; Chen, Yulin; He, Dong; Zuo, Rui; Xiao, Min-Jun; Xu, Danping; Zheng, Chaoyang; Wang, Wei; He, Rong‐Rong; Chen, Yang

doi:10.1016/j.jep.2022.115431

Cited by 10 publications

(4 citation statements)

References 39 publications

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“…Despite Danshen's clinical use for hypertension management, there is a notable gap in animal studies exploring its blood pressure-lowering effects using an Ang II-induced hypertension model (30)(31)(32)(33). Sal A has demonstrated vasodilatory properties in vitro through the inhibition of L-type calcium channel signaling in smooth muscle cells, and its antihypertensive efficacy in vivo remains unclear (34). A study on spontaneously hypertensive rats indicated that Sal A did not significantly lower blood pressure, which could be attributed to the low dosage and limited data from a single time-point blood pressure assessment (35).…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid a Attenuates Angiotensin Ii-Induced Cardiac Fibrosis Through Regulating the Txnip Signaling Pathway

Ye,

Wang,

et al. 2024

Shock

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Cardiac fibrosis, characterized by excessive collagen accumulation in heart tissues, poses a significant clinical challenge in various heart diseases and complications. Although salvianolic acid A (Sal A) from Danshen (Salvia miltiorrhiza) has shown promise in the treatment of ischemic heart disease, myocardial infarction, and atherosclerosis, its effects on cardiac fibrosis remain unexplored. Our study investigated the efficacy of Sal A in reducing cardiac fibrosis and elucidated its underlying molecular mechanisms. We observed that Sal A demonstrated significant cardioprotective effects against Angiotensin II (Ang II)-induced cardiac remodeling and fibrosis, showing a dose-dependent reduction in fibrosis in mice and suppression of cardiac fibroblast proliferation and fibrotic protein expression in vitro. RNA sequencing revealed that Sal A counteracted Ang II-induced upregulation of Txnip, and subsequent experiments indicated that it acts through the inflammasome and ROS pathways. These findings establish the anti-fibrotic effects of Sal A, notably attenuated by Txnip overexpression, and highlight its significant role in modulating inflammation and oxidative stress pathways. This underscores the importance of further research on Sal A and similar compounds, especially regarding their effects on inflammation and oxidative stress, which are key factors in various cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Salvianolic Acid a Attenuates Angiotensin Ii-Induced Cardiac Fibrosis Through Regulating the Txnip Signaling Pathway

Ye,

Wang,

et al. 2024

Shock

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“…Impaired endothelium-dependent vasodilation has been implicated in the development of PE. Danshensu directly acts on vascular endothelial and smooth muscle cells to promote vascular relaxation (Wang et al, 2013;Lin et al, 2022). It also dilates the vessels and improves blood circulation to increase renal blood flow and improve renal function in PE rats (Peng and Huang, 2021).…”

Section: Vasodilationmentioning

confidence: 99%

Effects of Salvia miltiorrhiza active compounds on placenta-mediated pregnancy complications

Kong

Li²,

Li³

et al. 2023

Front. Cell Dev. Biol.

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Placenta-mediated pregnancy complications (PMPCs), including preeclampsia (PE), fetal growth restriction (FGR), and recurrent spontaneous abortion (RSA), occur in approximately 5% of pregnancies and are caused by abnormal placenta development. The development of effective therapies for PMPCs is still challenging due to the complicated pathogenesis, such as disrupted vascular homeostasis and subsequent abnormal placentation. Synthetic drugs have been recommended for treating PMPCs; however, they tend to cause adverse reactions in the mother and fetus. Salvia miltiorrhiza (S. miltiorrhiza) has potential effects on PMPCs owing to its advantages in treating cardiovascular disorders. S. miltiorrhiza and its active compounds could attenuate the symptoms of PMPCs through anticoagulation, vasodilation, antioxidation, and endothelial protection. Thus, in this review, we summarize the literature and provide comprehensive insights on S. miltiorrhiza and its phytochemical constituents, pharmacological activities, and on PMPCs, which would be valuable to explore promising drugs.

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“…The data show that SA is an EV71 3C pro orthosteric site inhibitor with high antiviral activity. Importantly, two SA-rich Chinese drug agents, DanShenDiWan and FuFangDanShenPian, have been marketed and used for decades as a treatment for angina pectoris, and Danhong injection (containing SA) has entered the clinic for the treatment of stroke in China (Lin et al, 2022), suggesting that SA has good biosafety. Therefore, the development of SA as an antiviral agent would be more economic than innovative drug development.…”

Section: Introductionmentioning

confidence: 99%

Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection

Shi

Xie²,

Ma³

et al. 2023

Front. Pharmacol.

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Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by enterovirus (EV) infection. EV71 is one of the major pathogens causing hand, foot, and mouth disease and is more likely to cause exacerbation and death than other enteroviruses. Although a monovalent vaccine for EV71 has been developed, there are no clinically available anti-EV71 specific drugs. Here, we performed virtual screening and biological experiments based on the traditional Chinese medicine monomer library. We identified a traditional Chinese medicine monomer, Salvianolic acid A (SA), a polyphenolic compound isolated from Salvia miltiorrhiza. Salvianolic acid A inhibits EV71 virus infection in a concentration-dependent manner, and its antiviral activity is higher than that of other reported natural polyphenols and has a high biosafety. Furthermore, molecular dynamics simulations showed that salvianolic acid A can anchor to E71, a member of the enzyme catalytic triad, and cause H40 to move away from the catalytic center. Meanwhile, molecular mechanics generalized born surface area (MMGBSA) and steered molecular dynamics (SMD) results showed that the P1 group of SA was most easily unbound to the S1 pocket of 3Cpro, which provided theoretical support to further improve the affinity of salvianolic acid A with 3Cpro. These findings suggest that salvianolic acid A is a novel EV71 3Cpro inhibitor with excellent antiviral activity and is a promising candidate for clinical studies.

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Salvianolic acid A from Danhong Injection induces vasorelaxation by Regulating L-type calcium channel in isolated mouse arteries

Cited by 10 publications

References 39 publications

Salvianolic Acid a Attenuates Angiotensin Ii-Induced Cardiac Fibrosis Through Regulating the Txnip Signaling Pathway

Salvianolic Acid a Attenuates Angiotensin Ii-Induced Cardiac Fibrosis Through Regulating the Txnip Signaling Pathway

Effects of Salvia miltiorrhiza active compounds on placenta-mediated pregnancy complications

Computational and experimental studies of salvianolic acid A targets 3C protease to inhibit enterovirus 71 infection

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