Schisantherin A causes endothelium-dependent and -independent vasorelaxation in isolated rat thoracic aorta

Yang, Shuo; Xu, Zhiwei; Lin, Chengcheng; Li, He; Sun, Jia; Chen, JianGuang; Wang, Chunmei

doi:10.1016/j.lfs.2020.117357

Cited by 14 publications

(14 citation statements)

References 18 publications

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“…A vasorelaxant effect can be achieved by an endothelium-dependent (indirect vasodilators) or a non-endothelium-dependent (direct vasodilators) mechanism. In fact, endothelium-dependent vasorelaxation is mediated by endothelium-derived vasodilator factors, such as endothelium-derived hyperpolarizing factor, prostacyclin (PGI 2 ), and NO [ 48 , 49 ]. In other to get more insight into the vasorelaxant mechanism of the plant extracts, they were tested on aortic rings without endothelium and on aortic rings preincubated with L-NAME, an inhibitor of nitric oxide synthase.…”

Section: Discussionmentioning

confidence: 99%

Vasorelaxant and Antioxidant Effects of Aframomum pruinosum Gagnep. (Zingiberaceae) Seed Extracts May Mediate Their Cardioprotective Activity against Isoproterenol-Induced Myocardial Infarction

Nguelefack‐Mbuyo

Nokam

Tchinda

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Aframomum pruinosum seeds are traditionally used in Cameroon to treat cardiac palpitations. The present work evaluates the cardioprotective effects of the aqueous (AE) and ethanolic (EE) extracts from A. pruinosum seeds against isoproterenol-induced myocardial infarction. Male Wistar rats were pretreated for 14 days with AE or EE at doses of 75 and 150 mg/kg/day or propranolol (10 mg/kg/day). On days 15 and 16, they were injected subcutaneously with isoproterenol (85 mg/kg/day). Blood pressure and heart rate were weekly recorded by tail-cuff plethysmography during pretreatment and 24 hours after the second dose of isoproterenol. At the end of the treatment period, serum Lactate Dehydrogenase (LDH), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), cardiac nitric oxide (NO), myeloperoxidase (MPO), and oxidative stress parameters (SOD, catalase, MDA, and GSH) were assayed. Sections of left ventricle tissue were subjected to histological analysis. The vasorelaxant effects of cumulative concentrations of AE or EE (3–300 µg/mL) were evaluated on intact or endothelium-denuded isolated aorta rings precontracted with noradrenaline (1 µM). The vasorelaxant effects of the plant extracts were also tested in the presence of Nω-nitro-L-arginine methyl ester (L-NAME; 100 µM). AE and EE significantly prevented blood pressure decrease and heart rate increase elicited by isoproterenol. Both plant extracts inhibited the increase in ALT, AST, NO, and MPO but did not prevent LDH surge. Oxidative stress parameters were improved following A. pruinosum pretreatment. AE and EE highly reduced cardiomyocyte necrosis and fibrosis but did not prevent leukocyte infiltration. Both extracts induced a concentration-dependent vasorelaxation that was significantly inhibited by the destruction of the endothelium and by L-NAME. Extracts of A. pruinosum exhibited cardioprotective effects, and EE was the most active. The cardioprotective effects of A. pruinosum extracts could be ascribed to their antioxidant, antinecrotic, and endothelium-dependent vasorelaxant effects.

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Section: Discussionmentioning

confidence: 99%

Vasorelaxant and Antioxidant Effects of Aframomum pruinosum Gagnep. (Zingiberaceae) Seed Extracts May Mediate Their Cardioprotective Activity against Isoproterenol-Induced Myocardial Infarction

Nguelefack‐Mbuyo

Nokam

Tchinda

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Moreover, isorhamnetin inhibited IP 3 -sensitive calcium pools from releasing calcium and protected endothelial cells (Jiayi et al, 2019). Schisantherin A (SCA) regulates NO and prostacyclin (PGI2) to induce endothelium-dependent vasodilation and obstructs VDCC to promote endothelium-independent vasodilation (Yang et al, 2020b). Thus, TCM can treat certain CVD conditions such as hypertensive heart disease by maintaining proper endothelial cell function through regulation of the calcium signaling pathway (Xiong et al, 2013;Yu et al, 2013;Zhang et al, 2020) (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the disturbance of calcium homeostasis has been observed in numerous types of CVDs, such as cardiac arrhythmias (Landstrom et al, 2017). Various studies have shown that Chinese herbal medicines and their active ingredients can improve cardiomyocyte function and treat CVDs by regulating the expression and activity of calcium channels and receptors (Hu et al, 2012;Yang et al, 2020b;Liu et al, 2013) (Figure 1). For example, senkyunolide A and ligustrazinecan hindered the opening of VDCC, rendering a calcium antagonistic effect (Lei et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Traditional Chinese Medicine on Cardiovascular Diseases: the Central Role of Calcium Signaling

Zhang

et al. 2021

Front. Pharmacol.

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Calcium, as a second messenger, plays an important role in the pathogenesis of cardiovascular diseases (CVDs). The malfunction of calcium signaling in endothelial cells and vascular smooth muscle cells promotes hypertension. In cardiomyocytes, calcium overload induces apoptosis, leading to myocardial infarction and arrhythmias. Moreover, the calcium–calcineurin–nuclear factor of activated T cells (NFAT) pathway is essential for expressing the cardiac pro-hypertrophic gene. Heart failure is also characterized by reduced calcium transient amplitude and enhanced sarcoplasmic reticulum (SR) calcium leakage. Traditional Chinese medicine (TCM) has been used to treat CVDs for thousands of years in China. Because of its multicomponent and multitarget characteristics, TCM's unique advantages in CVD treatment are closely related to the modulation of multiple calcium handling proteins and calcium signaling pathways in different types of cells involved in distinct CVDs. Thus, we systematically review the diverse mechanisms of TCM in regulating calcium pathways to treat various types of CVDs, ranging from hypertrophic cardiomyopathy to diabetic heart disease.

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“…The present study is the first to investigate the vasodilatory effect of GPS in Vasodilation can be divided into two types: endotheliumdependent and endothelium-independent. The former is mainly related to the production of endothelium-derived relaxing factor NO and prostaglandins in the thoracic aorta, while the latter is related to a reduction in [Ca 2+ ] in levels caused by drugs directly acting on VSM [29]. Contraction of VSM depends on the influx of extracellular Ca 2+ through VDCC and ROCC in the cell membrane and the release of intracellular Ca 2+ through stimulation of IP 3 R-and RYRmediated Ca 2+ channels in the sarcoplasmic reticulum [30].…”

Section: Discussionmentioning

confidence: 99%

Gentiopicroside Produces Endothelium‐Independent Vasodilation by Deactivating the PI3K/Akt/Rho‐Kinase Pathway in Isolated Rat Thoracic Aorta

Xing

Nong

Qin

et al. 2021

BioMed Research International

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Gentiopicroside (GPS), a main active secoiridoid glucoside derived from the roots of perennial herbs in the Gentianaceae family, has antispasmodic and relaxant effects. However, the vasorelaxant effects of GPS on aortic rings and the molecular mechanisms involved in these effects are not yet clear. Therefore, we investigated whether GPS inhibits phenylephrine- (PE-) or KCl-induced contractions in isolated rat thoracic aortic rings. The present study found that GPS produced a dose-dependent relaxation in aortic rings precontracted with PE or KCl and significantly reduced CaCl2-, narciclasine- (Rho-kinase activator-), and phorbol-12,13-diacetate- (PKC activator-) induced vasocontractions. Pretreatment with NG-Nitroarginine methyl ester hydrochloride (L-NAME, NOS inhibitor), methylene blue (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (KV channel inhibitor), and glibenclamide (KATP channel inhibitor) had no influence on the vasorelaxant effect of GPS, while BaCl2 (Kir channel inhibitor), tetraethylammonium chloride (KCa channel inhibitor), ruthenium red (RYR inhibitor), and heparin (IP3R inhibitor) significantly reduced GPS-induced vasorelaxation. Moreover, GPS pretreatment remarkably inhibited the influx of Ca2+ in vascular smooth muscle cells stimulated using KCl or PE-containing CaCl2 solution. Western blot analysis confirmed that GPS treatment inhibited PE-induced increases in the protein levels of p-Akt, p-myosin light chain (MLC), and p-myosin-binding subunit of myosin phosphatase 1 (MYPT1) in the aortic rings. Additionally, the vasorelaxation activity of GPS was attenuated upon pretreatment with LY294002 (PI3K/Akt inhibitor), Y27632 (Rho-kinase inhibitor), and verapamil (L-type Ca2+ channel inhibitor). These findings demonstrate that GPS exhibits endothelium-independent vasorelaxant effects through inhibition of voltage-dependent, receptor-operated, and inositol triphosphate receptor (IP3R)/ryanodine receptor- (RYR-) mediated Ca2+ channels as well as the PI3K/Akt/Rho-kinase signaling pathway.

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Schisantherin A causes endothelium-dependent and -independent vasorelaxation in isolated rat thoracic aorta

Cited by 14 publications

References 18 publications

Vasorelaxant and Antioxidant Effects of Aframomum pruinosum Gagnep. (Zingiberaceae) Seed Extracts May Mediate Their Cardioprotective Activity against Isoproterenol-Induced Myocardial Infarction

Vasorelaxant and Antioxidant Effects of Aframomum pruinosum Gagnep. (Zingiberaceae) Seed Extracts May Mediate Their Cardioprotective Activity against Isoproterenol-Induced Myocardial Infarction

Therapeutic Effects of Traditional Chinese Medicine on Cardiovascular Diseases: the Central Role of Calcium Signaling

Gentiopicroside Produces Endothelium‐Independent Vasodilation by Deactivating the PI3K/Akt/Rho‐Kinase Pathway in Isolated Rat Thoracic Aorta

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