Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from<i>Rhizoma Chuanxiong</i>): Roles and Mechanisms

Guo, Ming; Liu, Yue; Shi, Dazhuo

doi:10.1155/2016/2430329

Cited by 95 publications

(61 citation statements)

References 56 publications

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“…They lyse blood clot, dilate coronary arteries, inhibit platelet aggregation, scavenge free radicals, improve microcirculation and have anti-inflammatory properties. 6,7) Both of them are widely used in clinic for treatment of cardiovascular diseases. Although widely used, their therapeutic benefits are severely limited due to weak activities.…”

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confidence: 99%

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

Zhang¹,

Hu²,

Luo³

et al. 2017

Biological & Pharmaceutical Bulletin

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In this study, we investigated the cardioprotective mechanisms of action of DT-010, a novel danshensutetramethylpyrazine conjugate. DT-010 significantly preserved cell viability and suppressed cell apoptosis in H9c2 cells injured by tert-butylhydroperoxide (t-BHP), iodoacetic acid (IAA) and hypoxia-reoxygenation. In addition, DT-010 pre-treatment reduced the intracellular level of free radicals including superoxide anion (·O 2 ), hydroxyl radical (·OH) and peroxynitrite anion (ONOO ) after t-BHP exposure. Moreover, DT-010 up-regulated the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) as well as mitochondrial transcription factor A (Tfam) and heme oxygenase-1 (HO-1) in H9c2 cells. DT-010 also triggered Nrf2 nuclear translocation. In a rat myocardial ischemia-reperfusion model, DT-010 significantly alleviated myocardial infarction. The results indicated that DT-010 may be a promising candidate for the treatment of cardiovascular diseases, particularly myocardial ischemia and reperfusion injury.Key words Danshensu derivative; oxidative stress; apoptosis; myocardial ischemia reperfusion injury; peroxisome proliferator-activated receptor gamma coactivator 1 alpha/nuclear factor-E2-related factor 2/heme oxygenase-1 (PGC-1α/Nrf2/HO-1) pathway Myocardial ischemia is a primary cause of sudden death worldwide. Myocardial ischemia results from a decreased blood flow to the heart, preventing the heart from receiving adequate supply of energy. The reduced blood flow is usually caused by a partial or complete blockade of the arteries. Traditional treatments focus on restoring blood supply, such as by pass-graft surgery, dilation of coronary artery and coronary thrombolysis, and etc. 1) Although restoration of blood flow to the ischemic heart tissues is important, it is not adequate because myocardial ischemic damage is progressively developed following reperfusion due to an over-production of a large number of biospecies. 2,3) Compelling evidence demonstrated that free radicals generated during ischemia and reperfusion play pivotal roles in myocardial apoptosis. Free radical scavengers can effectively inhibit myocardial apoptosis. The previous studies have demonstrated that agents that combine anti-thrombolytic and anti-oxidative activities showed promising therapeutic efficacy in the treatment of myocardial ischemia. 4,5) In China, many traditional herbs have been used to prevent and treat myocardial ischemia. Among them are Salvia miltiorrhiza (Danshen) and Ligusticum wallichii (Chuanxiong). As the major active ingredients, (3-(3,4-dihydroxyphenyl) lactic acid) (Danshensu, DSS, Fig. 1) isolated from Danshen and tetramethylpyrazine (TMP, Fig. 1) isolated from Chuanxiong have a variety of biological activities. They lyse blood clot, dilate coronary arteries, inhibit platelet aggregation, scavenge free radicals, improve microcirculation and have anti-inflammatory properties. 6,7) Both of them are widely used in clinic for treatm...

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confidence: 99%

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

Zhang¹,

Hu²,

Luo³

et al. 2017

Biological & Pharmaceutical Bulletin

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“…For example, several systematic reviews have been conducted pertaining to salvianolic acid B (Wang J. et al, 2013), tetramethylpyrazine (Ming et al, 2016), Panax notoginseng saponins (Yang et al, 2014), etc. Among them, scutellarin, the principal component of breviscapine, is a type of monomer component of CHM and breviscapine has significant effects on vasodilation (improving erectile function); protection against I/R; anticoagulation and antithrombosis; reduction of smooth muscle cell migration and proliferation; anticardiac remodeling; antiarrhythmia, and reduction of blood lipids.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review

Gao

Chen

et al. 2017

Front. Pharmacol.

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Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz., containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply. Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, anticoagulation, antithrombosis, endothelial protection, myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction. In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for cardiovascular diseases (CVDs) including coronary heart disease, myocardial infarction, hypertension, atrial fibrillation, hyperlipidaemia, viral myocarditis, chronic heart failure, and pulmonary heart disease. However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications.

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“…TMP, which has also been synthesized, exerts vasodilative, anticoagulant, anti‐inflammatory and positive inotropic effects. TMP has been widely used for the treatment of cardiovascular diseases (Guo, Liu, & Shi, 2016), due to its long history of safe usage, high efficacy, low expense, few adverse effects, and easy oral administration (Bai et al, 2014; Chen & Chen, 1992; Fu et al, 2012; Shaw, Chen, & Tsai, 2013; Wang et al, 2013; Zeng et al, 2013; Zhu, Wang, & Qin, 2009). In the present context, the beneficial effects of TMP have been shown in hypoxia‐induced PH, as a pulmonary vasodilator and by normalizing the right ventricular hypertrophy and muscularization of pulmonary arterioles (Cai & Barer, 1989).…”

Section: Introductionmentioning

confidence: 99%

Tetramethylpyrazine: A promising drug for the treatment of pulmonary hypertension

Chen

Yang

et al. 2020

British J Pharmacology

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Background and Purpose: Tetramethylpyrazine (TMP) was originally isolated from the traditional Chinese herb ligusticum and the fermented Japanese food natto and has since been synthesized. TMP has a long history of beneficial effects in the treatment of many cardiovascular diseases. Here we have evaluated the therapeutic effects of TMP on pulmonary hypertension (PH) in animal models and in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).Experimental Approach: Three well-defined models of PH -chronic hypoxia (10% O 2 )-induced PH (HPH), monocrotaline-induced PH (MCT-PH) and Sugen 5416/hypoxia-induced PH (SuHx-PH) -were used in Sprague-Dawley rats, and assessed by echocardiography, along with haemodynamic and histological techniques. Primary cultures of rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to study intracellular calcium levels. Western blots and RT-qPCR assays were also used.In the clinical cohort, patients with PAH or CTEPH were recruited. The effects of TMP were evaluated in all systems.Key Results: TMP (100 mgÁkg −1 Áday −1 ) prevented rats from developing experimental PH and ameliorated three models of established PH: HPH, MCT-PH and SuHx-PH.The therapeutic effects of TMP were accompanied by inhibition of intracellular calcium homeostasis in PASMCs. In a small cohort of patients with PAH or CTEPH, oral Abbreviations: 2D, 2-dimensional; 6MWD, 6-min walking distance; Ccr, creatinine clearance; CTEPH, chronic thromboembolic pulmonary hypertension; EIP, End-inspiratory plateau pressure; FAC, Fractional area change; H&E, haematoxylin and eosin; HPH, hypoxia-induced pulmonary hypertension; HRR1, heart rate recovery at 1 min of rest; IPAH, idiopathic pulmonary arterial hypertension; KRBS, Krebs Ringer bicarbonate solution; LV, left ventricle; LVEF, left ventricular ejection fraction; LVFS, left ventricular fractional shortening; MCT, monocrotaline; mPAP, mean pulmonary arterial pressure; PA, pulmonary artery; PAD, pulmonary arterial diameter; PAH, pulmonary arterial hypertension; PAP, pulmonary arterial pressure; PASMC, pulmonary arterial smooth muscle cells; PAT, pulmonary arterial acceleration time; PET, pulmonary arterial ejection time; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RAD, right atrium diameter; RHC, right heart catheterization; ROCC, receptor-operated Ca 2+ channels; ROCE, receptor-operated Ca 2+ entry; RV, right ventricle; RVEDD, Right ventricular end diastolic diameter; RVEDWT, right ventricular end-diastolic free-wall thickness; RVSP, right ventricular systolic pressure; S, septum; SOCC, store-operated Ca 2+ channels; SOCE, store-operated Ca 2+ entry; SuHx-PH, Sugen/hypoxia-induced pulmonary hypertension; TAPSE, tricuspid annular plane systolic excursion; TMP, tetramethylpyrazine; VDCC, voltage-dependent Ca 2+ channels. administration of TMP (100 mg, t.i.d. for 16 weeks) increased the 6-min walk distance and improved the 1-min heart rate recovery.Conclusion and Implications: Our results s...

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Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated fromRhizoma Chuanxiong): Roles and Mechanisms

Cited by 95 publications

References 56 publications

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway

Therapeutic Effects of Breviscapine in Cardiovascular Diseases: A Review

Tetramethylpyrazine: A promising drug for the treatment of pulmonary hypertension

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