Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release

Cao, Yunxia; Zhang, Wei; He, Jianyu; He, Langchong; Xu, Cang‐Bao

doi:10.1016/j.vph.2006.05.004

Cited by 84 publications

(54 citation statements)

References 14 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An effective functional removal of the endothelium was indicated by absence of relaxation in response to Ach. The rings with endothelium showing <30% relaxation in response to Ach were discarded (7). Furthermore, the artery rings with endothelium were pre-incubated with the cyclooxygenase inhibitor Indo (5 µM), the guanylate cyclase inhibitor ODQ (10 µM), the endothelial nitric oxide (NO) synthase (eNOS) inhibitor L-NAME (100 μM), or with the with the K + channel blockers 4-AP (100 µM), BaCl 2 (10 µM), Gli (10 µM) or TEA (1 mM), respectively, for 20 min prior to addition of KCl (60 mM), followed by cumulative addition of Sim.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

Chen¹,

Zhang

Liu

et al. 2016

Biomedical Reports

View full text Add to dashboard Cite

Abstract. Independent of its lipid-lowering properties, simvastatin (Sim) induces vasorelaxation; however, the underlying mechanisms have remained elusive. The aim of the present study was to investigate the vasorelaxant effects of Sim on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro on a myograph. The results showed that Sim concentration-dependently relaxed the superior mesenteric artery rings with endothelium pre-contracted by phenylephrine hydrochloride [maximum relaxation (E max )=51.05±4.09%; negative logarithm of the concentration that caused 50% of the maximum response (pD 2 )=4.17±0.18] or KCl (E max =41.65±1.32%; pD 2 =3.55±0.1). Nω-nitro-L-arginine methyl ester (100 µM) significantly inhibited this effect, while it was not affected by 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (10 µM) and indomethacin (5 µM). In artery rings without endothelium, vasorelaxation induced by Sim was attenuated by 4-aminopyridine (100 µM), but was not affected by barium chloride dehydrate (10 µM), glibenclamide (10 µM) and traethylammonium chloride (1 mM). Moreover, Sim also inhibited the contraction induced by increasing external calcium in Ca 2+ -free medium with added KCl (60 mM). These results suggested that Sim induces relaxation of superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release and also through an endothelium-independent pathway, involving the opening of voltage-dependent K + channels and blockade of extracellular Ca 2+ influx.

show abstract

Section: Methodsmentioning

confidence: 99%

Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

Chen¹,

Zhang

Liu

et al. 2016

Biomedical Reports

View full text Add to dashboard Cite

show abstract

“…To determine the involvement of voltage-dependent Ca 2+ channels (VDCC), α 1 -adrenoceptors and 5-HT receptors in the relaxant effect of formononetin, concentration-response curves of KCl, CaCl 2 in Ca 2+ -free depolarized medium, phenylephrine and 5-HT in the presence of formononetin were constructed. Some mesenteric artery rings were incubated in a Ca 2+ -free Krebs solution to determine whether the relaxant effect of formononetin was due to its inhibition of intracellular Ca 2+ release or extracellular Ca 2+ influx [26,27] .…”

Section: Myograph Experimentsmentioning

confidence: 99%

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Sun

Cao

2011

Acta Pharmacol Sin

Self Cite

View full text Add to dashboard Cite

Aim: To investigate the mechanisms underlying the vasorelaxant effect of formononetin, an O-methylated isoflavone, in isolated arteries, and its antihypertensive activity in vivo. Methods: Arterial rings of superior mesenteric arteries, renal arteries, cerebral basilar arteries, coronary arteries and abdominal aortas were prepared from SD rats. Isometric tension of the arterial rings was recorded using a myograph system. Arterial pressure was measured using tail-cuff method in spontaneously hypertensive rats. Results: Formononetin (1-300 μmol/L) elicited relaxation in arteries of the five regions that were pre-contracted by KCl (60 mmol/L), U46619 (1 μmol/L) or phenylephrine (10 μmol/L). The formononetin-induced relaxation was reduced by removal of endothelium or by pretreatment with L-NAME (100 μmol/L). Under conditions of endothelium denudation, formononetin (10, 30, and 100 μmol/L) inhibited the contraction induced by KCl and that induced by CaCl 2 in Ca 2+ -free depolarized medium. In the absence of extracellular Ca 2+ , formononetin (10, 30, and 100 μmol/L) depressed the constriction caused by phenylephrine (10 μmol/L), but did not inhibit the tonic contraction in response to the addition of CaCl 2 (2 mmol/L). The contraction caused by caffeine (30 mmol/L) was not inhibited by formononetin (100 μmol/L). Formononetin (10 and 100 μmol/L) reduced the change rate of Ca 2+ -fluorescence intensity in response to KCl (50 mmol/L). In spontaneously hypertensive rats, formononetin (5, 10, and 20 mg/kg) slowly lowered the systolic, diastolic and mean arterial pressure. Conclusion: Formononetin causes vasodilatation via two pathways: (1) endothelium-independent pathway, probably due to inhibition of voltage-dependent Ca 2+ channels and intracellular Ca 2+ release; and (2) endothelium-dependent pathway by releasing NO. Both the pathways may contribute to its antihypertensive effect.

show abstract

“…1), a phthalide derivative, is the most abundant constituent in the herb (Li et al, 2002Yan et al, 2005). Vasodilatation, antiplatelet aggregation, antithrombotic, serotonergic activity, and antiproliferative properties of ligustilide have been well documented (Naito et al, 1995;Cao et al, 2006;Deng et al, 2006;Du et al, 2006;Lu et al, 2006;Chan et al, 2007). Hence, ligustilide is considered to be a key active ingredient in Chuanxiong.…”

mentioning

confidence: 99%

“…Nineteen compounds from L. chuanxiong have been reported to be pharmacologically active (Naito et al, 1995;Ko et al, 1997Ko et al, , 1998Ko et al, , 2002Matsumoto et al, 1998;Chong and Feng, 1999;Shih et al, 2002). In particular, phthalides are present in large quantities in Chuanxiong essential oil; these compounds have been shown to have in vitro and in vivo pharmacological activities (Naito et al, 1995;Ko et al, 1998Ko et al, , 2002Matsumoto et al, 1998;Chong and Feng, 1999;Cao et al, 2006;Chan et al, 2006Chan et al, , 2007Du et al, 2006;Lu et al, 2006). Ligustilide (Z-3-butylidene-4,5-dihydroisodenzofuranone) (Fig.…”

mentioning

confidence: 99%

Pharmacokinetics and Metabolism of Ligustilide, a Major Bioactive Component in Rhizoma Chuanxiong, in the Rat

Yan

Ko²,

Li³

et al. 2007

Drug Metab Dispos

115

View full text Add to dashboard Cite

ABSTRACT:Ligustilide is the most abundant bioactive ingredient in Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. The present study reported, for the first time, the pharmacokinetics of ligustilide, administered in its pure form and in an herbal extract, in rats. After i.v. administration of pure ligustilide, it was distributed extensively (V d , 3.76 ؎ 1.23 l/kg) and eliminated rapidly (t 1/2 , 0.31 ؎ 0.12 h). The i.v. clearance (CL) of ligustilide after Chuanxiong extract administration was significantly higher than that dosed in its pure form [CL, 20.35 ؎ 3.05 versus 9.14 ؎ 1.27 l/h/kg, p < 0.01; area under the curve (AUC), 0.79 ؎ 0.10 versus 1.81 ؎ 0.24 mg ⅐ h/l, p < 0.01], suggesting significant interaction between ligustilide and components present in the extract. Dose-dependent pharmacokinetics was observed after i.p. administration, and a significantly higher dose-normalized AUC (1.77 ؎ 0.23 mg ⅐ h/l) at 52 mg/kg was obtained than that at 26 mg/kg (0.93 ؎ 0.07 mg ⅐ h/l, p < 0.05). Oral bioavailability of ligustilide was low (2.6%), which was partly because of extensive first-pass metabolism in the liver. Seven metabolites of ligustilide were identified, and three of them were unequivocally characterized as butylidenephthalide, senkyunolide I, and senkyunolide H. These three compounds also occurred naturally in the herb and were reported to be bioactive.Rhizoma Chuanxiong [Ligusticum chuanxiong Hort. (Umbelliferae)], known as Chuanxiong in Chinese, a commonly used Chinese medicinal (CM) herb, has been used for treating cardiovascular diseases in China for centuries (State Pharmacopoeia Commission of P.R. China, 2005). In addition to raw herb preparations used in conventional CM practice, various Chuanxiong-based proprietary products containing Chuanxiong crude extract, especially Chuanxiong essential oil extract, are also used clinically. For instance, Quickacting Heart Saving Pill (Chinese name, Suxiao Jiuxin Wan), a product manufactured for sublingual delivery, contains Chuanxiong essential oil extract as the primary ingredient. In recent years, this product is one of the top five best-selling CM-based cardiovascular products in China (Sun et al., 2002;Li, 2005).In the past decades, the phytochemistry of Chuanxiong has been studied extensively. Nineteen compounds from L. chuanxiong have been reported to be pharmacologically active (Naito et al., 1995;Ko et al., 1997Ko et al., , 1998Ko et al., , 2002Matsumoto et al., 1998;Chong and Feng, 1999;Shih et al., 2002). In particular, phthalides are present in large quantities in Chuanxiong essential oil; these compounds have been shown to have in vitro and in vivo pharmacological activities (Naito et al., 1995;Ko et al., 1998Ko et al., , 2002Matsumoto et al., 1998;Chong and Feng, 1999;Cao et al., 2006;Chan et al., 2006Chan et al., , 2007Du et al., 2006;Lu et al., 2006). Ligustilide (Z-3-butylidene-4,5-dihydroisodenzofuranone) (Fig. 1), a phthalide derivative, is the most abundant constituent in the herb (...

show abstract

Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release

Cited by 84 publications

References 14 publications

Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

Mechanisms of simvastatin-induced vasodilatation of rat superior mesenteric arteries

Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms

Pharmacokinetics and Metabolism of Ligustilide, a Major Bioactive Component in Rhizoma Chuanxiong, in the Rat

Contact Info

Product

Resources

About