Endothelium-Independent Vasorelaxation by Ligusticum wallichii in Isolated Rat Aorta: Comparison of a Butanolic Fraction and Tetramethylpyrazine, the Main Active Component of Ligusticum wallichii

Abstract

Ligusticum wallichii FRANCHAT (or Ligusticum chuanxiong hort; L. wallichii), a member of the Umbelliferaceae family, is a Chinese medicinal herb that is a common constituent in polypharmaceutical herbal drugs. It has been widely used in Asian countries to increase coronary blood flow and systemic circulation, and to relieve stasis. 1,2) Previous studies have indicated that L. wallichii improves blood fluidity 3) and inhibits endothelial cell damage 4) and vascular smooth muscle cell proliferation. 5)We demonstrated that an extract of L. wallichii showed endothelium-dependent acute relaxation in isolated rat thoracic aorta.6) The effect of L. wallichii was due to endothelial nitric oxide (NO). However, the tetramethylpyrazine (TMP)-induced vasorelaxant effect was not related to endothelial NO. TMP was isolated as a biologically active component from L. wallichii. Since 1970, TMP has been used in China for the treatment of patients with angina pectoris and cerebral ischemic syndromes. [7][8][9] Earlier pharmacological studies demonstrated that aortic vasorelaxation induced by TMP involved the opening of ATP-sensitive K ϩ channels and/or small-conductance Ca 2ϩ -activated K ϩ channels. [10][11][12] Endothelium-derived relaxing factor (EDRF) and the membrane potential are major components in modulating vascular tone.13) After EDRF, the most important molecule is probably NO,14,15) and K ϩ channels play an important role in the regulation of membrane potential.16) Five distinct types of K ϩ channel have been documented in arterial smooth muscle: voltage-dependent K ϩ (K V ) channels, large-conductance Ca 2ϩ -activated K ϩ (LK Ca ) channels, small-conductance Ca 2ϩ -activated K ϩ (SK Ca ) channels, inward rectifier K ϩ (K IR ) channels, and ATP-sensitive K ϩ (K ATP ) channels. 16) Additionally, changes in K ϩ channel activity to produce a subsequent alteration in the activity of calcium channels may result in vasorelaxation.17) Thus, the present study was performed to separate the active fraction, to examine the active fractioninduced changes in membrane potential, the possible underlying mechanisms, and to perform comparisons with TMP using isolated endothelium-denuded rat aortic rings. MATERIALS AND METHODS Extraction and FractionationDried, sliced L. wallichii was obtained from a local market and ground with a commercial food mixer. The resulting powder was extracted under reflux with absolute ethanol for 1 h. The extract was evaporated under reduced pressure at low temperature (37-40°C) and lyophilized (LwEx). Extracts for all of the experiments were prepared from four batches of L. wallichii to assess variation in individual extracts. LwEx was fractionated successively with water and n-butanol, and each phase was concentrated and lyophilized into water-soluble (LwDw) and butanol-soluble (LwBt) fractions. The solid was stored at Ϫ20°C until use. LwEx and LwBt were dissolved in 30% ethanol and LwDw was dissolved in water to give final concentrations of 0.3 to 3.0 mg/ml in the bath. Voucher specimen nos. Lw-001 (LwE...

Protective effect of ligustrazine against myocardial ischaemia reperfusion in rats: The role of endothelial nitric oxide synthase

“…As a traditional Chinese medicine used in many ischaemia disorders, TMP has been reported to increase left ventricular systolic pressure and coronary blood flow, relax vessels, 19 relieve stasis, and inhibit endothelial cell damage and vascular smooth muscle cell proliferation 20 . In the present study, the effect of TMP on IR injury in rats was investigated by evaluating myocardial infarct size, tissue oxidant parameters and myocardial apoptosis.…”

Study on the Absorbed Fingerprint-Efficacy of Yuanhu Zhitong Tablet Based on Chemical Analysis, Vasorelaxation Evaluation and Data Mining

“…In addition, intestinally absorbed YZT solutions of 6 cumulative doses were investigated and 1600 mL of the intestinally absorbed solution was selected as the maximum dose for additional experiments. Ligustrazine is an active constituent of Ligusticum chuanxiong Hort (Umbelliferae) and it has been known as a vasorelaxation compound [35], so ligustrazine was chose as a positive control in the pharmacological tests, which had exhibited very good vasorelaxation (74.96±11.10) in this study.…”

Synergistic vasorelaxant and antihypertensive effects of Ligusticum wallichii and Angelica gigas

“…Changes in potassium channel activity to produce a subsequent alteration in the calcium channels may also result in vasorelaxation (Standen and Quayle, 1998). The endothelium-independent relaxation caused by MxBt11 was inhibited calcium influx in smooth muscle by opening of inward rectifier potassium channel, though individual AgBt and LwBt did not affect by inward rectifier, voltage dependent, and large conductance Ca 2+ -activated potassium-channel inhibitors, respectively (Rhyu et al, 2005;Kim et al, 2010), indicating the reinforcement of Ligusticum wallichii and Angelica gigas.…”

“…Values in a same time not followed by the same alphabetical letter are significantly different (P < 0.05, n = 4-6). The results of LwDw and AgDw were reported inRhyu et al (2005) andKim et al (2010), respectively.…”