Lingusticum Chuanxiong
Selected from ~150 articles
Lee TF. Lin YL. Huang YT. Studies on antiproliferative effects of phthalides from Ligusticum chuanxiong in hepatic stellate cells. Planta Medica. 73(6):527-34, 2007. Suppression of hepatic stellate cell (HSC) growth and activation, and induction of apoptosis, have been proposed as therapeutic strategies for the treatment and prevention of liver fibrosis. Our previous study showed that the Chinese herb Ligusticum chuanxiong (LC) inhibits platelet-derived growth factor (PDGF-BB)-induced HSC proliferation. The present study was designed to investigate the active principles and their action mechanisms. With a bioactivity-directed fractionation approach, DNA synthesis (bromodeoxyuridine (BrdU) incorporation), cell cycle related proteins and apoptosis markers were determined to evaluate the inhibitory effects of active principles of LC. Two phthalides, Z,Z'-6,8',7,3'-diligustilide (1) and levistolide A (2), from LC significantly abrogated PDGF-BB-induced proliferation in both rat and human HSC lines. These inhibitory effects of compounds 1 and 2 were associated with reduction of alpha-smooth muscle actin and collagen expressions. The cell cycle promoting proteins, cyclins D1, D2, E, A and B1, were downregulated while the inhibitory proteins p21 and 27 were up-regulated. JNK phosphorylation was up-regulated by compounds 1 and 2. In HSC-T6, the two compounds induced apoptosis through the activation of caspases 9 and 3, increase in cytosolic cytochrome c release, and downregulation of Bcl-2 and Akt phosphorylation. Moreover, neither phthalides caused direct cytotoxicity to either HSCs or rat primary hepatocytes under experimental concentrations. These results indicate that two phthalides from LC inhibited PDGF-BB-activated HSC proliferation possibly through cell cycle inhibition and apoptosis mechanisms. They might be potential anti-fibrotic drugs for the treatment and prevention of hepatic fibrosis.
Chan SS. Cheng TY. Lin G. Relaxation effects of ligustilide and senkyunolide A, two main constituents of Ligusticum chuanxiong, in rat isolated aorta. Journal of Ethnopharmacology. 111(3):677-80, 2007. Ligusticum chuanxiong Hort. (Umbelliferae) is a widely prescribed traditional Chinese medicinal herb for cardiovascular diseases in China. However, the cardiovascular actions of ligustilide and senkyunolide A, two of the most abundant Ligusticum chuanxiong constituents, have yet to be examined. The objective of the present study was to investigate the vasorelaxation effects of ligustilide and senkyunolide A and their underlying mechanisms in rat isolated aorta. Both constituents had similar relaxation potencies against contractions to 9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F(2alpha), phenylephrine, 5-hydroxytryptamine and KCl. Their vasorelaxation effects were not affected by endothelium removal, the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the non-selective K+ channel blocker tetraethylammonium. This is the first report to demonstrate the vasorelaxation activities of ligustilide and senkyunolide A in contractions to various contractile agents in rat isolated aorta. The underlying mechanisms await further investigations.
Chan SS. Choi AO. Jones RL. Lin G. Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta. European Journal of Pharmacology. 537(1-3):111-7, 2006. Butylidenephthalide (BDPH) is one of the most potent vasorelaxants isolated from Ligusticum chuanxiong Hort. The objective of the current study is to investigate the underlying vasorelaxation mechanisms in rat aorta. In 9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F(2alpha) (U46619) precontracted preparations, endothelium removal, the nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) partially inhibited the BDPH relaxation response to a similar extent. The cyclooxygenase inhibitor indomethacin, beta-adrenoceptor antagonist propranolol, adenylate cyclase inhibitors 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and 2',5'-dideoxyadenosine, and K(+) channel blocker tetraethylammonium had no effect. BDPH produced full relaxation against contractions induced by KCl and U46619 in the presence of the l-type voltage-operated Ca(2+) channel (Ca(v) 1.2) blocker nifedipine. In a receptor-operated Ca(2+) channel protocol where contraction was mediated by Ca(2+) re-addition in the presence of U46619 and nifedipine, BDPH produced relaxation. In the absence of extracellular Ca(2+), BDPH inhibited contractions induced by phorbol-12,13-dibutyrate and U46619. Our results suggest that BDPH-mediated vasorelaxation comprises both endothelium-dependent (NO) and independent components. It is suggested that BDPH acting through an inhibitory mechanism downstream to l-type voltage-operated and prostanoid TP receptor-operated Ca(2+) channels operating late in the contractile pathway.
Liang MJ. He LC. Yang GD. Screening, analysis and in vitro vasodilatation of effective components from Ligusticum Chuanxiong. Life Sciences. 78(2):128-33, 2005. Effective components, ligustilide and butylidenephthalide, from Ligusticum Chuanxiong (Ligusticum wallichii Franchat, Umbelliferae) were screened and identified by using a cell membrane chromatography (CMC) and a gas chromatography/mass spectrometry (GC/MS). The components showed the effects of inhibiting vasoconstriction in vitro on rat abdominal aorta segments. The screening procedure was performed in a rat artery CMC column (50 mm x 2.0 mm I.D.) with a sodium phosphate buffer (pH 7.4) as mobile phase at 37 degrees C. The identification was accomplished by a DB-5MS 30 m capillary column (0.25 mm I.D., 0.25 microm film thickness) with helium as carrier gas operating under program control temperature and electron impact ionization mass spectrometer in a scan mode. Results demonstrated that ligustilide and butylidenephthalide can act on rat artery cell membrane similar to verapamil in CMC system. They significantly inhibited the vasoconstrictions induced by norepinephrine bitartrate (NE) and calcium chloride (CaCl2). The relaxing effect of ligustilide on the NE- and CaCl2-induced constrictions is more potent than that of butylidenephthalide. Ligustilide and butylidenephthalide seem to be the two main effective components of Ligusticum Chuanxiong as a traditional Chinese medicine for treating blood vessel diseases.
Liu L. Ning ZQ. Shan S. Zhang K. Deng T. Lu XP. Cheng YY. Phthalide Lactones from Ligusticum chuanxiong inhibit lipopolysaccharide-induced TNF-alpha production and TNF-alpha-mediated NF-kappaB Activation. Planta Medica. 71(9):808-13, 2005. The dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae) is a traditional Chinese medicine (TCM) herb for the prevention and treatment of inflammatory and cardiovascular diseases. However, the role of phthalide lactones from Ligusticum chuanxiong in the therapeutic actions is not yet fully understood. In the present study, two phthalide lactones from the herb, Z-ligustilide and senkyunolide A, were identified and characterized as inhibitors of lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes. The results of gene expression studies showed that the observed TNF-alpha suppression was related to their inhibitory activity on TNF-alpha mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-alpha-mediated nuclear factor-kappaB (NF-kappaB) activation in reporter gene assays. Taken together, the results suggest that Z-ligustilide and senkyunolide A may have potential applications in the treatment of inflammation and related diseases based on their inhibitory activity on TNF-alpha production and TNF-alpha bioactivity. New insights into the therapeutic basis of the TCM herb, Ligusticum chuanxiong, are presented.
Lu ZM. Yu YR. Tang H. Zhang XX. The protective effects of Radix Astragali and Rhizoma Ligustici chuanxiong on endothelial dysfunction in type 2 diabetic patients with microalbuminuria. Sichuan da Xue Xue Bao. Yi Xue Ban/Journal of Sichuan University. Medical Science Edition. 36(4):529-32, 2005. OBJECTIVE: To evaluate the effects of traditional Chinese complex prescription of Radix Astragali and Rhizoma Ligustici Chuanxiong on urinary albumin excretion (UAE) and vascular endothelial dysfunction in type 2 diabetic patients with microalbuminuria. METHODS: Twenty-one type 2 diabetic patients with microalbuminuria were involved in this before-after study by individual informed consent. Each of the eligible subjects was given the decoction of Radix Astragali and Rhizoma Ligustici Chuanxiong per os 150 ml q.d. for six months. The following examinations were performed at baseline and after treatment: (1) high-resolution ultrasonography to measure the diameter changes of brachial artery in response to reactive hyperemia (endothelium-dependent) and on administration of glyceryl trinitrate (endothelium-independent); (2) high resolution ultrasonography to measure combined intima-media thickness (IMT) of common carotid arteries (CCA); (3) fasting plasma plasminogen activator inhibitor type 1 (PAI-1) activity, C reactive protein (CRP) and malonic aldehyde(MDA) concentration. RESULTS: The patients had impaired endothelial dependent vasodilation (EDV), elevated plasma PAI-1 activity and increased CRP and MDA concentration at baseline. After six months treatment with Radix Astragali and Rhizoma Ligustici Chuanxiong, their urinary albumin-to- creatinine ratio decreased from (86.5 +/- 53.9) microg/mg to (55.05 +/- 51.67) microg/mg (P=0.002). The EDV was improved at the end of the treatment (baseline: 7.49 +/- 2.98%, after treatment: 12.73 +/- 5.36%, P=0.001). Meanwhile, the activity of PAI-1 and the levels of MDA and CRP were significantly decreased CPAI-1: (83.49 +/- 5.11) X 10(-2) AU/ml vs. (79.7 +/- 7.8) x 10(-2) AU/ml, P=0.015; MDA: (3.20 +/- 1.13) nmol/L vs. (2.09 +/- 0.71) nmol/L, P=0.000; CRP: (7.04 +/- 2.64) mg/ L vs. (1.58 +/- 0.69) mg/L, P=0.000]. But no significant changes of the CCA IMT and endothelial independent vasodilation (EIV) were observed. Partial correlated analysis showed that MDA concentration was negatively correlated with EDV (r=-0.3736, P = 0.018). Correlated analysis also showed that CRP was negatively correlated with EDV (r=-0.348, P=0.028). CONCLUSION: Radix Astragali and Rhizoma Ligustici Chuanxiong compound medication may decrease urinary albumin excretion and improve endothelial dysfunction in type 2 diabetic patients with microalbuminuria. The mechanism may relate with the therapeutic effects of Radix Astragali and Rhizoma Ligustici Chuanxiong on anti-inflammation, anti-oxidation and alleviation of the hypo-fibrinolytic/pro-thrombotic state.
Hou YZ. Zhao GR. Yuan YJ. Zhu GG. Hiltunen R. Inhibition of rat vascular smooth muscle cell proliferation by extract of Ligusticum chuanxiong and Angelica sinensis. Journal of Ethnopharmacology. 100(1-2):140-4, 2005. Ligusticum chuanxiong (LC) and Angelica sinensis (AS) have been widely used as traditional Chinese medicine to treat some pathological settings such as atherosclerosis and hypertension. The aim of this paper is to determine the effects of the extract of LC and AS (ELCAS) on serum-induced vascular smooth muscle cell (VSMC) proliferation, cell cycle and nitric oxide production. The results show that ELCAS significantly inhibited proliferation and protein synthesis of VSMC in a dose and time dependent manner. The cell population assessed by flow cytometry in the G(0)/G(1) phase increased 74% versus 79.8%, concomitant with a decrease in the S phase, 7.4% versus 4.2%, for control versus ELCAS (300 microg/ml). On the other hand, ELCAS significantly increased nitric oxide production of VSMC. The data suggest that ELCAS markedly inhibited VSMC proliferation by arresting G(1) to S progression, which may be associated with nitric oxide production.
Wen C. Xu H. Huang QF. Effect of drugs for promoting blood circulation on blood lipids and inflammatory reaction of atherosclerotic plaques in ApoE gene deficiency mice. Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi/Chinese Journal of Integrated Traditional & Western Medicine/Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. 25(4):345-9, 2005. OBJECTIVE: To observe the effect of six common Chinese medicinal herbs for promoting blood circulation, including Radix Paeoniae rubra (I), Radix Salviae miltiorrhizae (II), Rhizoma Chuanxiong (III), Radix Notoginseng (IV), Semen Persicae (V) and wine steamed Radix et Rhizoma Rhei (VI), on blood lipids and inflammatory reaction of atherosclerotic plaques in ApoE gene deficiency mice. METHODS: Ninety mice, 6 - 8 weeks old, were divided into 8 groups, the model group, the control group (treated with simvastatin) and the six treated groups treated with the above-mentioned 6 Chinese medicinal herbs respectively. All the mice were fed with the diet of western kind for 13 weeks until the mature atherosclerotic plaques formed in them. Then they were treated with respective drugs for another 13 weeks except those in the model group. All the mice were sacrificed at the end of experiment, their blood was collected for lipids determination, heart and aorta were taken out for determining the level of CD68 in root of aorta, as well as the expressions of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-a (TNF-a) by immunohistochemistry staining. RESULTS: All the 6 Chinese herbs showed regulatory action on blood lipids. The positive expression of CD68 in the model group displayed the highest activity. As compared with the model group, the CD68 positive expressed cells in the control group and the groups treated with Chinese herbs II, III, and IV were lesser (P < 0.05), and the expression of inflammatory factors (MCP-1 and TNF-alpha) in atherosclerotic plaques was significantly lower in the control group and the group treated with Chinese herb VI (P < 0.05). CONCLUSION: Chinese medicinal herbs tested in this study can interfere the maturing progress of atherosclerotic plaques and stabilize the plaques in ApoE deficiency mice, the mechanisms may relate to its actions in regulating lipids metabolism and inhibiting inflammatory reaction. Different Chinese medicinal herbs for activating blood circulation of conventional dosage might show difference in potency and acting links.
Tian JW. Fu FH. Jiang WL. Wang CY. Sun F. Zhang TP. Protective effect of ligusticum chuanxiong phthalides on focai cerebral ischemia in rats and its related mechanism of action. Zhongguo Zhong Yao Za Zhi/Zhongguo Zhongyao Zazhi/China Journal of Chinese Materia Medica. 30(6):466-8, 2005. OBJECTIVE: To study the protective effect of ligusticum chuanxiong phthalides on cerebral ischemia in rats and its related mechanism of action. METHOD: Middle cerebral artery occlusion (MCAO) model, thrombosis formation, platelet aggregation and hemorrheological parameters were measured to evaluate the protective effect of ligusticum chuanxiong phthalides. RESULT: Ligusticum chuanxiong phthalides could markedly decrease the infarct size and behavior deficits score, inhibit the thrombus formation and platelet aggregation, ameliorate hemorrheological parameters with a dose-dependent manner in rats.CONCLUSION: Ligusticum chuanxiong phthalides has protective effects on focal cerebral ischemia in rats, and its mechanism may be relevant to its inhibition of platelet-dependent thrombosis and amelioration of hemorrheological parameters.
Hou YZ. Zhao GR. Yang J. Yuan YJ. Zhu GG. Hiltunen R. Protective effect of Ligusticum chuanxiong and Angelica sinensis on endothelial cell damage induced by hydrogen peroxide. Life Sciences. 75(14):1775-86, 2004. Ligusticum chuanxiong and Angelica sinensis have been widely used in traditional Chinese medicine to treat some pathological settings such as atherosclerosis and hypertension. We determined the protective effect of the extract of Ligusticum chuanxiong and Angelica sinensis (ELCAS) on human umbilical vein endothelial cells (ECV304) damage induced by hydrogen peroxide. ECV304 cells were pre-treated with ELCAS and exposed to 5 mM hydrogen peroxide. The results show that ELCAS dose- and time-dependently protected ECV304 cells against hydrogen peroxide damage and suppressed the production of reactive oxygen species (ROS). The decrement of ROS may be associated with increased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Western blot analysis revealed that ELCAS significantly increased the phosphorylation of ERK and promoted eNOS expression. These observations indicate that ELCAS protected ECV304 cells against hydrogen peroxide damage by enhancing the antioxidative ability, activating ERK and eNOS signaling pathway. Our data also provide new evidence of Ligusticum chuanxiong and Angelica sinensis in preventing both cardiovascular and cerebrovascular diseases.
Wang Y, Tong J, Tang R, Dong H, Xu J. Inhibitory Effects of Ligustrazine, a Modulator of Thromboxane-Prostacycline-Nitric Oxide Balance, on Renal Injury in Rats with Passive Heyman Nephritis. Nephron Physiol 2004;98:80-88 Shih YH. Wu SL. Chiou WF. Ku HH. Ko TL. Fu YS. Protective effects of tetramethylpyrazine on kainate-induced excitotoxicity in hippocampal culture. Neuroreport. 13(4):515-9, 2002. Tetramethylpyrazine (TMP) is the major component extracted from the Chinese herb, Chuanxiong. This study focuses on the protective effect of tetramethylpyrazine in kainate-induced excitotoxicity in rat hippocampus. Primary neuronal cultures raised from cells isolated from the hippocampi of 7-day old rats were treated with kainate (75-450 microM) for 12, 24, and 48 h. Our results revealed that kainate induced neuronal damage in a dose- and time-dependent manner, reaching maximal damage at 150 microM and 24 h and persisted for higher doses and 48 h. In addition, 1 h of kainate (150 microM) treatment led to significant generation of free radicals and reduction of mitochondrial membrane potential (MMP) which persisted for > or = 4 h on continued exposure. Ten minutes pretreatment with 1 or 5 microM tetramethylpyrazine dose dependently and significantly attenuated the kainate-induced damage. Taken together, the results suggest that multiple mechanisms including protection of mitochondria, decrease in free radical generation and scavenging of free radicals might be involved in TMP's protection against kainate induced cell toxicity.
Li M. Handa S. Ikeda Y. Goto S. Specific inhibiting characteristics of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine 'Chuanxiong,' on platelet thrombus formation under high shear rates. Thrombosis Research. 104(1):15-28, 2001. We have investigated the effects of tetramethylpyrazine, one of the active ingredients of the Chinese herbal medicine Chuanxiong, on platelet thrombus formation under flow conditions. We demonstrate herein that tetramethylpyrazine inhibits shear-induced platelet aggregation under relatively high shear rate of 10,800 s(-1) with modest inhibition of those occurring under relatively low shear rate of 1200 s(-1) by using optically modified cone-plate viscometer. We also demonstrate that platelet activation induced by shearing in the absence of exogenous platelet-activating agents such as ADP as evidenced by P-selectin surface expression and microparticle release detected by quantitative flow cytometry was also inhibited by tetramethylpyrazine. Moreover, we also demonstrate platelet thrombus formation on the collagen and von Willebrand factor (vWF) surface at high shear rates without significant influences on those occurring under relatively low shear rates. Because platelet thrombus formation occurring under high shear rates is known to be mediated by the vWF interaction with platelet receptor proteins GP Ibalpha and GP IIb/IIIa, we speculated that tetramethylpyrazine exerts antiplatelet effects by inhibiting the vWF-mediated process of platelet thrombus formation. Our findings, indicating the unique antiplatelet characteristics of tetramethylpyrazine, selectively inhibiting the platelet thrombus formation under high shear rates, provide good reasons for developing chemical analogs having biological functions similar to or more potent than those of tetramethylpyrazine as antiplatelet agents having unique biological functions.
Ni JW. Matsumoto K. Watanabe H. Tetramethylpyrazine improves spatial cognitive impairment induced by permanent occlusion of bilateral common carotid arteries or scopolamine in rats. Japanese Journal of Pharmacology. 67(2):137-41, 1995. Effects of tetramethylpyrazine (TMP), a major constituent of Ligusticum chuanxiong, on spatial cognitive impairment induced by permanent occlusion of bilateral common carotid arteries (2VO) and scopolamine were investigated using 8-arm radial maze performance in rats. Permanent 2VO produced a severe learning deficit in non-pretrained rats. Daily administration of TMP (3-10 mg/kg, i.p.) from the 3rd day after permanent 2VO significantly improved the learning deficit. TMP did not influence the impairment of the retention task in the pretrained permanent 2VO rats, but it tended to reduce the number of errors elevated by 3-min delay interposition in these rats. In the scopolamine model, scopolamine (0.3 mg/kg, i.p.) significantly decreased the initial correct response and increased the number of errors. Single administration of TMP (1-3 mg/kg, i.p.) dose-dependently reversed the scopolamine-induced impairment of the maze performance. These results suggest that TMP has therapeutic potential for the treatment of dementia caused by cholinergic dysfunction and/or decrease of cerebral blood flow.
