Herbal pharmacology and Drug interaction of the Herbs that Remove Blood Stasis

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‎ts‏ طبایع 

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Herbal pharmacology and Drug interaction of the Herbs that Remove Blood Stasis For 2010 Acupuncture Continue Education Dr. Baisong Zhong Ph.D, L.Ac, M.D(China) WWW: Easternbalancetcm.com E-mail: Painandacupncture@yahoo.com 

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pharmacology and Drug Interaction of the Herbs that Remove Blood Stasis 1. Actions of the herbs a3) (1) Improve the microcirculation Blood stasis is the most common pathogenesis of disorders of microcirculation, such as coronary heart disease, cerebral diseases. This group herbs can improve the fluid, 

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(2)Improve hematology and against coagulation Blood stasis is related to thrombus formation due to “thickness, stickiness, coagulation and accumulation” of blood in circulation. Most of the herbs that remove blood stasis have excellent function of improving the tendency of “thickness, stickiness, coagulation and accumulation” of blood in circulation. They have inhibitory influence on thrombus formation, and are used in treatment of angina, embolism and stroke. The herbs include Dan Shen(Radix Salviae Mitiorrhizae), Chuan Xiong(Rhizoma Ligustici Chuanxiong), Hong Hua(Flos Carthami). 

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(3)Dilate blood vessel and increase blood perfusion to small vessels. The herbs that dilate coronary arteries include Shui Zhi(Hirudo), E Zhu(Rhizoma Curcumae), Tao Ren(Semen Persicae), Chuan Xiong(Rhizoma Ligustici 5 (4)Antineoplastic: Some of the herbs can inhibit the growth of cancer cells in vitro. The examples are San Leng(Rhizoma Sparganii), E Zhu(Rhizoma Curcumae), Sanqi (Panax notoginseng). 

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(5)Lower cholesterol The herbs are Sanqi (Panax notoginseng), Dan Shen (Radix Salviae Mitiorrhizae), Pu Huang(Pollen Typhae). 2. Potential Herb-drug Interactions «) (1)Antiplatelets and anticoagulants: The group herbs may enhance the actions of antiplatelets and anticoagulants medications, and prolong bleeding, such as warfarin, heparin, lepirudin, salicylate . 

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(2)Antihypertensives: Some of the group of herbs may dilate the blood vessels, which may potentiate the effect of antihypertensiv medications. ‎cate}‏ اذا ‎1.Qian Xin-zhong. Chinese Materia Medica. People’s Medical Publishing House. 2007.Beijing ‎2. Shen Yin-jun. Chinese Herbal Pharmacology. People’s Medical Publishing House. 2000.Beijing ‎3. John Chen, Tina T Chen. Chinese Medical Herbology and Pharmacology. Art of Medicine Press, Inc. 2009. City of ‏ل‎ OF. 

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Dan Shen(Radix ‏اكت‎ 

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News 0 BEIJING, Aug. 7 (Xinhua) -- A China-made pill to treat cardiovascular conditions has been tested safe and effective by the U.S. Food and Drug Administration (FDA), and, hopefully, will be marketed in the U.S. as early as 2013, a pharmaceutical company said here Saturday. http://news.xinhuanet.com/english2010/china/2010-08/07/c_13434173.htm) FDA reports: Dan Shen and Ge Gen are in clinical trial-Phase II: Cardiovascular-Protective Effects of Herbal Medicine panshen-Gegen(http:/clinicaltrials.gov/ct2/show/NCT01033630? ۱3 ee) 

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Dan sher Dan Shen is the root and rhizome of salvia miltiorrhiza Bge., family Labiatae. Properties: Bitter and slightly cold Channels entered: Heart, pericardium, and liver 1. Actions and indications « Actions and indications in TCM (1) Invigorates the blood and breaks up blood stasis: It is used for blood stasis disorders in lower abdomen such as dysmenorrhea, amenorrhea, masses. It is also used for Chest peat 

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صعطة (2)Clears heat and smoothes irritability It is used for restlessness, irritability, palpitation. (3)Cools blood and expels pus It is used for heat in the blood level, skin sores due to toxic heat. 

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Dan sher 2. Chemical Ingredients in Danshene34) Dan Shen has more than 50 compounds: Tanshinonel, TanshinonellA, Tanshinone IIB, Cryptotanshinone, Cryptotanshinone, Danshensu(Salviania acid A), Isotanshinonel, Isotanshinonell, Isocryptotanshinone, Tanshinoll, Tanshinolll. Methyl tanshinonate, hydroxytanshinone IIB , Vitamine E. 

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Dan shen 3.Pharmacokinetics., = Major components absorbed rapidly after oral administration = Metabolized extensively by liver = Excreted from stool and urine, =™ Some components have low short half life, low bioavailability, because of extensive metabolism 

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4. Actions and indications iPT1EHsal pharmacology Danshensuo7,2,9 Dilates coronary arteries, inhibits platelet aggregation, improves microcirculation, and protects the myocardium from reperfusion injury of the ischemic heart. Mechanisms: - prevent intracellular calcium increase - remove oxygen free radicals - Inhibit myocardial cell apoptosis - protect the endothelial cells against homocysteinemia (risk factor for cardiovascular diseases and atherosclerosis) 

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Dan sher Salvianolic Acid Buo, 11) Protect the brain from ischemia-reperfusion ۱۱۱۱۸ Mechanisms: -Inhibit platelet aggregation and oxidative modification of lowdensity lipoprotein(LDL), leading to the prevention of the uptake of LDLe2:13). -Inhibit erythrocyte hemolysis and lipid peroxide productionas -Inhibit DNA synthesis of noncardiomyocytes and inhibit stress-activated protein kinase activity, leading to protection of ischemia- reperfusion injury as) 

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Tanshinone ITA Dan Reduce myocardial infarct sizeas) ‏اتب‎ -Inhibit LDL oxidation and angiotensin II activity, resulting in attenuation of cardiac cell Boni oXcvmn oy ov enya The other actions: = Prevent cancer metastasisi7 Tanshinone II-A significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of colon carcinoma cells by reducing levels of urokinase plasminogen activator (uPA) and matrix 1 (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone II-A was also shown to suppress the nuclear factor-kappaB (NF-kappaB) signal. 

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Protect the liver injuryas) Dan shen Clinic researches: 1. Angina Pectoris -Danshen products were found to be better than isosorbide dinitrate(ISDN) for long term use -None of the Danshen products was found to be superior in efficiency to nitroglycerin, fewer side effects such as headache were found in Danshen group compared to that in the nitroglycerin groupcs). -Danshen dripping pill was found to achieve a higher rate of effectiveness in treating patients with angina pectoris in comparison to the Danshen Tablet. -Fufang Danshen Spray and injection were similar or better efficacy when compared to ISDNeo) 

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Dan shen -The improvement of exercise ECG from the Fufang Danshen Dripping Pill was found to be significantly better than ISDN. -The sublingual Fufang Danshen Dripping Pill is at least as effective as sublingual ISDN and comparable to sublingual nitroglycerine» 2. Hyperlipidemiac2) -Danshen products can reduce the level of cholesterol, triglyceride, and LDL, and raised the level of HDL. 

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Dan shen 3. Acute Ischemic Strokee:» -Improve the short-term effect of acute stroke patients -conducive to the recovery of patients with traumatic intracranial hematoma (TICH) -improves the microcirculation of femoral head, which is beneficial to repair and reconstruction of femoral head. 

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Dan shen Side effects. = No major side effects Patients who are taking Fufang Danshen Dripping Pill may felt thirsty(3/100), dizziness, drowsiness, abdominal discomfort(2/34), decrease appetite and itching. = LD50 of water soluble extract was almost 4000 times higher in mice than the clinical human oral dosage. 

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HERB-DRUG INTERACTION Dan shen 1. The anticoagulant response to warfarin could be exaggerated when coadministered with Danshen «27 2. Salicylate in therapeutic concentration was reported to be significantly decrease free Danshen concentration as measured by free-digoxin-like activity.s, DOSAGES: Ble Borers PWS =r eas Este 3 بعسة طعةة للقنةوصتاطبى عه ترللمده كللزم 10 :لز ‎ever lotto‏ .2 0 0 ‏ا‎ ms cmen ence Recs 

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1385 زر 8 

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Dan shen 1.Qian Xin-zhong. Chinese Materia Medica. People’s Medical Publishing House. 2007.Beijing 2. Zhou L , Zuo Z , Chow MS . Danshen: an overview of its 9 ‏ا‎ J eee steal and clinical use . J Clin Pharmacol . 2005;45(12):1345-1359. 3 andes , Morris-Natschke SL _, Lee KH . New developments in the chemistry and biology of the bioactive constituents of Tanshen . Méd Res Rev . 2007;27(1):133-148. 4. Jiang RW, Lau KM, Hon PM , Mak TC , Woo KS, Fung KP . Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza . Curr Med Chem . 2005;12(2):237-246. 5. Ye G, Wang CS, Li YY, Ren H, Guo XM. Simultaneous determinationand pharmacokinetic studies on (3,4- ery arent Puen ache acid and protocatechuic aldehyde in rat serum after oral administration of Radix Salvia miltiorrhiza extract. J Chromatogr Sci. 2003;41:327-330 6.Dong ZT, Jiang WD, Effect of Danshen of isolated swine 60101181 aed ‏بت‎ preparation. Yaoxue Xuebao. 1982:17:226-2( ۷ 4 ‏هک‎ SC, Zhao FD, et al. Anticoagulant Studies of Danshen. Zhongxiyi Jiehe Zazhi.1983;3:297-299 

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ال ةا 8. Dong C, Wang Y, Zhu YZ. Asymmetric synthesis and biological ‏وتسعطء 15 لمتفجوءه رمس سه عه دعقم 3ع تاكمء طكمة2 01 صمته لمرو‎ drug candidates. Bioorg Med Chem. 2009 May 1;17(9):3499-507. 9.Wu L, Qiao H, Li Y, Li L. Protective roles of puerarin and ۱ Ra CER Gn ann aL AUS Phytomedicine. 2007 Oct;14(10):652-8. Epub 2007 Sep 17. 10. Chen YH , Du GH, Zhang JT. Salvianolic acid B protects Brain against injuries caused by ischemia-reperfusion in rats. ZhongGuo inyao Zazhi. 2000:21:463-466. 11. He HB, Yang XZ, Shi MQ, et al. Comparison of cardioprotective ‏از‎ ee ece ECR RaR ee noe infarction in rats. Pharmacol Rep. 2008 May-Jun;60(3):369-81. 12. Han JY, Fan JY, Horie Y, et al. Ameliorating effects of compounds derived from Salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion, Pharmacol Ther. 2008 Feb:117(2):380-95. SRBC Ten VIGS Ce MONA Chen Ot ama cemaa leone etc pico ۱ ‏مه 10 لوماط لمسطعممه لمصمتومء يده ممعنط صم لتم‎ platelet aggregation in rats. Phytomedicine. 2002 Jul;9(5):405-9. ۶۳۱ pacMa mcr sr orcntoCmentl tits ore ‏ةذكق1امء درط لمتنهنهمه مهم ممتاما‌نره حتمامعمه نا «اتعومه‎ endothelium-denuded hypercholesterolaemic rabbits. J Sci Food ۸020, 2010 568 ۰ 15.Quyang XS, Takahashi K , Komatsu K, et al. Protective effects of Salvia miltiorrhiza on angiotension I-indued hypertrophic Foo oe Sa Coste Me Wl eee Ion UB aT nano VL ee 

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Dan shen ‎Mec TeeS belo Com OEM Ce letUcm em Ey‏ ا ا ل ‎Mine Re muri Retc teenie et arora Greta rete es‏ | ‎Eee‏ ا نا ‎| Roam Cena ENT ee le Maeno and metastasis of human colon carcinoma cells. Acta Pharmacol Sin. ‎2009; 30:1537-1542. ‎18. Chor SY, Hui AY, To KF, et al. Anti-proliferative and pro-apoptotic effects of 0 oti nen neta ieteo eae epee Ps) ‎19. Wang YY, Wang H. comparison of dissolving compound Salvia miltiorrhiza in mouth and dissolving nitroglycerin in mouth to treat angina pectoris. Henan Zhigong Yixueyuan Xuebao. 2004;16:227-229. ‎20.Guan ZX, Zhang XQ. Curative effects of composite Salvia miltiorrhiza bunge Pedr ‏ا‎ ever Arte fetO A tentep haf eV 2000;4:284. ‎aE Lp Cpe Be AN ges Meme UA ade MWe a eet Roy angina ppectoris. Zhongguo Linchuang Yixue.1999;6:21-2 ‎ 

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Dan ع طوه دمناءءزهذ معنطسهغائص مت«لم5 6ه ممق حروقطه عتمنات .1< ‎ORES‏ ‎PEO cL aan cee ULAR Ce SOT‏ 2003;22:13-15 23, Sun M, Zhang Jf, Shan JZ, et al. Clinical observation of Danhong Injection (herbal TCM product from Radix Salviae miltiorrhizae and Flos Carthami tinctorii) in the treatment of traumatic intracranial hematoma. Phytomedicine. 2009 Aug;16(8):683-9 24, Huang X, Jian H, Liu D, et al. Implantation of calcium phosphate ‏ی ی نت‎ auc teh femoral head. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2008 Mar;22(3):307-10. 25. Zhou JZ, Xiong P. Clinical observation of composite Danshen dipping pill on 100 patients with coroary heart disease. Linchuang DSi tod) if Cuno Aviv OAc PIPL eR nA tp ew Aamo cece romp omer ond interaction between warfarin and human serum albumin studied by ]- 7 cesta snon(lea gee Crmstleb VEC o mS i ccolnes) 2008; Oct: 1568-75 معة .ممطمصة2 قصة متسم سمي موعتوؤفط دوتع و عغم] .110 صقطع .27 ‎Pharmacother. 2001;35:501-504.‏ 28. Gupta D, Jalali M, Wells A, et al. Drug-herb interactions: ‏عاط كمه وممصم اعطكطةط م256 يه دمتكدم7 رصي 60160 0تع صن‎ salicylate. J Clin Lab Anal.2002;16:290-294 

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Sangi (Panax notoginseng) 

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تمصحو = The root of Panax Notoginseng = It is the largest ingredient in QU00 ( Yunnan Bai Yao), a famous hemostatic herbal remedy = Sweet and slightly bitter in taste, and nontoxic. = The dose in decoction for clinical use is 5-10 g. It can be ground to powder for swallowing directly or taking mixed with water: the dose in that case is usually is 1-3 grams. 

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Sangi 1. Action and Indications in TCM (1) Stops bleeding and transforms blood stasis: Used for internal and external bleeding (2) Reduces swelling and alleviates j oye boas 

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Sangi 2. Chemical constituents. = Saponins derivatives (PNS), which is a mixture of more than 20 types of saponins, four or five of them are considered as the principle active ones = Notoginenoside R1, ginsenoside Rg1, Rd, Re and Rb1 (75-80% total PNS) = Flavonoids et al. 

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Sanqi 3. Pharmacokinetics = Oral administration, most Saponins derivatives (powder) tested in rats, reached peak concentration in plasma rapidly within about 0.75 h - hint their absorption were quick. = Maximum concentration in rat plasma ۱۵۵ 4 "= indicated that it may be poorly absorbed and / or extensive metabolized (intestinal microflora, liver) 

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San-qi " Half time was changed from 1 to 20 hrs in rat plasma after oral administration of the constituents = [vin rats, most constituents were cleared quickly except a couple of PNS = the pharmacokinetic profile diversities of these constituents are probably one of the mechanisms of the multiple pharmacology activities 

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San-qi 4. Actions and indications in Herbal pharmacology (1)Hemostatic effect San-qi and a saponin (PNS) extract provide hemostatic effects. External application reduces bleeding timea). 

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San-qi (2)Thrombogenicity effects =PNS reduces platelet activation, adhesion and aggregationo, = Prevent thrombosis and improve microcirculation in patients with blood hyperviscosicity syndromes). 

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San-qi (3)Thrombogenicity effects =PNS iv or oral 200 mg/kg need 20 days to appear "hint a slow effect compare to hemostatic 

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San-qi CO lien Aan Cems nKra ny =Sanqi (the extract as notoginsenoside R1) increased the fibrnolytic potential in in vivo lab test, which may be beneficial to cardiovascular diseasew 

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San-qi (5)Cardiovascular effects = Dilate the coronary artery, increase coronary blood flow, providing more blood to the heart muscle = Improves micro-circulation in and around damaged heart tissue =™ Reduces cardiac load, lowers arterial pressures) 

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San-qi ™ Decrease the size of myocardial infarction = Anti-arrhythmia =PNS increases PGI2 and reduces thromboxane A2 in platelets — correct the unbalance between the two prostaglandins 

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(6)Anti-atherosclerotic “"* ۰۰۲ =It helps lower cholesterol and triglycerides, to prevent the progression of atherosclerotic lesion. PNS possess anti-hyperglycemic and anti-obese activities by improving insulin- and leptin sensitivity, and Rb1 is responsible for the anti- hyperglycemic effect among the five saponins in KK-Ay mice.e,7) 

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San-qi (7) Effects on brain ۱ = Protect ischaemic brain damagew). Ginsenoside Rb(3) could markedly protected OGD-Rep induced ischemic injury and the mechanisms maybe related to its suppression of the intracellular Ca(2+) elevation and inhibition of apoptosis and caspase activity. Ginsenoside Rb(3) could be a promising candidate in the development of a novel class of anti-ischemic agent. = Decrease brain edema, infarct size and neuron ۹ = Inhibit uptake calcium by neuron cells isolated from rats = Protect cultured rat cortical neuron from glutamate neurotoxicity 9) 

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San-qi (8)Tumor Radio-sensitivity Taiwanese scientists studied the sensitization effect of Panax notoginseng extract and purified Saponin (Rb1) on the radiation response of an experimental tumor (KHT sarcoma) in comparison with its effects on a normal tissue (bone marrow) in mice. 

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San-qi = Panax notoginseng extract at a concentration of 0.1-100 mg/kg produced an increase in tumor radiosensitivity. = Rb1 at a concentration 0.001 to 1 mg/kg produced an increase in tumor ‏ات ا لان الت ا‎ mg/kg. = The effect was maximal at 10 mg/kg and at 30 minutes after injection. = Further purified or synthetic versions are useful in cancer therapy. 

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(9)Anti-inflammatory effects and stop pain = San Qi can stop pain caused by inflammation and trauma through anti- inflammation and disturbing the central nervous system. 5. Toxicity = Low = Esophagitis from consuming tablets (drink enough water) may occur = Allergic reactions including dermatitis, shock, purpura, blisters, or other idiosyncratic reactions. 

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6. Clinical research (1)Coronary artery disease (2)Hyhercholesterolemia (3)Bleedings: = Upper gastointerestinal bleeding = Stomach bleeding = Hemoptysis = Pain 

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Sanqi Reference: 1.Fan C, Song J, White CM.A comparision of the hemostatic effects of notoginseng and yun nan bai yao to placebo control. J Herb Pharmacother. 2005;5(2):1-5. 2. Lau AJ, Toh DF, Chua TK, et al. Antiplatelet and anticoagulant effects of Panax notoginseng: comparison of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium. J Ethnopharmacol. 2009 Sep 25;125(3):380-6. Epub 2009 Aug 7. 3.Wang J, Xu J, Zhong JB. Effect of Radix notoginseng saponins on platelet activating molecule expression and aggregation in patients with blood hyperviscosity syndrome. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Apr;24(4):312-6. 4.Zhang WJ, Wojta J, Binder BR. Effect of notoginsenoside R1 on the synthesis of components of the fibrinolytic system in cultured smooth muscle cells of human pulmonary artery. Cell Mol Biol. 1997 Jun;43(4):581-7. 5. Wu L, Zhang W, Tang YH, et al. Effect of total saponins of “panax notoginseng root" on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in rats. Phytomedicine. 2010 Mar;17(3-4):233-40. 

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Sanqi 6.Yang CY, Wang J, Zhao Y, et al. Anti-diabetic effects of Panax notoginseng saponins and its major anti-hyperglycemic .20:130)2(:231-6 تال 2010 .امعفمصقطممصط8 [ .متسمعدممصرمء ‎7.Liu G, Wang B, Zhang J, et al. Total panax notoginsenosides‏ PsA ‏در‎ of downregulation of CD40 and MMP-9 expression.J Ethnopharmacol. 2009 Nov 12;126(2):350-4. 8. Zhu JR, Tao YF, Lou S, et al. Protective effects of ginsenoside ‏هر بای رت هرد ناذا‎ tele eenaremconetebrl tag in PC12 cells. Acta Pharmacol Sin. 2010 Mar;31(3):273-80. 9. Cai BX, Li XY, Chen JH, et al. Ginsenoside-Rd, a new voltage- ۱ ‏ا ا‎ 0 ‏م ا‎ emt aN Pharmacol. 2009 Mar 15;606(1-3):142-9. 

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Chuan Xiong (Rhizoma Ligustici Chuanxiong) 

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9 Chuanxiong is the root and rhizome of Ligusticum Chuangxiong Hort Properties: Acrid, warm. Channels entered: Liver, pericardium, and gallblader. 1. Actions and indications in TCM a) (1)Regulate Qi and invigorates the blood It is widely used for irregular menstruation, menorrhea, dysmenorrhea, and headache due to qi stagnation and blood stasis. (2)Expel wind and relieve pain It is used for headache, aching body and Bi syndrome due to wind cold. 

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2. Major Chemical Ingredients.) ‏بت‎ Alkaloids: Chuanxiongzine, tetramethylprazine, Organic acid: Ferulic acid, sedanonic acid, Essential oil: ethyl pentadecanoate, 3. Pharmacological effects,,3) 1)Cardiovascular«) Chuan Xiong dilates blood vessels, increases myocardial blood flow and oxygen-supply, keeps myocardial oxygen balance. The mechanism is related to ChuanXiong decreases invascular endothelial growth factor (VEGF) expression. ( 

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وصمةة مسقنت (2). Improves the circulation = Dilates arteries: dilates the arteries of the heart, brain, lungs: for example, increases blood perfusion to and reduce swelling of the brain. Used for migraine, cerebral ischemia, Alzheimer’s disease. = Antiplatelet and anticoagulant: 

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(3)Stop pain ™ Sedative: effects on the central nervous system = Relaxes the spasm of muscles ۱۳2 ™ Decreases the side effects of kanamycin and cyclosporin A = Anti-radiotherapy: 

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4. Herb-drug al 1۳۱۵۲۵0101۵ = Antiplatelet and anticoagulat: Though this potential interaction has not been documented, it should be used with caution. Examples of antiplatelet are aspirin, dipyridamole(persantine), and clopidogrel(plavix). Examples of anticoagulat are heparin, wafarin(coumadin), and enoxaprin(lovenox). 

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00000 5. Toxicologyes = When continuous oral administrated in mice with 5mg-10mg/kg for 4 weeks, no abnormalities of liver, kidney, blood exam. and pathological exam were observed. = The LD50 for it preparation in mice was 66.42g/kg with intravenous injection. 

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6. Clinical Indication of Research = Headache = Diseases of the heart and brain 

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Chuan Xion¢ Reference: 1.Qian Xin-zhong. Chinese Materia Medica. People’s Medical Publishing House. 2007.Beijing 2. Shen Yin-jun. Chinese Herbal Pharmacology. People’s Medical Publishing House. 2000.Beijing 3. John Chen, Tina T Chen. Chinese Medical Herbology and Pharmacology. Art of Medicine Press, Inc. 2009. City of Industry, CA. 4. Meng H, Guo J, Sun Jy, et al. Angiogenic effects of the extracts from Chinese herbs: Angelica and Chuanxiong. Am J Chin Med. 2008;36(3):541-54. 

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ey Thank You !