Chinese medicine for hypertension research
[Analysis on clinical treatment in hypertension by traditional Chinese medicine for 10 years in Beijing]
Zou ZD, Liu N, Guo P, Guo LY, Sun Y, Shi J, Wang L.
College of Traditional Chinese Medicine, Capital Medicinal University, Beijing 100069, China.
To make a retrospective study of clinical treatment in hypertension by traditional Chinese medicine for 10 years in Beijing, and to mainly analyze in three facets: the study on total regularity of using Chinese herbal medicine, the study on regularity of application, and the study on differentiation of symptoms and signs. RESULT: (1) Total regularity of using Chinese herbal medicine: They are tonic herbs, expelling phlegm and stopping winding herbs, heat-clearing herbs, blood-activating and stasis-resolving herbs, damp-clearing herbs in turn. The frequently used herbs were gouteng, niuxi, tianma, fuling, baishao, zexie, chuanxiong, and so on. (2) The study on regularity of application: The 6 kinds of herbs above were abide by the total regularity and the frequently used herbs were gouteng, niuxi, fuling, tianma, chuanxiong, baishao, zexie, and so on. (3) It was showed that the common syndromes of hypertension and herbs were: The herbs such as gouteng, niuxi, baishao, tianma, chuanxiong, juhua were frequently used in liver yang ascending syndrome. Herbs such as gouqizi, niuxi, shanyao, shudihuang, fuling, mudanpi, were frequently used in symptoms of yin deficiency of liver and kidney. Herbs such as huangqin, xiakucao, gouteng, zhizi, longdancao, juhua were frequently used in syndrome of flarming liver-fire. Herbs such as fuling, banxia, jupi, baizhu, tianma, gancao were frequently used in the stagnation of phlegm. Herbs such as tianma, gouteng, baishao, shijiuming, banxia were frequently used in up-stirring of liver. Herbs such as chuanxiong, chishao, honghua, danshen, sanqi were frequently used in syndrome of blood stasis in the collateral of the brain. Herbs such as shanzhuyu, shudi, fuling, rougui, fuzi, niuxi were frequently used in both-yini-and-yang-deficiency.

Clinical and experimental study of effect of Raondix Salviae Militiorrhiza and other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.
Yao XX, Cui DL, Sun YF, Li XT.
Department of Internal Medicine, Second Affiliated Hospital,Hebei Medical University, Shijiazhang 050000, Hebei Province, China.
AIM:To study the effects of Radix Salviae Militiorrhiza (RSM), other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.METHODS:Portal pressure of cirrhotic dogs after chronic common bile duct ligation was measured directly; portal blood flow in patients with liver cirrhosis were detected by ultrasound Doppler.RESULTS:After administration of RSM and Radix Angelicae Sinensis (RAS) by intravenous infusion in cirrhosis dogs, the portal venous pressure (Ppv), wedge hepatic venous pressure (WHVP), hepatic venous pressure gradient (HVPG), were significantly decreased (P < 0.05-0.01), but the mean arterial pressure (MAP), and the heart rate (HR) remained unchanged. When nifedipine was used, Ppv, WHVP, MAP and HR were significantly decreased (P < 0.05), and the MVPG unchanged (P > 0.05). After administration of RSM, RSM+nifedipine and RSM+Hirudin+Nifedpin for 10-12 weeks, the diameter of portal vein (Dpv), spleen vein (Dsv), the portal venous flow (Qpv) and splenic venous flow (Qsv) in patients with hepatic cirrhosis were significantly lowered (P < 0.05-0.01), and the effect of RAS was weaker.CONCLUSIONS: The efficacy of decreasing Ppv by Chinese herbs RSM, RAS, etc. as compared with nifedipine, demonstrated that the Chinese herbs were slower in action than that of nifedipine, but more long-lasting and without side effects. Hence, long-term administration of Chinese herbs, would be more beneficial.

Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides.
Yue PY, Mak NK, Cheng YK, Leung KW, Ng TB, Fan DT, Yeung HW, Wong RN.
Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.
In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions. Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg1 and Rb1. Rg1 was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K-->Akt pathway. By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3 and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These lines of evidence support that the interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse pharmacological activities of ginseng. These findings may also lead to development of more efficacious ginseng-derived therapeutics for angiogenesis-related diseases.

Zhi-fuzi, a cardiotonic Chinese herb, a new medical treatment choice for portal hypertension?
Lin JS, Chan CY, Yang C, Wang YH, Chiou HY, Su YC.
School of Chinese Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan 40421.
Zhi-Fuzi (Radix Aconiti lateralis preparata) is prescribed fairly frequently in Chinese medicine clinical practice for treating the complications of cirrhosis. However, scientific evidence regarding its efficacy and safety has not been available until now; in addition, its treatment efficacy has not yet been evaluated in well-designed clinical trials. Hence, we investigated the hemodynamic effects of Zhi-Fuzi in conscious rats with portal vein ligation (PVL) and the safety in normal rats. Our study included 3 parts: (i) early administration during which the hemodynamic effects of low and high doses of Zhi-Fuzi (0.4 and 0.8 g/kg twice daily) and propranolol (15 and 30 mg/kg twice daily) administered for 14 days after PVL on male Sprague-Dawley rats were evaluated; (ii) late administration during which the other group of PVL rats received 2.4 g/kg of Zhi-Fuzi twice daily from the 15th to 28th postoperative day; hemodynamic effects were measured when the Zhi-Fuzi treatment was finished; and (iii) safety evaluation during which 2 groups of normal rats were administered Zhi-Fuzi (0.4 and 0.8 g/kg twice daily) for 14 days; biochemical and histopathologic studies were completed after hemodynamic measurement. In early administration the portal pressures in rats receiving low and high doses of Zhi-Fuzi, low and high doses of propranolol, and distilled water were 13.81 +/- 0.11, 11.59 +/- 0.07, 17.09 +/- 0.06, 14.52 +/- 0.29, and 20.11 +/- 0.22 mm Hg, respectively. The high dose of Zhi-Fuzi exerted more portal hypotensive effects than propranolol and simultaneously ameliorated the systemic arterial hypotension in PVL rats. The late administration of Zhi-Fuzi also significantly reduced the elevated portal pressure (14.56 +/- 0.19 vs. 19.50 +/- 0.31 mm Hg in control, P < 0.05). There were no adverse effects seen in normal rats receiving Zhi-Fuzi. The results suggest that Zhi-Fuzi is a potential drug for the prophylaxis and treatment of portal hypertension.

Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension.
Kim DD, Sˆhnchez FA, Durˆhn RG, Kanetaka T, Durˆhn WN.
Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07101-1709, USA.
Danshen, a Chinese herb, reduces hypertension in Oriental medicine. We hypothesized that Danshen acts partially through endothelial nitric oxide synthase (eNOS) signaling mechanisms. We tested the hypothesis using tanshinone II(A), an active ingredient of Danshen, and the two-kidney, one-clip renovascular hypertension model in hamsters. Oral tanshinone (50 microg/100 g body wt) reduced mean arterial pressure (MAP) from 161.2 +/- 6.9 to 130.0 +/- 7.8 mmHg (mean +/- SE; P < 0.05) in hypertensive hamsters. MAP in sham-operated hamsters was 114.3 +/- 9.2 mmHg. Topical tanshinone at 1 microg/ml and 5 microg/ml increased normalized arteriolar diameter from 1.00 to 1.25 +/- 0.08 and 1.57 +/- 0.11, respectively, and increased periarteriolar nitric oxide concentration from 87.1 +/- 11.3 to 146.9 +/- 23.1 nM (P < 0.05) at 5 microg/ml in hamster cheek pouch. N(G)-monomethyl-L-arginine inhibited tanshinone-induced vasodilation. Hypertension reduced eNOS protein relative to sham-operated control. Tanshinone prevented the hypertension-induced reduction of eNOS and increased eNOS expression to levels higher than sham-operated control in hamster cheek pouch. Topical tanshinone increased normalized arteriolar diameter from 1.0 to 1.47 +/- 0.08 in the cremaster muscle of control mice and to 1.12 +/- 0.13 in cremasters of eNOS knockout mice. In ECV-304 cells transfected with eNOS-green fluorescent protein, tanshinone increased eNOS protein expression 1.35 +/- 0.05- and 1.85 +/- 0.07-fold above control after 5-min and 1-h application, respectively. Tanshinone also increased eNOS phosphorylation 1.19 +/- 0.07- and 1.72 +/- 0.20-fold relative to control after 5-min and 1-h application. Our data provide a basis to understand the action of a Chinese herb used in alternative medicine. We conclude that eNOS stimulation is one mechanism by which tanshinone induces vasodilation and reduces blood pressure.

[Ligustrazine and Salvia miltiorrhiza injection solution in complementary therapy of pregnancy-induced hypertension: clinical analysis of 60 cases]
Wang XF, Zhao MQ.
Department of Obstetrics and Gynecology, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China.
OBJECTIVE: To compare the clinical effects of ligustrazine and Salvia miltiorrhiza injection solutions in the complementary therapy of pregnancy-induced hypertension (PIH). METHODS: Sixty patients with PIH were equally divided into 2 groups to receive intravenous infusion of 80 mg ligustrazine and 16 ml Salvia miltiorrhiza injection solution respectively, in addition to the conventional therapies. The effects of the two complementary treatments were compared. RESULTS: After a treatment course of 10 days, ligustrazine produced obvious effect in inhibiting fibrinolysis and promoting microcirculation of the patients. Salvia miltiorrhiza injection resulted in obvious reduction of blood viscosity, cholesterol and lipoprotein. CONCLUSION: Ligustrazine and Salvia miltiorrhiza injections produce obvious therapeutic effects on PIH, but they are used for different clinical purposes as their in pharmacological action difference.

Effect of Salvia miltiorrhiza on left ventricular hypertrophy and cardiac aldosterone in spontaneously hypertensive rats.
Han S, Zheng Z, Ren D.
Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030.
Chronic treatment with Salvia Miltiorrhiza(Chinese medicine for hypertension) preventing left ventricular hypertrophy (LVH) and its possible mechanism--inhibiting the action of cardiac aldosterone in spontaneously hypertensive rats (SHR) were investigated. Normotensive Wistar-kyoto (WKY) rats and SHRs were used. Part of SHRs was treated with Salvia Miltiorrhiza for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index were measured. Sections of heart tissue were stained with HE method and VanGieson method. Collagen volume fraction was determined in the left ventricle by automatically quantitative morphometry. Cardiac aldosterone concentration was measured by radioimmunoassay. The results indicated that compared with WKY rats, SHRs exhibited higher SBP, left ventricular collagen volume fraction, and aldosterone concentration (all P < 0.05). After the treatment with Salvia Miltiorrhiza, SBP, left ventricular collagen volume fraction, and aldosterone concentration in SHR were decreased as compared with control group (P < 0.05) except SBP. It was concluded that chronic treatment with Salvia Miltiorrhiza could prevent left ventricular hypertrophy in SHR, significantly inhibit collagen compositions in left ventricle. The mechanism was probably related with the inhibition of the cardiac aldosterone action.

Anti-hypertensive effect of water extract of danshen on renovascular hypertension through inhibition of the renin angiotensin system.
Kang DG, Yun YG, Ryoo JH, Lee HS.
Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Chonbuk, Korea.
A study was designed to elucidate the mechanism of anti-hypertensive effects of danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of danshen extract for three weeks. These results suggest that danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.

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