Danshen Medicine Researches
Comparative study of compound danshen dripping pills and sordi in
treatment of patients with chronic stable angina
Fourth Affiliated Hospital of Hebei Medical College, Shijiazhuang.
OBJECTIVE: To observe the effect of Compound Dansen Dripping Pills (CDDP)
in treating chronic stable angina. METHODS: The effect of oral CDDP and
Sordi were compared with those of placebo in 64 patients with chronic
stable angina. Patients performed symptom limited multistage, supine
bicycle ergometric exercise, while undergoing non-imaging radionuclide
angiocardiographic examination after 8 week periods treatment of 10-15
pills, three times daily, 10-15 mg Sordi three times daily, and placebo.
All drugs were given double blind and randomly. Adverse effects that
occurred during drug treatment were minor and generally well tolerated.
RESULTS: CDDP not only appeared to be more effective than Sordi in
increasing exercise duration and delaying time of onset of exercise
angina or peak effort, but also seems to be superior to Sordi in
improving either the stress-induced myocardial ischemia or the exercise
left ventricular systolic function. CONCLUSION: CDDP is a more effective
drug in treating chronic stable angina.
Clinical study of diabetic retinopathy treated by compound danshen
dripping pills
Qi CX, Tan XH, Li QG, Wang XL.
Department of Ophthalmology, Affiliated Third Hospital, Sun Yat-sen
University, Guangzhou 510630, China.
OBJECTIVE: To observe the therapeutic effect of compound danshen
dripping pills in visual function recovery of diabetic retinopathy.
METHODS: 42 patients(78 eyes) with diabetic retinopathy of I-III phase
were divided into two groups in random. 43 eyes were treated with
compound danshen dripping pills and the other 35 eyes with vitamin BI
and Luding C for three months. The visual acuity, fundus, visual field,
fundus fluorescein angiography and visual electro-physiology were
observed. RESULTS: The visual acuity in treated group were significantly
improved after treatment and had significant difference with those in
control group (P < 0.05). The number of micro-hemorrage, microaneurysm
and the mean defect (MD) of visual field in treated group decreased
obviously after treatment and had significant difference with that in
control group (P < 0.05). The latent period of P100 wave and a, b wave
in treated group were shorter than control group, and the wave amplitude
were higher than that in control group. CONCLUSION: The compound danshen
pills can improve the visual acuity, control the micro-hemorrage and
microaneurysm of fundus and have the effect in visual function recovery
of diabetic retinopathy.
Clinical investigation of Compound Danshen Dripping
Pills for the treatment of angina pectoris.
Guo ZhiXin, Jia Wei, Gao WenYuan, Xu ZhaoHui, Zhao LiBin, Xiao PeiGen
Research Institute of Tianjin Tasly Group Co. Ltd., Tianjin 300402, China.
Chinese Journal of Natural Medicines, 2003 (Vol. 1) (No. 2) 124-128
Compound Danshen Pill (CDP) is a herbal drug for the treatment of angina
pectoris, which consists of herbal ingredients extracted from Salvia
miltiorrhiza, Panax notoginseng [P. pseudoginseng var. notoginseng] and
Cinnamomum camphora. The product is prepared by blending herbal extracts and
excipients under thermal conditions, and dripping the mixture into an insoluble
cooling liquid in which the droplets are rapidly solidified. Clinical studies
revealed that CDP is similar to nitroglycerin in its ability to relieve pain
rapidly. Clinical results also indicated that the long-term administration of
CDP can increase the pain-relief rate and electrocardiogram improvement rate,
and that its overall curative effect is superior to isosorbide dinitrate. A
multi-centre clinical investigation showed that this new dosage form of
composite Danshen is more effective in treating coronary heart disease than the
tablet form due to the improved bioavailability.
Enhanced antioxidant bioactivity of Salvia miltiorrhiza (Chinese Medicine Danshen) products prepared using nanotechnology.
Liu JR, Chen GF, Shih HN, Kuo PC.
Phytomedicine. 2008 Jan;15(1-2):23-30.
Department of Animal Science and Technology and Institute of Biotechnology,
National Taiwan University, Taipei 102, Taiwan, ROC.
The traditional Chinese medicine, Salvia miltiorrhiza (Danshen), promotes blood
circulation and relieves blood stasis, also demonstrating good antioxidant
activity. In the present study, therefore, the antioxidant activities of
medicinal plant materials prepared using nanotechnology or traditional grinding
methods were compared using three biological assays. It was found that the
nanotechnology preparation had stronger antioxidant bioactivities. Complementary
quantitative analysis of four active constituents, salvianolic acid B,
cryptotanshinone, tanshinone I and tanshinone IIA, by HPLC revealed only marked
differences for salvianolic acid B. The results indicate that the polar active
constituent in the nanotechnology samples was released faster compared to the
traditionally powdered samples.
Physicochemical properties and drug release rate of
calcium phosphate cement containing danshen composite injection
Jiang H, Huang X, Tan Y.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007 Oct;21(10):1113-7.
Institute of Composite Material, Tianjin University, Tianjin 300072, PR China.
OBJECTIVE: To investigate the physicochemical properties of the calcium
phosphate cement (CPC) containing Danshen composite injection and its drug
release rate. METHODS: This experiment included 4 groups and each group
contained 6 specimens. CPC (2 g) was mixed with the setting solution that served
as the control group; 0.1, 0.5 and 1.0 ml of Danshen composites injection
(concentration, 1 000 mg/ml; pH, 7.35) were respectively added to CPC (2 g),
which were used as the experimental groups 1, 2 and 3. The resulting specimens
were investigated by the X-ray diffraction (XRD), the fourier transformed
infrared spectroscopy (FTIR), and the scanning electron microscope (SEM).
RESULTS: The XRD analysis showed that the control group had a typical
diffraction pattern of the hydroxypatite (HAP), which was consistent with the
standard pattern of HAP. When more Danshen was added in the experimental groups,
the diffraction peaks of HAP gradually decreased; when the diffraction angle
2theta was about 25.92 degrees, the HAP peaks disappeared. Based on the FTIR
analysis, with an increase of the drug concentration, the absorption peak of the
hydroxy groups decreased. The SEM showed that the size of the CPC particle was
related to the drug concentration; with an increase of the drug concentration,
the CPC particle increased in number, resulting in an increasing trend of
coacervation. The elution test showed that the drug-release rate and capacity
varied with the different concentrations of Danshen medicine. The initial
release rate was relatively great, but after 96 hours the rate slowed down,
lasting for a long time. CONCLUSION: The physicochemical properties of CPC do
not change when a proper dose (0.1 ml/2 g) of Danshen is added to CPC. The
Danshen composite can be effectively released from CPC, and so CPC can be used
as an ideal drug-delivery carrier for Danshen composite.
Cardiovascular effects of Danshen
Tsung O. Cheng,
Department of Medicine, The George Washington University Medical Center, 2150
Pennsylvania Avenue, N.W., Washington, D.C. 20037, United States
Danshen is one of the most versatile Chinese herbal drugs that have been used
for hundred of years in the treatment of numerous ailments. Because of its
properties of improving microcirculation, causing coronary vasodilatation,
suppressing the formation of thromboxane, inhibiting platelet adhesion and
aggregation, and protecting against myocardial ischemia, it is widely used
either alone or in combination with other herbal ingredients for patients with
coronary artery disease and other cardiovascular diseases, in both China and
other countries including the United States. This article provides an overview
of its history, pharmacology, pharmacokinetics, clinical applications, side
effects, interactions with Western drugs, and future prospects in the management
of cardiovascular diseases.
Ursolic acid from the Chinese medicine Danshen (Salvia
miltiorrhiza L.) upregulates eNOS and downregulates Nox4 expression in human
endothelial cells
Katja Steinkamp-Fenskea, Larissa Bollingera, Natalie Völlera, Hui Xua, Ying
Yaoa, Rudolf Bauerb, Ulrich Förstermanna, Huige Lia,
a. Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher
Strasse 67, D-55131 Mainz, Germany
b. Department of Pharmacognosy, Karl Franzens University, Graz, Austria
Danshen, the dried root of Salvia miltiorrhiza Bunge (Lamiaceae), is one of the
most commonly used traditional Chinese medicines for cardiovascular indications.
In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial
cells (HUVEC), an aqueous extract of Danshen, and also a methanol extract of the
plant, increased eNOS promoter activity, eNOS mRNA and protein expression, as
well as endothelial NO production. A dichloromethane extract, in contrast, did
not change eNOS gene expression. Thus, the active Danshen constituent(s)
responsible for eNOS upregulation is (are) hydrophilic and/or alcohol-soluble.
One such compound is ursolic acid that significantly increased eNOS expression
in EA.hy 926 cells and native HUVEC, and enhanced bioactive NO production
measured in terms of its cGMP increasing activity. Other tested hydrophilic and
alcohol-soluble compounds isolated from Danshen had no effect on eNOS
expression. Interestingly, ursolic acid also reduced the expression of the NADPH
oxidase subunit Nox4 and suppressed the production of reactive oxygen species in
human endothelial cells. Upregulation of eNOS and a parallel downregulation of
Nox4 lead to an increase in bioactive NO. This in turn could mediate some of the
beneficial effects of Danshen. Ursolic acid is a prototypical compound
responsible for this effect of the plant.
Relaxant effects of danshen aqueous extract and its
constituent danshensu on rat coronary artery are mediated by inhibition of
calcium channels
Francis Fu Yuen Lam, a, , John Hok Keung Yeunga, Kam Ming Chana and Penelope Mei
Yu Ora
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong
Kong, Shatin, New Territories, Hong Kong
In this study, we have investigated the actions of danshensu, an active,
water-extractable component of the medicinal herb danshen (Salvia miltiorrhiza),
on rat isolated coronary artery rings precontracted with 1 μM
5-hydroxytryptamine (5-HT) and its action compared to the water-extractable
fraction of the herb. Extraction of the water-soluble fraction from danshen (S.
miltiorrhiza) provided yield of 17.5% (35 g/200 g). The amount of danshensu
determined in the crude danshen herb and in its aqueous fraction was 0.45 mg/g
(0.045%) and 3.28 mg/g (0.33%). The danshen aqueous extract was 13 times less
potent than danshensu in relaxing 5-HT-precontracted coronary artery rings; IC50
values were 930.3 ± 133.5 μg/ml and 71.5 ± 11.0 μg/ml. Removal of the
endothelium did not significantly affect their vasodilator potencies; IC50
values were 842.1 ± 123.8 μg/ml and 84.8 ± 8.8 μg/ml. On the other hand, a
potassium channel inhibitor tetraethylammonium (TEA, 10 mM) shifted their
concentration–response curves by 1.7 and 2.2 folds. The possible involvement of
Ca2+ channels was investigated in artery rings incubated with Ca2+-free buffer
and primed with 1 μM 5-HT or 60 mM KCl for 5 min prior to addition of CaCl2 to
elicit contraction. In 5-HT-primed preparations, the CaCl2-induced
vasoconstriction was abolished by 2 mg/ml danshen aqueous extract and 200 μg/ml
danshensu, whereas, in KCl-primed preparations, 10 mg/ml danshen aqueous extract
and 600 μg/ml danshensu were required to abrogate the vasoconstriction. These
findings suggest the vasorelaxant actions of danshen aqueous extract and
danshensu were produced by inhibition of Ca2+ influx in the vascular smooth
muscle cells. The opening of K+ channels had a minor contribution to the
response, but endothelium-dependent mechanisms were not involved.
Danshen: A versatile Chinese herbal drug for the
treatment of coronary heart disease
Tsung O. Chenga,
aGeorge Washington University, Washington, DC 20037
Danshen: What every cardiologist should know about this Chinese herbal drug
Tsung O. Chenga,
aGeorge Washington University, Washington, DC 20037, United States
Danshen: A Popular Chinese Cardiac Herbal Drug
Tsung O. Cheng MD, , FACC
Journal of the American College of Cardiology, Volume 47, Issue 7, 4 April 2006,
Pages 1499-1500
John H.K. Vogel
Discriminating the Genuineness of Chinese Medicines Using Least Squares Support
Vector Machines
Ke Yua and Yiyu Cheng, a,
a.Pharmaceutical Informatics Institute, Zhejiang University, Hangzhou 310027,
China
A method for the rapid identification of the genuineness of Chinese medicines
based on near infrared (NIR) spectroscopy and least squares support vector
machines (LSSVM) was proposed. In this study, NIR spectra of the powdered
Danshen (Radix Salviae Miltiorrhizae) were collected, and the nonlinear
classifier based on LSSVM algorithm was developed to discriminate the
genuineness of these herbs. The result obtained by the proposed method was
compared with those from the traditional support vector machines (SVM) and
BP-ANN methods. It was shown that the generalization performance of the
classifier based on LSSVM was much better than that of BP-ANN, and the
computation time of LSSVM was much shorter than that of the traditional SVM. The
proposed method could be applied to the rapid and accurate identification of the
quality of the natural products.
Chinese herbs Danshen and Gegen modulate key early
atherogenic events in vitro
Daniel P. Sievekinga, , Kam-Sang Woob, Kwok P. Fungb, Pia Lundmana, Shirley
Nakhlaa and David S. Celermajera, c, d, ,
a.Heart Research Institute, 145 Missenden Rd, Camperdown, Sydney, NSW,
Australia, 2050
b.The Chinese University of Hong Kong, Hong Kong
c.Royal Prince Alfred Hospital Sydney, NSW, Australia
d.Department of Medicine, University of Sydney, Australia
Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) are two herbs used in
traditional Chinese medicine, most commonly for their putative cardioprotective
and anti-atherosclerotic effects. In this study, we investigated the effect of a
preparation of these herbs on two key processes in the early stages of
atherosclerosis; macrophage lipid loading and monocyte adhesion to endothelial
cells.
Human monocyte derived macrophages (HMDMs) were treated with 0.1–1.0 mg/ml of
the herbal mixture in aqueous buffers and loaded with acetylated LDL (AcLDL) (50
μg/ml) for 72 h, and analyzed for cholesterol (C) and cholesteryl esters (CE),
via HPLC. Human endothelial cell monolayers were also treated with 0.1–1.0 mg/ml
of the herbal mixture and monocyte adhesion measured. Cell adhesion molecules
E-selectin, ICAM-1 and VCAM-1 were assessed via ELISA.
Compared to control conditions, the herbal mixture induced a significant
dose-related decrease in the total cholesterol (free and esterified) in the
HMDMs (p<0.001 by ANOVA). By contrast, the herbs also induced an increase in
ICAM-1 expression (p<0.001) and monocyte adhesion at higher concentrations
(p<0.05).
In conclusion, treatment of cells with this preparation of Danshen and Gegen, a
commonly used Chinese health supplement, results in a dose-related suppression
of AcLDL uptake by human macrophages, and an increase in the level of ICAM-1
expression and adhesion of monocytes to endothelial cells. These herbs therefore
show the ability to modulate key early events in atherosclerosis.
Magnesium as NMDA receptor blocker in the traditional Chinese medicine Danshen
X. Suna, b, c, L.N. Chana, b and N.J. Suchera, b, d, ,
a.Department of Biology, Hong Kong University of Science & Technology, Clear
Water Bay, Kowloon, Hong Kong SAR, China
bMolecular Neuroscience Center, Hong Kong University of Science & Technology,
Clear Water Bay, Kowloon, Hong Kong SAR, China
c.Institute of Neuroscience, Nanjing Medical University, Nanjing, Jiangsu, China
d.Biotechnology Research Institute, Hong Kong University of Science &
Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China
Aqueous extracts of the traditional Chinese medicine Danshen, the dried roots of
Salvia miltiorrhiza Bunge (Labiatae), blocked N-methyl-d-aspartate (NMDA) evoked
currents in cerebrocortical neurons in vitro. The block of the NMDA-evoked
currents was voltage dependent and showed the negative slope conductance
reminiscent of the effect of Mg2+ ions. Atomic absorption spectrophotometry
(AAS) revealed that aqueous Danshen extracts contained 9 mM magnesium.
Fractionation of the extracts by high performance liquid chromatography followed
by patch clamp recording and AAS indicated that magnesium ions were present in
two distinct fractions. One fraction contained 5 mM magnesium and blocked
NMDA-induced currents indicating that it contained mostly free Mg2+ ions, while
a second fraction did not possess NMDA antagonist activity despite the presence
of 4 mM magnesium suggesting that Mg2+ in this fraction was mostly chelated.
Following removal of the free Mg2+ by ion exchange chromatography, the
previously observed block of the NMDA-induced currents was abolished. These data
demonstrate that Danshen contains both free and chelated Mg2+. Free Mg2+ ions
account for the NMDA antagonist activity of Danshen in vitro.
Protective effects of Danshensu from the aqueous
extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced
endothelial dysfunction
K. Chana, S.H. Chuia, D.Y.L. Wonga, W.Y. Haa, C.L. Chana and R.N.S. Wonga, b, ,
a.Research and Development Division, School of Chinese Medicine, Hong Kong
Baptist University, Hong Kong
b.Department of Biology, Science Faculty, Hong Kong Baptist University, Hong
Kong
Homocysteine (Hcy) is a by-product of methionine metabolism. An imbalance of Hcy
in the body may lead to hyperhomocysteinemia, a condition with elevated Hcy
concentration in blood that may be one of the risk factors responsible for the
development of several vascular diseases (thromboembolism, atherosclerosis,
stroke, vascular diseases and dementia). Radix Salvia miltiorrhiza (Danshen), a
well-known Chinese medicinal herb that can activate and improve blood
microcirculation, is noticeable for its beneficial effect in treating
cardiovascular diseases. The present study is to demonstrate the protective
effect of Danshen extract against the homocysteine-induced adverse effect on
human umbilical vein endothelial cell (HUVEC). Homocysteine (5 mM) not only
decreased the cell viability but also caused the disruption of capillary-like
structure formation in vitro. The protective effect of Danshen aqueous extract
and its active compounds on endothelial cell function were demonstrated through
an in vitro tube formation assay, which mimics the new blood vessel formation.
To identify the active components in the aqueous extract of Danshen, the content
was characterized by instrumental analysis using high performance liquid
chromatography with diode array detector (DAD) and electrospray tandem mass
spectrometry (ESI-MS/MS). Interestingly, Danshen extract and its pure compounds
showed different effectiveness in protecting HUVEC against Hcy-induced injury
according to the following descending order: Danshen aqueous extract,
3-(3,4-dihydroxy-phenyl)-2-hydroxy-propionic acid (Danshensu), protocatechuic
acid, catechin and protocatechualdehyde. We believed that such findings might
provide evidence in understanding the beneficial effects of Danshen on the
cardiovascular system.
Study of the determination and pharmacokinetics of
Compound Danshen Dripping Pills in human serum by column switching liquid
chromatography electrospray ion trap mass spectrometry
Wei-Jing Peia, Xin-Feng Zhaob, Zhong-Min Zhuc, Chang-Zheng Lind, Wen-Ming Zhaoa
and Xiao-Hui Zhengc, ,
a.Department of Biology Engineering, School of Life Science and Technology,
Xi’an Jaotong, University, Xi’an, ShaanXi, China
b.Science School of Xi’an Jiaotong University, Xi’an, ShaanXi, China
c.Engineering and Research Center of Chinese Herb Modernization, Xi’an Jiaotong
University, Xi’an, ShaanXi, China
d.Pharmacy Department of Second Hospital, Xi’an Jiaotong University, Xi’an,
ShaanXi, China
Compound Danshen Dripping Pill (CDDP) is an important drug widely used for the
treatment of cardiovascular diseases. An active component Danshensu (DS) of CDDP
was separated by reversed-phase high performance liquid chromatography using
column-switching system and analyzed by electrospray mass spectrometry. With
this validated assay the pharmacokinetics of CDDP was studied in 10 healthy
volunteers after a single oral administration of 250 mg. After trichloroacetic
acid precipitation of serum proteins, the analytes were preconcentrated and
black-flushed on a reversed-phase column for separation using a switching valve.
The analytes were ionized using negative electrospray ionization (ESI) mode. The
precursor ion of m/z 196.6 was used to quantify DS in serum. The linear
calibration curve ranged from 1.25 to 175 μg/mL. The limit of quantification
(LOQ) for DS was 0.15 μg/mL. The intra-day and inter-day precision (R.S.D.) was
less than 7.4 and 7.9%, respectively.
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