Danggui Buxue Tang (Astragali Radix and Angelicae Sinensis Radix) for menopausal symptoms: A review.

BACKGROUND: Traditional Chinese medicine (TCM) has contributed greatly to human health in past several thousand years. Today, the development of TCM is facing two obstacles: (i) quality control of herbal extract; and (ii) action mechanisms not known. OBJECTIVES: Among thousands of complex TCM formulations, Danggui Buxue Tang (DBT) is the simplest one. DBT is used to treat ailments in women and contains only two herbs, Astragali Radix (Huangqi; AR) and Angelicae Sinensis Radix (Danggui; ASR). The weight ratio of AR to ASR in DBT must be 5:1, as stipulated in AD 1247. By using DBT as a model formula, we develop a strategy to reveal the complexity of a traditional TCM formula. RESULTS: There are 3 levels of research directions: (i) the preparation of DBT and its rationale behind; (ii) the traditional theory of DBT is elucidated by chemical and biological determinations; and (iii) the action mechanisms of DBT are revealed. CONCLUSION: Through the chemical, biological, genomic and proteomic studies, a possible direction in resolving the preparation mythologies, pharmacological and mechanistic analyses of a TCM decoction is being proposed here.

A chinese herbal decoction, danggui buxue tang, stimulates proliferation, differentiation and gene expression of cultured osteosarcoma cells: genomic approach to reveal specific gene activation.

Danggui Buxue Tang (DBT), a Chinese herbal decoction used to treat ailments in women, contains Radix Astragali (Huangqi; RA) and Radix Angelicae Sinensis (Danggui; RAS). When DBT was applied onto cultured MG-63 cells, an increase of cell proliferation and differentiation of MG-63 cell were revealed: both of these effects were significantly higher in DBT than RA or RAS extract. To search for the biological markers that are specifically regulated by DBT, DNA microarray was used to reveal the gene expression profiling of DBT in MG-63 cells as compared to that of RA- or RAS-treated cells. Amongst 883 DBT-regulated genes, 403 of them are specifically regulated by DBT treatment, including CCL-2, CCL-7, CCL-8, and galectin-9. The signaling cascade of this DBT-regulated gene expression was also elucidated in cultured MG-63 cells. The current results reveal the potential usage of this herbal decoction in treating osteoporosis and suggest the uniqueness of Chinese herbal decoction that requires a well-defined formulation. The DBT-regulated genes in the culture could serve as biological responsive markers for quality assurance of the herbal preparation.

The expression of erythropoietin triggered by danggui buxue tang, a Chinese herbal decoction prepared from radix Astragali and radix Angelicae Sinensis, is mediated by the hypoxia-inducible factor in cultured HEK293T cells.

ETHNOPHARMACOLOGICAL EVIDENCE: Danggui buxue tang (DBT), a Chinese medicinal decoction that is being commonly used as hematopoietic medicine to treating woman menopausal irregularity, contains two herbs: radix Astragali and radix Angelicae Sinensis. Pharmacological results indicate that DBT can stimulate the production of erythropoietin (EPO), a specific hematopoietic growth factor, in cultured cells. AIM OF THE STUDY: In order to reveal the mechanism of DBT's hematopoietic function, this study investigated the activity of the DBT-induced EPO expression and the upstream regulatory cascade of EPO via hypoxia-induced signaling in cultured kidney fibroblasts (HEK293T). MATERIALS AND METHODS: DBT-induced mRNA expressions were revealed by real-time PCR, while the change of protein expressions were analyzed by Western blotting. For the analysis of hypoxia-dependent signaling, a luciferase reporter was used to report the transcriptional activity of hypoxia response element (HRE). RESULTS: The plasmid containing HRE, being transfected into HEK293T, was highly responsive to the challenge of DBT application. To account for the transcriptional activation of HRE, DBT treatment was shown to increase the mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α). In addition, the activation of Raf/MEK/ERK signaling pathway by DBT could also enhance the translation of HIF-1α, suggesting the dual actions of DBT in stimulating the EPO expression in kidney cells. CONCLUSION: Our study indicates that HIF pathway plays an essential role in directing DBT-induced EPO expression in kidney. These results provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function.

Can rhizoma chuanxiong replace radix Angelica sinensis in the traditional Chinese herbal decoction danggui buxue tang?

Herein, we test the hypothesis that a member of a formulated Chinese herbal decoction cannot be replaced by another herb. Danggui Buxue Tang (DBT) is being used as an example for illustration: this is a traditional decoction containing Radix Astragali (RA) and Radix Angelicae Sinensis (RAS) in a weight ratio of 5 to 1. Rhizoma Chuanxiong (RC) and RAS are two chemically very similar herbs but with a distinct function. Following the preparation method of DBT, a herbal decoction, namely Chuanxiong Buxue Tang (CBT), was created, which contained RA and RC in a weight ratio of 5 to 1. The two decoctions, DBT and CBT, were compared in parallel regarding their chemical and biological properties. In all the tested parameters, DBT showed superior properties, both chemically and biologically, to that of CBT. The current results reveal the uniqueness of Chinese herbal decoctions that require a well-defined formulation, which is indispensable for its specific composition.

A Chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis induces the expression of erythropoietin in cultured Hep3B cells.

Danggui Buxue Tang (DBT), a Chinese medicinal decoction used commonly for treating women's ailments, contains Radix Astragali (RA) and Radix Angelicae Sinensis (RAS). According to Chinese medicinal theory, this decoction is to nourish the blood function; this, however, has not been demonstrated on the molecular level. In order to reveal the hematopoietic effect of this decoction, DBT was applied to cultured Hep3B human hepatocellular carcinoma cells. The treatment of DBT induced mRNA expression of erythropoietin (EPO) in a dose-dependent manner and peaked at approximately 2.5-fold induction. The secreted EPO in cultured Hep3B cells was quantified by ELISA: the treatment of DBT potentiated the effect of hypoxia-induced EPO expression in the cultured cells. In addition, the DBT-induced EPO expression could be abolished by pre-treatment with U0126, a mitogen-activated kinase inhibitor. The current results verified the hematopoietic function of this ancient herbal decoction.

A Chinese herbal decoction, Danggui Buxue Tang, activates extracellular signal-regulated kinase in cultured T-lymphocytes.

Danggui Buxue Tang (DBT) is prepared from Radix Astragali and Radix Angelicae Sinensis. This Chinese herbal decoction has been shown to stimulate the proliferation of T-lymphocytes; however, the action mechanism of this stimulation has not been revealed. In cultured T-lymphocytes, application of DBT markedly induced the cell proliferation, the release of interleukin-2, -6 and -10, as well as the phosphorylation of extracellular signal-regulated kinases (ERK). The pre-treatment of ERK inhibitor blocked the DBT-induced immune responses. In addition, the polysaccharide-enriched fraction of DBT showed marked responses on the cultured T-lymphocytes suggesting the important role of DBT polysaccharide in triggering such immune responses.

Danggui buxue tang--a Chinese herbal decoction activates the phosphorylations of extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF-7 cells.

Danggui buxue tang (DBT), a Chinese herbal decoction used to treat ailments in women, contains radix Astragali (Huangqi; RA) and radix Angelicae Sinensis (Danggui; RAS). The weight ratio of RA to RAS used in DBT must be 5:1 as stipulated as early as AD 1247; however, DBT's mechanism of action has never been described. Here, the estrogenic effects of DBT were investigated by determining the phosphorylations of estrogen receptor alpha (ER alpha) and extracellular signal-regulated kinase 1/2 (Erk1/2) in cultured MCF-7 cells. The application of DBT triggered the phosphorylation of ER alpha and Erk1/2 in a time-dependent manner. In contrast to the effect of estrogen, DBT triggered ER alpha phosphorylation at both S118 and S167. This DBT-specific phosphorylation was not triggered by an extract of one of the individual herbs, or by mixing the extracts of RA and RAS. DBT-induced downstream signals are described here. These signals suggest the uniqueness of this Chinese herbal decoction that requires a well-defined formulation.

A Chinese herbal decoction, Danggui Buxue Tang, prepared from Radix Astragali and Radix Angelicae Sinensis stimulates the immune responses.

Danggui Buxue Tang (DBT), a Chinese medicinal decoction that is used commonly for treating women's ailments, contains Radix Astragali and Radix Angelicae Sinensis. The ratio of Radix Astragali and Radix Angelicae Sinensis used in DBT should be 5 : 1 as described in China in 1247 A.D. In order to verify the efficacy of this ancient formulation in stimulating the immune responses, DBT prepared from different drug ratios was applied onto cultured T-lymphocytes and macrophages. In cultured T-lymphocytes, DBT induced markedly cell proliferation, secretion of interleukin-2 and phosphorylation of extracellular signal-regulated kinase. In addition, the phagocytosis of cultured macrophages was increased by DBT treatment. The immunomodulatory effects of DBT were revealed to be the strongest in the extract derived from the drug ratio of 5 : 1. The current results verified that the ancient formulation of DBT has been optimized in stimulating immune responses.

Chemical and biological assessment of a chinese herbal decoction containing Radix Astragali and Radix Angelicae Sinensis: Determination of drug ratio in having optimized properties.

Danggui Buxue Tang (DBT), a Chinese medicinal decoction that is commonly used as a dietary supplement in treating woman with menopausal irregularity, contains two herbs: Radix Astragali (Huangqi) and Radix Angelicae Sinensis (Danggui). The ratio of Radix Astragali and Radix Angelicae Sinensis used in DBT should be 5:1 as described in China in 1247 A.D.; however, the rationale of this formula has not been given. Here, the chemical and biological properties of DBT, prepared from different ratios of the drugs, were determined. Significantly, higher amounts of Radix Astragali-derived astragaloside IV, calycosin, and formononetin and Radix Angelicae Sinensis-derived ferulic acid were found in DBT with Radix Astragali and Radix Angelicae Sinensis in a 5:1 ratio. By using the biological effects of DBT in stimulating osteoblast proliferation, estrogen promoter activation, and anti-platelet aggregation activity, the drug ratio of 5:1 produced the best effects. In addition, the use of ethanol-treated Radix Angelicae Sinensis enhanced the efficacy of DBT, and the treatment further increased the solubilities of chemical constituents. By analyzing the correlation of chemical and biological results, several chemicals showed positive correlation with DBT-induced bioactivities. The current results support the ancient formulation of DBT, and the identified chemicals could serve as markers for quality control of DBT.

Molecular genetic and chemical assessment of Rhizoma Curcumae in China.

Rhizoma Curcumae (Ezhu) is a traditional Chinese medicine that has been used in removing blood stasis and alleviating pain for over a thousand years. Three species of Curcuma rhizomes are being used, which include Curcuma wenyujin, Curcuma phaeocaulis, and Curcuma kwangsiensis. In China, the production of Rhizoma Curcumae largely depends on agricultural farming. The essential oils are considered as active constituents in Rhizoma Curcumae, which include curdione, curcumol, and germacrone. On the basis of the yield of curdione, curcumol, and germacrone in an orthogonal array design, the optimized extraction condition was developed. The amounts of these compounds within essential oils in Rhizoma Curcumae varied according to different species and their regions of cultivation. Chemical fingerprints were generated from different species of Curcuma, which therefore could serve as identification markers. In molecular genetic identification of Rhizoma Curcumae, the 5S-rRNA spacer domains of 5 Curcuma species, including the common adulterants of this herb, were amplified, and their nucleotide sequences were determined. Diversity in DNA sequences among various species was found in their 5S-rRNA spacer domains. Thus, the chemical fingerprint together with the genetic distinction could serve as markers for quality control of Curcuma species.

Chemical and biological assessment of a traditional chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis: orthogonal array design to optimize the extraction of chemical constituents.

Danggui Buxue Tang (DBT) is a simple decoction, having about 800 years of usage in China to treat menopausal irregularity in women, which contains two herbs: Radix Astragali (Huangqi) and Radix Angelicae Sinensis (Danggui). Traditionally, boiling water has been used for preparing DBT; however, the optimized conditions of extraction have not yet been determined. Here, the amounts of Radix Astragali-derived astragaloside IV, calycosin, formononetin, and Radix Angelicae Sinensis-derived ferulic acid and ligustilide were determined in DBT, which were extracted according to an orthogonal array experimental design having three variable parameters: extraction time, extraction volume and number of repeats of the extraction. Our results suggest that extraction time and number of repeats of the extraction are two crucial factors, while extraction volume is a subordinate factor. The optimized conditions for extraction were therefore established. Besides the chemical composition, the estrogenic and anti-platelet aggregation activities of DBT were determined in different groups of the extraction, and the results of bioassays were in line with the amounts of the analyzed chemical ingredients. The results provide a model system for establishing the quality assurance of the herbal preparation.

A polysaccharide isolated from Cordyceps sinensis, a traditional Chinese medicine, protects PC12 cells against hydrogen peroxide-induced injury.

Cordyceps sinensis, a well-known traditional Chinese medicine, possesses activities in anti-tumour, anti-oxidation and stimulating the immune system; however, the identity of active component(s) is not determined. By using anti-oxidation activity-guided fractionation, a polysaccharide of molecular weight approximately 210 kDa was isolated from cultured Cordyceps mycelia by ion-exchange and sizing chromatography. The isolated polysaccharide, having strong anti-oxidation activity, contains glucose, mannose and galactose in a ratio of 1 : 0.6 : 0.75. The pre-treatment of isolated polysaccharide on the cultured rat pheochromocytoma PC12 cells shows strong protective effect against hydrogen peroxide (H(2)O(2))-induced insult. Treatment of the cells with the isolated polysaccharide at 100 microg/ml prior to H(2)O(2) exposure significantly elevated the survival of PC12 cells in culture by over 60%. In parallel, the H(2)O(2)-induced production of malondialdehyde in cultured cells was markedly reduced by the polysaccharide treatment. Moreover, the pre-treatment of the isolated polysaccharide significantly attenuated the changes of glutathione peroxidase and superoxide dismutase activities in H(2)O(2)-treated cells in a dose-dependent manner. This is the first report in identifying a polysaccharide from Cordyceps, which protects against the free radical-induced neuronal cell toxicity.

Molecular genetic and chemical assessment of radix Angelica (Danggui) in China.

The roots of Angelica sinensis (Danggui), a traditional Chinese medicine, have been used for invigorating blood circulation for over 2000 years in China. Three common species of Angelica roots are found in Asia: A. sinensis from China, A. acutiloba from Japan, and A. gigas from Korea. By using a molecular genetic approach, the 5S-rRNA spacer domains of the three species of Angelica were amplified, and their nucleotide sequences were determined. Diversity in DNA sequences among various species was found in their 5S-rRNA spacer domains, which could serve as markers for authentic identification of Angelica roots. In chemical analyses, the main constituents of Angelica roots including ferulic acid and Z-ligustilide were determined by HPLC; roots of A. sinensis were clearly distinct in that they contained approximately 10-fold higher levels of ferulic acid and Z-ligustilide as compared to roots of A. acutiloba and A. gigas. In addition, the amounts of main constituents in roots of A. sinensis varied according to different regions of cultivation and different methods of preservation. The chemical profile determined by HPLC therefore could serve as a fingerprint for quality control of Angelica roots.

Chemical assessment of roots of Panax notoginseng in China: regional and seasonal variations in its active constituents.

Root of Panax notoginseng (Radix Notoginseng, Sanqi) is a well-known traditional Chinese medicine and is mainly cultivated in Wenshan of Yunnan, China. The active constituents include saponin, dencichine, flavonoid, and polysaccharide; however, the levels of these components vary in different geographical regions of growth and also show a seasonal variation. By using high-performance liquid chromatography and spectrophotometry, the contents of notoginsenoside R1, ginsenoside R(g1), R(b1), R(d), dencichine, flavonoid, and polysaccharide were determined and compared with Radix Notoginseng collected from different regions of growth in China, as well as from different seasons of harvest and market grades. Using the contents of these active constituents as markers, the best quality of Radix Notoginseng is found in the southwestern parts of Wenshan, and the best season for the harvest is September to October. In addition, the unseeded plants produced a better quality of Radix Notoginseng. The current results provide useful information for the quality control of Radix Notoginseng and its further development in establishing the good agriculture practice standard of P. notoginseng in China.