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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., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Angelica Sinensis Radix (roots of Angelica sinensis; ASR) is a popular herbal supplement in China for promoting blood circulation. Today, sulfur-fumigation is commonly used to treat ASR as a means of pest control; however, the studies of sulfur-fumigation on the safety and efficacy of ASR are very limited. Here, we elucidated the destructive roles of sulfur-fumigation on ASR by chemical and biological assessments. After sulfur-fumigation, the chemicals in ASR were significantly lost. The biological activities of anti-platelet aggregation, induction of NO production and estrogenic properties were compared between the water extracts of non-fumigated and sulfur-fumigated ASR. In all cases, the sulfur-fumigation significantly reduced the biological properties of ASR. In addition, application of water extract deriving from sulfur-fumigated ASR showed toxicity to cultured MCF-7 cells. In order to ensure the safety and to achieve the best therapeutic effect, it is recommended that sulfur-fumigation is an unacceptable approach for processing herbal materials., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: Danggui Buxue Tang (DBT), a Chinese herbal decoction commonly used in treating women׳s ailments, contains two herbs: Angelica Sinensis Radix (ASR) and Astragali Radix (AR). Traditionally, ASR had to be pre-treated with yellow wine before the herbal preparation, which reduced the amount of volatile oil in water extract of ASR and DBT, and meanwhile the volatile oil-reduced DBT processed better bioactivities in cell cultures. The present study aimed to investigate the effect of volatile oil from ASR (Angelica oil) on the solubility of AR-derived ingredients and the biological properties of DBT., Materials and Methods: To standardize Angelica oil, four marker chemicals in ASR were determined by GC-QQQ-MS/MS. Subsequently, fifteen gram of AR was boiled with different amounts of Angelica oil. The amounts of astragaloside IV, calycosin, formononetin, total polysaccharides, total saponins and total flavonoids, all derived from AR, were extracted and determined by HPLC-UV/ELSD. To reveal the effect of Angelica oil on DBT functions, several cell assays related to the traditional functions of DBT were selected, including anti-platelet aggregation, induction of NO production, hematopoetic, estrogenic and osteogenic properties., Results: The inclusion of Angelica oil in AR during preparation significantly decreased the amount of AR-derived astragaloside IV, calycosin, formononetin, total saponins and total flavonoids in the final water extract. In parallel, an inclusion of Angelica oil caused a decrease of DBT׳s estrogenic and hematopoetic activities in cultured cells. Moreover, the Angelica oil decreased DBT-induced cell proliferation of cultured MG-63 and endothelial cells., Conclusions: The results indicated that Angelica oil was a negative regulator for DBT chemically and biologically, which supported the traditional practice of preparing DBT by using the wine-treated ASR., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Astragali Radix (AR) has been used for over 2000 years in China for the enrichment of "Qi". Hedysari Radix (HR), a herb having similar chemical composition with AR, has been commonly used as a substitute of AR in herbal decoction. In order to evaluate the possible replacement of HR for AR in Chinese herbal decoction, systematic comparison of AR and HR was done by chemical and biological assessments. The water extract of AR contained higher levels of calycosin, calycosin-glucoside, ononin, astragaloside III and astragaloside IV, while higher amount of formononetin was found in the HR extract. The estrogenic, erythropoetic and osteogenic effects were compared between the water extracts of AR and HR, and in all cases AR extract showed higher biological activities. Danggui Buxue Tang (DBT) is a very common herbal decoction for woman aliment, and which contains AR and Angelica Sinensis Radix. Here, we generated two forms of DBT having either AR or HR as the major herbs. Chemically, AR-contained DBT showed higher amounts of various active chemicals, except formononetin that was higher in HR-contained DBT. In parallel, the estrogenic, osteogenic and erythropoetic effects of DBT containing AR showed better activities than that of DBT having HR. Thus, AR and HR showed distinct differences in terms of chemical and biological properties. In order to achieve the best therapeutical effect, as well as to guarantee the safety, AR is recommended here to be used for making DBT., (Copyright © 2013. Published by Elsevier GmbH.)

Si Wu Tang (Four Agents Decoction), a traditional Chinese decoction composed of Angelica Sinensis Radix, Chuanxiong Rhizoma, Paeoniae Radix Alba, and Rehmanniae Radix Praeparata in a ratio of 1 : 1 : 1 : 1, has been used to treat women's diseases for more than a thousand years. According to the original description of Si Wu Tang, Angelica Sinensis Radix should be treated with wine. However, the importance of this wine-treated Angelica Sinensis Radix in Si Wu Tang's function has not been identified. In this article, the chemical and biological properties of two decoctions processed in different ways (Si Wu Tang with crude Angelica Sinensis Radix and Si Wu Tang with wine-treated Angelica Sinensis Radix) were compared for examination. The herbal decoction Si Wu Tang prepared from wine-treated Angelica Sinensis Radix contained much different amounts of its active compounds. Compared with Si Wu Tang using crude Angelica Sinensis Radix, Si Wu Tang prepared from wine-treated Angelica Sinensis Radix had better biological responses. Therefore, these findings accentuate the functional importance of herbs treated with wine in the Chinese decoction., (Georg Thieme Verlag KG Stuttgart · New York.)

The roots of Angelica sinensis [Angelica Sinensis Radix (ASR)] have been used as a common health food supplement for women's care for thousands of years in China. According to Asian tradition, ASR could be processed with the treatment of wine, which subsequently promoted the biological functions of ASR. By chemical and biological assessments, an orthogonal array design was employed here to determine the roles of three variable parameters in the processing of ASR, including oven temperature, baking time, and flipping frequency. The results suggested that oven temperature and baking time were two significant factors, while flipping frequency was a subordinate factor. The optimized condition of processing with wine therefore was considered to be heating in an oven at 80 °C for 90 min with flipping twice per hour. Under the optimized processing conditions, the solubilities of ferulic acid and Z-ligustilide from ASR were markedly increased and decreased, respectively. In parallel, the biological functions of processed ASR were enhanced in both anti-platelet aggregation and estrogenic activation; these increased functions could be a result of the altered levels of ferulic acid and Z-ligustilide in wine-processed ASR. Thus, the chemical and biological assessment of the processed ASR was in full accordance with the Chinese old tradition.

Fo Shou San (FSS) is an ancient herbal decoction comprised of Rhizoma Chuanxiong (RC; Chuanxiong) and Radix Angelicae Sinensis (RAS; Danggui) in a ratio of 2 : 3. It is mainly prescribed for patients having a blood deficiency. This combination is considered the most popular herb pair among Chinese medicines; however, the rationale of having these two chemically similar herbs within the decoction has historically not been made clear. Here, we attempted to reveal the chemical and biological properties of this decoction as a means to deduce its mechanism of action. The effects of FSS were determined in different cell culture models. With respect to stimulation of blood circulation, FSS inhibited ADP-mediated platelet aggregation in a dose-dependent manner. In order to reveal the hematopoietic effect of this decoction, FSS was applied onto cultured K562 human leukemia cells and Hep3B human hepatocellular carcinoma cells. Application of FSS in cultured K562 cells inhibited cell proliferation and subsequently induced the production of hemoglobin. Additionally, the mRNA expression of erythropoietin (EPO) was induced in a dose-dependent manner when FSS was applied to Hep3B cells. The current results reveal the effects of FSS in different cell models, paving a direction for mechanistic studies., (© Georg Thieme Verlag KG Stuttgart · New York.)

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., (Copyright Georg Thieme Verlag KG Stuttgart. New York.)

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.

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.