The Processing of Angelica Sinensis Radix with Wine According to Ancient Chinese Methodology: An Alternation of Chemical Composition and Biological Function

Herbal processing is a major feature of traditional Chinese medicine (TCM). Many Chinese herbs are subjected to specific treatments before they are used as drugs. According to TCM theory, herbal processing is to fulfill requirements of different therapies, dispensation and preparations. The main purpose of herbal processing is to decrease the toxicity and to maximize/ increase the efficacy. In China, the herbal processing has been developed for thousands of years and become indispensable for the herbal application. Of different processing methods, the treatment with wine is one of the widest used methods. For example, Angelica Sinensis Radix (ASR) is treated with wine before the application as herbal drugs. Here, we studied the wine-treatment of ASR as an example to reveal the importance of herbal processing in TCM application.;According to Chinese ancient usage, ASR should be treated with yellow wine, i.e. a heated-pan was used to fry ASR with yellow wine. However, this traditional method could not control the temperature, which was not conducive for quality assurance. By chemical and biological assessments, oven-baking was applied here to determine the roles of three variable parameters in the processing of ASR, including oven temperature, baking time and flipping frequency. The optimized condition of processing with wine was considered to be heating in an oven at 80 °C for 90 min with flipping twice per hour.;After wine-treatment, many chemical constituents in ASR were changed significantly. The content of ferulic acid increased while that of Z-ligustilide decreased in the extract from wine-treated ASR. Total volatile oils, a major part in ASR, were over 30% decreased by the treatment with wine. Besides, the biological functions of wine-treated ASR were significantly enhanced. The results showed that the wine-treatment increased the circulatory functions of ASR via inhibiting platelet aggregation and stimulating NO production in cultured HUVEC cells. Moreover, the estrogenic-like activity of the wine-treated ASR in cultured MCF-7 cells was markedly enhanced. By revealing the molecular mechanism, the effect of wine-treated ASR on NO production was shown to be mediated by the phosphorylation of eNOS in cultured HUVECs. Similarly, the estrogenic activity of the wine-treated ASR was robust in the phosphorylation of ERa at S118 and of Erk1/2 in cultured MCF-7 cells. The increased properties of wine-treated ASR in both anti-platelet aggregation and estrogenic activation could be a result of the altered levels of ferulic acid and Z-ligustilide in the wine-treated ASR. These studies supported the traditional usage of the wine-treated ASR in TCM application, and which indeed showed better function in stimulating "blood".;Sulfur-smoked ASR is commonly found in the Chinese herbal market. Moreover, Aneglica Gigas Radix (AGR) is also being used in the markets of Southeast Asia as ASR. Here, the chemical compositions of different wine-treated Angelica roots were compared: a robust difference was found between ASR and AGR. In addition, the wine-treatment decreased the cytotoxicity of AGR and sulfur-smoked ASR against a variety of cultured cell lines. But the biological effects were more robustly increased in the wine-treated ASR, as compared to other types of Angelica roots.;The role of wine-treated ASR in herbal formulae, Danggui Buxue Tang (DBT), Huangqi Buqi Tang and Si Wu Tang, were elucidated. The wine-treatment of ASR altered the chemical constituents and biological properties related to "blood" of these herbal decoctions in different degrees. Furthermore, ASR-derived total volatile oils, decreased by the wine-treatment, had been demonstrated to be a negative regulator of DBT's functions. These results supported that the ancient wisdom of having the wine-treated ASR in herbal formulae.;In good agreement with the traditional usage, the current results strongly supported the rationale of treating ASR with wine: (i) a modern wine-treatment method of ASR was optimized chemically and biologically; (ii) the wine-treatment of ASR was proved to be reasonable, which should be complied with today; (iii) the determined relationships, between the chemical and biological changes, could further explain the underlying mechanism of the role of wine-treatment in ASR and in herbal formulae. By using chemical and biological assessment, a systematic approach for wine-treatment of ASR was developed here: these methodologies could be applied in other herbal processing methods.