Effect of the vinegar-process on chemical compositions and biological activities of Euphorbia kansui: A review.

ETHNOPHARMACOLOGICAL RELEVANCE:In traditional Chinese medicine (TCM) the root of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), is used for treating edema and ascites but is also of toxicological concerns. And the clinical applications of EK have been seriously restricted for its severe toxicity. To reduce its toxicity, a commonly used clinical practice is processing it with vinegar.

AIM OF THE REVIEW:This review aimed to summarize and discuss updated information on biological activities and phytochemistry of EK before and after vinegar-processing, and provide feasible insights for further research on the chemical composition, toxicity and pharmacological effects of EK before and after vinegar-processing.

MATERIALS AND METHODS:The relevant information on chemical compositions and biological activities of EK before and after vinegar-processing was collected from scientific databases (Google Scholar, PubMed, CNKI, SpringerLink, Web of Science, Wiley Online Library and SciFinder). Additionally, published and unpublished Ph.D. and MSc. dissertations were also obtained from online databases.

RESULTS AND DISCUSSIONS:Diuretic and purgative effect of EK are well documented pharmacologically as are acute, irritant and organic toxic effects.?Some of about terpenoids reported have antiproliferative effects on cancer cells and potential antiviral effect. After processing with vinegar, the contents of terpenoids mostly were reduced (ingenane and jatrophane type) with some new compounds being generated (unclear).?Also, the toxicity of EK was decreased (using mice, rats and zebrafish embryos model), while the diuretic and purgative effects were retained (using cancerous ascites model rats and mice).

CONCLUSIONS:While some evidence exists for the reduction of toxicity without compromising the pharmacological effects of EK after vinegar processing, the specific mechanism of action remains unknown. Consequently, further research is necessary to investigate the mechanisms and the relationship between vinegar processing and changes in the chemical composition as well as pharmacological effects/toxicity. This is essential before a safe clinical use can be endorsed.

A metabolomics approach to study the dual modulation by characterization of chemical alteration during processing of Gardeniae Fructus using UPLC-ESI-QTOF?

Abstract

Dual modulation is an interesting phenomenon that may occur during Chinese Materia Medica (CMM) processing whereby the crude and processed products have completely opposite therapeutic effects?in vivo?due to chemical component alteration. Therefore, a comprehensive study of the chemical alteration in order to shed light on the reason behind dual modulation is of critical importance. Metabolomics employs an untargeted approach to obtain an overview on secondary metabolites in multi-component systems using high resolution LC-MS2, which fulfills the requirement of a comprehensive analysis to clarify the mechanism of dual modulation. Gardeniae Fructus (GF), is one of the many widely used medicines across Asia, and its processed product exhibits completely opposite therapeutic effects on blood stasis. Therefore, we chose crude and processed GF to examine changes in secondary metabolites using UPLC-ESI-QTOF. In the subsequent chemometric analysis, both principal component analysis (PCA, unsupervised feature extraction) and orthogonal partial least-squares analysis (OPLSA, supervised feature extraction) were used to find out the chemical changes during processing. Iridoid Glycosides – jaminoside B, genipine-1-β-gentiobioside, 6α-hydroxygeniposide, and geniposide?– and other ingredients such as mannitol and crocin were found to have decreased three to four fold in processed GF compared to crude GF, whereas another iridoid glycoside?with a carboxyl group, mussaenosidic acid, was found to increase two fold in the processed product. This rapid yet reliable screening method can be also applied to other CMM to characterize the chemical changes and further explain the reasons behind dual modulation.

Toxicity Reduction of?Euphorbia kansui?Stir-Fried with Vinegar Based on Conversion of 3-O-(2′E,4′Z-Decadi-enoyl)-20-O-acetylingenol

Abstract

The dried roots of?Euphorbia kansui?S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by?Euphorbia kansui?(EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated.?Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing.?This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.

Keywords:?Euphorbia kansui