[European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union（EU）, and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development.

Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial.

BACKGROUND: Hawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release. METHODS: We used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period. RESULTS: Twenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications. CONCLUSION: We found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism. TRIAL REGISTRATION: This trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: NCT01331486.

Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards.

Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. Although recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn are largely a consequence of the lack of availability of authentic standards that would allow for the directed development and validation of expedient analytical methodologies. In this study, we developed a method for the analysis of structurally related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally related (-)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (-)-epicatechin-3'-ß-D-glucuronide, (-)-epicatechin-3'-sulfate, and a 3'-O-methyl-(-)-epicatechin-5/7-sulfate are the predominant SREM in humans and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the previously reported discrepancies regarding flavanol metabolism, consisting, to a significant extent, of interlaboratory differences in sample preparation (enzymatic treatment and sample conditioning for HPLC analysis) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic.

Development of a potential reference material for evaluating antioxidant activity.

Phenolic phytochemical are known to perform several functions ranging from phytoprotectants, to protecting lipids in food products, to antioxidant activity in animals and humans. The need for a common standard mixture containing multiple phenolic phytochemicals is critical for the development of a robust validation assay for accurately quantifying antioxidant activity in various matrixes. Different research groups have used A wide array of single purified reference phenolic compounds in this regard. A 5 compound mixture (caffeic acid, morin hydrate, hesperetin, catechin hydrate, and epigallocatechin gallate) containing phenolic compounds from 4 subgroups (phenolic acid, flavone, flavanone, and flavan-3-ol) was prepared. The mixture was assayed for stability evaluation by high-performance liquid chromatography (HPLC) using a diode array detection procedure for a 3 month time interval. HPLC analysis confirmed that there was no significant interaction between different components of the mixture. The among-sample relative standard deviation (RSD) of all 5 phenolic compounds, as well as the total HPLC area, was < 1%. The RSD due to instrument variation was < 2% and the total RSD among-days was < 5%. These results unambiguously suggest that the sample was stable for a 3 month time interval in an amber vial stored in a refrigerator below 5 degrees C. This mixture is currently being used for the single-laboratory validation study for the assay of total phenolic content by the Folin-Ciocalteu method and the antioxidant capacity by oxygen radical absorbing capacity procedure.