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Oplopanax elatus (Nakai) Nakai is an oriental herb, the polyyne-enriched fraction of which (PEFO) showed anticolorectal cancer (anti-CRC) effects. Other concomitant components, which are inevitably bio-transformed by gut microbiota after oral administration, might be interfere with the pharmacodynamics of polyynes. However, the influence of human gut microbiota on molecules from O. elatus possessing anticancer activity are yet unknown. In this study, the compounds in PEFO and PEFO incubated with human gut microbiota were analyzed and tentatively identified by HPLC-DAD-QTOF-MS. Two main polyynes ((3$S,$8$S)$-falcarindiol and oplopandiol) were not significantly decomposed, but some new unknown molecules were discovered during incubation. However, the antiproliferative effects of PEFO incubated with human gut microbiota for 72 h (PEFO I) were much lower than that of PEFO on HCT-116, SW-480, and HT-29 cells. Furthermore, PEFO possessed better anti-CRC activity in vivo, and significantly induced apoptosis of the CRC cells, which was associated with activation of caspase-3 according to the Western-blot results ($P<0.05$). These results suggest anticolorectal cancer activity of polyynes might be antagonized by some bio-converted metabolites after incubation with human gut microbiota. Therefore, it might be better for CRC prevention if the polyynes could be orally administrated as purified compounds.

In Chinese medicine, fermentation is a highly important processing technology whereby medicinal herbs are fermented under appropriate temperature, humidity, and moisture conditions by means of the action of microorganisms to enhance their original characteristics and/or produce new effects. This expands the scope of such medicines and helps them to meet the stringent demands of clinical application. Since ancient times, Chinese medicine has been made into Yaoqu to reduce its toxicity and increase its efficiency. Modern fermentation technologies have been developed on the basis of traditional fermentation techniques and modern biological technology, and they can be divided into solid fermentation, liquid fermentation, and two-way fermentation technologies according to the fermentation form employed. This review serves as an introduction to traditional fermentation technology and its related products, modern fermentation technologies, and the application of fermentation technology in the field of Chinese medicine. Several problems and challenges facing the field are also briefly discussed.

Fermentation is a processing method used in traditional Chinese medicine (TCM). However, traditional fermentation methods suffer from poor production control. In contrast, probiotic fermented herbal medicine (PFHM) offers advantages such as the use of pure strains, a controllable process, and the ability to produce a variety of active enzymes during fermentation. As a result, PFHM has become a research hotspot. This review focuses on the progress, challenges, and opportunities in the research of PFHM. The use of probiotic enzymes during fermentation alters the active ingredients of TCM, resulting in positive pharmacological effects such as increased active ingredients, reduced toxicity, new pharmacological effects, and the reuse of herbal residues. PFHM has the potential to transfer the metabolic transformation of the effective components of TCM by intestinal flora outside the body during production and preparation, which has a broad application prospect. However, due to the complexity of the chemical composition of TCM, the mechanism of PFHM requires further investigation. Finally, we discuss the prospects of industrializing PFHM, which is essential for promoting the innovation and modernization of TCM.

An active site model for generic hydroxylation of xenobiotes by the fungus Rhizopus oryzae ATCC 11145 has been developed. The model was constructed using data from known metabolites of R. oryzae, as reported in the chemical literature, including diterpenes and steroids. The model takes the form of an irregular polyhedron of 340 ų volume, with two hydrophilic patches and an active site region. It was validated using data for other known substrates, including terpenes, steroids, octalin, and hydrindenone derivatives, drawn from the literature. The interpretive and predictive abilities of the model are discussed.

Xenobiotics biotransformation in humans is a process of the chemical modifications, which may lead to the formation of toxic metabolites. The prediction of such metabolites is very important for drug development and ecotoxicology studies. We created the web-application MetaTox (http://way2drug.com/mg) for the generation of xenobiotics metabolic pathways in the human organism. For each generated metabolite, the estimations of the acute toxicity (based on GUSAR software prediction), organ-specific carcinogenicity and adverse effects (based on PASS software prediction) are performed. Generation of metabolites by MetaTox is based on the fragments datasets, which describe transformations of substrates structures to a metabolites structure. We added three new classes of biotransformation reactions: Dehydrogenation, Glutathionation, and Hydrolysis, and now metabolite generation for 15 most frequent classes of xenobiotic’s biotransformation reactions are available. MetaTox calculates the probability of formation of generated metabolite — it is the integrated assessment of the biotransformation reactions probabilities and their sites using the algorithm of PASS (http://way2drug.com/passonline). The prediction accuracy estimated by the leave-one-out cross-validation (LOO-CV) procedure calculated separately for the probabilities of biotransformation reactions and their sites is about 0.9 on the average for all reactions.