Abstract

BackgroundMicrobial fermentation has been widely applied in traditional Chinese medicine (TCM) for thousands of years in China. Various beneficial effects of fermentation for applications in TCM or herbals have been reported, such as enhanced anti-ovarian cancer, antioxidative activity, and neuroprotective effects. Ge-Gen-Qin-Lian decoction (GQD), a classic TCM formula, has been used to treat type 2 diabetes mellitus in China. In this study, GQD was fermented with Saccharomyces cerevisiae, and the antidiabetic activities and overall chemical profiles of raw and fermented GQD (FGQD) were systematically compared.MethodsFirst, the antidiabetic effects of GQD and FGQD on high-fat diet and streptozotocin (STZ)-induced diabetic rats were compared. Then, high-performance liquid chromatography Q Exactive MS was applied for rapid characterization of the chemical components of GQD. Additionally, we proposed an integrated chromatographic technique based untargeted metabolomics identifying differential chemical markers between GQD and FGQD and targeted analysis determining the fermenting-induced quantitative variation tendencies of chemical marker strategy for overall chemical profiling of raw and fermented GQD.ResultsBoth GQD and FGQD displayed effects against HFD and STZ-induced diabetes, and FGQD showed a better recovery trend associated with profound changes in the serum lipoprotein profile and body weight gain. In addition, 133 compounds were characterized from GQD. It was demonstrated that the integrated strategy holistically illuminated 30 chemical markers contributed to the separation of GQD and FGQD, and further elucidated the fermenting-induced chemical transformation mechanisms and inherent chemical connections of secondary metabolites. Although there were no new secondary metabolites in FGQD compared with GQD, the amounts of secondary metabolites, which were mostly deglycosylated, were redistributed in FGQD.ConclusionThe anti-diabetic activities of GQD could be improved by applying fermentation technology. Moreover, the proposed strategy could serve as a powerful tool for systematically exploring the chemical profiles of raw and fermented formulas.

Highlights

  • Microbial fermentation has been widely applied in traditional Chinese medicine (TCM) for thousands of years in China

  • No significant difference was observed among the drug-treated groups (p > 0.05), the diabetic rats in fermented GQD (FGQD) showed a better trend of recovery

  • The treatments with metformin hydrochloride (HM) and FGQD reversed the up-regulation of LDL and down-regulation of HDL in the diabetics rats group to the control level, whereas no significant (p > 0.05) effect was observed for Gen-Qin-Lian decoction (GQD) (Fig. 2)

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Summary

Introduction

Microbial fermentation has been widely applied in traditional Chinese medicine (TCM) for thousands of years in China. Fermented medicinal plants and traditional herbal medicine have been shown to exhibit enhanced antiovarian cancer activity, antioxidative activity, and neuroprotective effects compared to the raw formulas [6,7,8,9]. Various beneficial effects of fermentation applied to TCM or medicinal plants have been reported, systematic comparisons of the pharmacological actions and overall chemical profiles of raw and fermented TCM formulas are scarce. Liquid chromatography coupled with mass spectrometry (LC–MS)-based untargeted metabolomic approach can provide global profiles of abundant (up to hundreds of ) secondary metabolites by determining their presence, amount and occasionally their structures [14, 15] and has been successfully used to study the effects of processing on herbal drugs, such as Rehmanniae Radix and Fructus corni [15, 16]

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