Chun-Feng Qiao

Chemical markers for the quality control of herbal medicines: an overview.

Selection of chemical markers is crucial for the quality control of herbal medicines, including authentication of genuine species, harvesting the best quality raw materials, evaluation of post-harvesting handling, assessment of intermediates and finished products, and detection of harmful or toxic ingredients. Ideal chemical markers should be the therapeutic components of herbal medicines. However, for most herbal medicines, the therapeutic components have not been fully elucidated or easily monitored. Bioactive, characteristic, main, synergistic, correlative, toxic and general components may be selected. This article reviews the effective use of chemical markers in the quality control of herbal medicines including the selection criteria considering the roles and physicochemical factors which may affect the effective use of chemical markers.

Chemical profiling of Radix Paeoniae evaluated by ultra-performance liquid chromatography/photo-diode-array/quadrupole time-of-flight mass spectrometry.

In this study, an ultra-performance liquid chromatography/photo-diode-array/quadrupole time-of-flight mass spectrometry (UPLC-PDA-QTOFMS) based chemical profiling method was established for rapid global quality evaluation of Radix Paeoniae. By virtue of the high resolution, high speed of UPLC and the accurate mass measurement of TOFMS, a total of 40 components including 29 monoterpene glycosides, 8 galloyl glucoses and 3 phenolic compounds were simultaneously separated within 12min, and identified through the matching of empirical molecular formulae with those of published components in the in-house library, and were further elucidated by adjusted lower energy collision-induced dissociation (CID) mass spectra. Among forty components, five monoterpene glycoside sulfonates were identified as novel components. The established method was successfully applied to rapidly and globally compare the quality of Radix Paeoniae Alba and Radix Paeoniae Rubra, two post-harvesting handled products of Radix Paeoniae. Together with paeoniflorin sulfonate, five newly assigned monoterpene glycoside sulfonates were characteristic markers to detect non-official sulfur dioxide gas fumigated Radix Paeoniae Alba samples. It could be concluded that UPLC-PDA-QTOFMS based chemical profiling is a powerful approach for the global quality evaluation of Radix Paeoniae as well as other herbal medicines.

Decocting-induced chemical transformations and global quality of Du–Shen–Tang, the decoction of ginseng evaluated by UPLC–Q-TOF-MS/MS based chemical profiling approach

An UPLC-Q-TOF-MS/MS based chemical profiling method was developed to evaluate decocting-induced chemical transformations in Du-Shen-Tang, the decoction of the root of Panax ginseng. Under the optimized UPLC and Q-TOF-MS/MS conditions, over 50 peaks were separated and detected in Du-Shen-Tang within 18 min. The components were identified by comparing the mass spectra and retention time with that of reference compounds, and/or tentatively assigned by elucidating low energy CID fragment ions as well as matching empirical molecular formula with that of the published known compounds. Totally 45 major ginsenosides were identified in Du-Shen-Tang, 21 of which were determined to be newly generated during the decoction of ginseng. The mechanisms involved were further deduced to be hydrolysis, dehydration, decarboxylation and addition reactions of the original ginsenosides in white ginseng through analyzing mimic decoctions of 13 pure reference ginsenosides. Significant difference in chemical profiles between decoctions of two batches of white ginseng suggested that storage duration or other factors significantly influenced the quality consistency of not only the crude drug but also the decoction (Du-Shen-Tang) of white ginseng.

Xanthones with growth inhibition against HeLa cells from Garcinia xipshuanbannaensis.

Eight prenylated xanthones, bannaxanthones A-H (1-8), together with seven known compounds, were isolated from the acetone extract of the twigs of Garcinia xipshuanbannaensis. Their structures were elucidated by spectroscopic data interpretation. The cytotoxic activities of these compounds were evaluated using the MTT method. The results showed that xanthones with an unsaturated prenyl group had stronger cytotoxic activity against cancer cells, whereas those with hydroxylated prenyl groups had none.

Cytotoxic Acylphloroglucinol Derivatives from the Twigs of Garcinia cowa

An unusual polyprenylated acylphloroglucinol derivative unsubstituted at C-2 and C-6, garcicowin A (1), together with three other new (garcicowins B-D, 2-4) and nine known analogues, was isolated and characterized from the twigs of Garcinia cowa. The structures of 1-4 were elucidated by interpretation of their spectroscopic data. The compounds isolated were evaluated for their cytotoxicity against two cancer cell lines (HT-29 and HCT116) and against normal colon cells (CCD-18Co), and the results demonstrated their selective toxicity toward the cancer cells.

Cytotoxic Polyprenylated Xanthones from the Resin of Garcinia hanburyi

Thirteen xanthones (1-13) were isolated from the resin of Garcinia hanburyi. Among them, two new compounds (namely gaudichaudic acid, and isogambogenic acid, 1, 2), and one new natural product (deoxygaudichaudione A, 3) were identified on the basis of extensive spectral evidence including detailed 2D NMR data. Ten of these xanthones were tested for their cytotoxicities against human leukemia K562 (K562/S) and doxorubicin-resistant K562 (K562/R) cell lines, and showed similar inhibitory effects on both cell lines, suggesting that this group of polyprenylated xanthones might not be multidrug resistance (MDR) substrates.

An experimental design approach using response surface techniques to obtain optimal liquid chromatography and mass spectrometry conditions to determine the alkaloids in Meconopsi species

A statistic approach using response surface methodology (RSM) for optimization of the ultra-high performance liquid chromatography (UHPLC) gradient and ionization response of electrospray ionization mass spectrometry (ESI-MS) to analyze the main alkaloids from the plant matrices of six Meconopsi species is presented. The optimization was performed with Box-Behnken designs (BBD) and the multicriteria response variables were described using global Derringers desirability. Four parameters of UHPLC and six major parameters of ESI-MS were investigated for their contribution to analytes separation and response, leading to a total of 27 and 54 experiments being performed for each instrument, respectively. Quantitative analysis of four main alkaloids in nine samples from six Meconopsis species was employed to evaluate the statistical significance of the parameters on UHPLC-QTOF/ESI-MS analytes response. The results indicated that the optimized UHPLC-QTOF-MS method is very sensitive with the limit of detections (LODs) ranging from 0.5 to 0.1 ng/ml. The overall intra-day and the inter-day variations were less than 2.45%. The recovery of the method was in the range of 94.3-104.8% with RSD less than 4.0%. This approach has important implication in sensitivity enhancement of the ultra-trace determination of alkaloids from complex matrixes in the fields of natural products, metabolomics and pharmacokinetics.

Bioassay-Guided Isolation of Xanthones and Polycyclic Prenylated Acylphloroglucinols from Garcinia oblongifolia

Bioassay-guided fractionation of the acetone extract of the bark of Garcinia oblongifolia has resulted in the isolation of three new xanthones, oblongixanthones A-C (1-3), three new polyprenylated benzoylphloroglucinols, oblongifolins E-G (4-6), and 12 known compounds. Oblongifolins I (5) and J (6) are the first natural products that have similar structural features to those of two known oxidation products of garcinol. The structures of the new compounds 1-6 were characterized by spectroscopic data interpretation. All isolates were assayed for their apoptosis-inducing effects against HeLa-C3 cells. Oblongifolin C (16) was found to be the most potent apoptotic inducer of the compounds evaluated.

Qualitative and quantitative analysis of diterpenoids in Salvia species by liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

An on-line ultra-high-performance liquid chromatography (UHPLC) coupled with photodiode-array detection and quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) method has been optimized and established for the qualitative and quantitative analysis of the important diterpenoids in the methanol extracts of 12 Salvia species. Specific marker components were identified for the classification of the Salvia samples by principal component analysis. The accurate mass measurement within 3 ppm error for all the protonated molecules and subsequent fragment ions offers higher quality structural information for interpretation of fragmentation pathways of various groups of diterpenoids. Thus, a total of 21 diterpenoids from different Salvia species were separated within 10 min, and were unequivocally or tentatively identified via comparisons with authentic standards and literature. This UHPLC-QTOF-MS/MS method was validated to be sensitive, precise and accurate with the limit of detections at 3.0-16 ng/ml, and the overall intra-day and the inter-day variations less than 3%. The recovery of the method was in the range of 96.2-101.8%, with relative standard deviation (RSD) less than 3.0%. The results demonstrated that the qualitative and quantitative differences in diterpenoids were not only useful for chemotaxonomy in some Salvia species but also for the standardization and differentiation of large numbers of similar samples.

Antidepressant-like effects of psoralidin isolated from the seeds of Psoralea Corylifolia in the forced swimming test in mice.

The antidepressant-like effects of psoralidin isolated from the seeds of Psoralea corylifolia were investigated in the forced swimming test (FST) in ICR strain of male mice. Psoralidin significantly decreased immobility time and increased swimming behavior without altering climbing behavior in the mouse FST after oral administration for 1 h or 3 consecutive days. Psoralidin did not affect locomotor activity in the open-field test. After a 3-day treatment, psoralidin significantly increased 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in various brain regions, as well as, changed dopamine (DA) levels in striatum in mice exposed to FST. Psoralidin also ameliorated the elevations in serum corticotropin-releasing factor (CRF), adrenal corticotropin-releasing hormone (ACTH) and corticosterone concentrations induced by swimming stress in mice. These results suggested that psoralidin possessed potent antidepressant-like properties that were mediated via the monoamine neurotransmitter and the hypothalamic-pituitary-adrenal (HPA) axis systems.