Pharmacokinetic evaluation of Sinisan containing vinegar-processed products in depressive rats, a comprehensive perspective of 'individual herb, herb-pair, and herbal formula'.

ETHNOPHARMACOLOGICAL RELEVANCE: As a classical formula for the treatment of depression, the clinical application of vinegar-processed products of Bupleuri Radix (Bupleurum chinense DC., BR) and Paeoniae Radix Alba (Paeonia lactiflora Pall., PRA) contained in Sinisan (SNS) is still controversial. AIM OF THE STUDY: Three levels of 'individual herb, herb-pair, and herbal formula' were employed to investigate whether and how the processing of main drugs affected the active constituents of pharmacokinetics in SNS, as well as their impacts on the hepatic CYP450 enzyme. MATERIALS AND METHODS: Rats were subjected to construct a chronic unpredictable mild stimulation (CUMS) model. A rapid and sensitive ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) analytical method was developed and validated for simultaneously quantitative evaluation of thirteen potential active compounds of SNS in depressive rat plasma, and successfully applied to a holistic comparison of pharmacokinetics. The differences in pharmacokinetic parameters based on three different forms of drug composition from BR and PRA before and after vinegar-processing were compared. Meanwhile, qRT-PCR and Western Blot were utilized to explore the metabolic activity of three isoforms of CYP450 enzyme scattered in the livers of depressive rats. RESULTS: The characteristic pharmacokinetics profiles of thirteen representative constituents in CUMS rats were influenced by vinegar-processing of BR and PRA and/or the compatibility. In detail, there were significant differences in the Cmax, AUC0-24, AUC0-∞, t1/2, and MRT0-24 of most constituents among the three different forms of drug composition from BR and PRA before and after vinegar-processing, with the most obvious changes in six constituents from the adjuvant and mediating guide drugs. And also, the pharmacokinetic parameters of seven constituents from BR and PRA in SNS containing vinegar-processed products obviously changed after compatibility. Additionally, the mRNA and protein levels of CYP1A2, CYP2E1, and CYP3A1 were observed to increase significantly with the processing of BR and PRA and the combination/formulation. CONCLUSIONS: In conclusion, SNS containing vinegar-processed products was more conducive to the absorption of most activated constituents compared to the original formula in vivo. The vinegar-processing of BR and PRA and the compatibility co-contribute to the pharmacokinetic variability of active compounds of SNS in CUMS rats, and the extent of contribution varies among drugs, which might be related to the regulation of the hepatic drug metabolizing enzymes. The finding of the investigation could help to better understand how active compounds metabolized in vivo, which might be helpful for guiding the clinical application of SNS containing vinegar-processed products.

Optimizing Processing Technology of Cornus officinalis: Based on Anti-Fibrotic Activity.

Cornus officinalis, a kind of edible herbal medicine, has been widely used in the protection of liver and kidney due to its medicinal and nutritional effect. Its anti-inflammatory, anti-tumor, and anti-oxidant activities can be enhanced by wine-steamed (WS) processing. Based on the activations of hepatic stellate cells-T6 (HSC-T6) and HK-2, our study used single-factor plus orthogonal design to investigate the anti-fibrosis of C. officinalis processed with steamed (S), high-pressure steamed (HPS), WS, high-pressure wine-steamed (HPWS), wine-dipped (WD), and wine-fried (WF). The chemical constituents in processed C. officinalis with higher anti-fibrotic activities were detected by ultra-high performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Results showed that C. officinalis with HPWS significantly inhibited the activations of HSC-T6 and HK-2. Moreover, compounds in C. officinalis with HPWS were obtained via UHPLC-Q-TOF-MS/MS, indicating that 27 components were changed compared with raw C. officinalis. These results demonstrated that HPWS is the optimal processing technology for anti-fibrosis of C. officinalis.

A Reasonable Evaluation of Chuanxiong Rhizoma Processing with Wine through Comparative Pharmacokinetic Study of Bioactive Components: Dominant Effect on Middle Cerebral Artery Occlusion Model Rats.

According to the ancient documents and Chinese herbal medicine processing experience, Chuanxiong Rhizoma was usually processed with yellow rice wine to improve efficacy. However, the relevant mechanisms are still unclear so far. In this study, a validated ultrahigh-performance liquid chromatography tandem mass spectrometry method was used to compare the pharmacokinetics of four representative components in middle cerebral artery occlusion rats after oral administration of raw and wine-processed Chuanxiong Rhizoma. The neurobehavioral scores and 2,3,5-triphenyltetrazolium chloride staining were employed to evaluate the model. Biological samples were prepared by protein precipitation with methanol. All analytes were separated on an ACQUITY BEH C18 column through gradient elution using acetonitrile and 0.01% of formic acid as mobile phase, and the flow rate was 0.3 mL/min. The results showed that the maximum plasma concentrations, the area values under the concentration-time curves of senkyunolide A, and ferulic acid in wine-processed Chuanxiong Rhizoma were all higher than in raw Chuanxiong Rhizoma, which were completely opposite to our previous studies in normal rats. Compared with normal rats, the theory that wine processing could enhance the efficacy of Chuanxiong Rhizoma may be better reflected in model rats.

Metabolomics Tools Assisting Classic Screening Methods in Discovering New Antibiotics from Mangrove Actinomycetia in Leizhou Peninsula.

Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program. In this study, an integrated strategy of combining phylogenetic data and bioactivity tests with a metabolomics-based dereplication approach was applied to fast track the selection process. A total of 521 actinomycetial strains affiliated to 40 genera in 23 families were isolated from 13 different mangrove soil samples by the culture-dependent method. A total of 179 strains affiliated to 40 different genera with a unique colony morphology were selected to evaluate antibacterial activity against 12 indicator bacteria. Of the 179 tested isolates, 47 showed activities against at least one of the tested pathogens. Analysis of 23 out of 47 active isolates using UPLC-HRMS-PCA revealed six outliers. Further analysis using the OPLS-DA model identified five compounds from two outliers contributing to the bioactivity against drug-sensitive A. baumannii. Molecular networking was used to determine the relationship of significant metabolites in six outliers and to find their potentially new congeners. Finally, two Streptomyces strains (M22, H37) producing potentially new compounds were rapidly prioritized on the basis of their distinct chemistry profiles, dereplication results, and antibacterial activities, as well as taxonomical information. Two new trioxacarcins with keto-reduced trioxacarcinose B, gutingimycin B (16) and trioxacarcin G (20), together with known gutingimycin (12), were isolated from the scale-up fermentation broth of Streptomyces sp. M22. Our study demonstrated that metabolomics tools could greatly assist classic antibiotic discovery methods in strain prioritization to improve efficiency in discovering novel antibiotics from those highly productive and rich diversity ecosystems.

[Roles of processing and compatibility in antidepression of Sini Powder:a metabonomics study].

The antidepressant mechanism of Sini Powder was investigated by metabonomics based on UHPLC-Q-TOF-MS, and the roles of processing and compatibility in the antidepression of Sini Powder were discussed in the present study. The chronic unpredictable mild stress(CUMS) model of depression was induced in the model group, the Bupleuri Radix group, the Paeoniae Radix Alba group, the herb-pair group(Bupleuri Radix-Paeoniae Radix Alba), the Sini Powder group, and the vinegar-processed Sini Powder group(Bupleuri Radix and Paeoniae Radix Alba were vinegar-processed). After the establishment of the model, the rats in each group were continuously administered with corresponding drugs(ig) at a dose of 9.6 g·kg~(-1) for eight days [the rats in the model group and the normal group(without model induction) received the same volume of normal saline at the same time]. Following the last administration, the differential metabolites were identified to analyze metabolic pathways based on the rat plasma samples collected from each group. A total of sixteen potential biomarkers were identified. The metabolites with significant changes were involved in many biological metabolic pathways, such as amino acid metabolism, pentose phosphate pathway, glycerol phospholipid metabolism, sphingolipid metabolism, and purine metabolism. After drug intervention, some biomarkers returned to normal levels. Further comparisons of processing and compatibility revealed that the vinegar-processed Sini Powder group had the most total metabolic pathways where differential metabolites were returned to normal. Compared with the individual herbs, the herb-pair significantly improved the recovery of differential metabolites in the pentose phosphate and purine metabolic pathways. Compared with the Sini Powder, the vinegar-processed Sini Powder facilitated the recovery of differential metabolites in the arginine biosynthesis, and pyrimidine and pentose phosphate metabolic pathways. As indicated by the results, Sini Powder may interfere with depression by regulating lipid and nucleotide metabolisms. The processing and compatibility of Chinese herbal medicines can potentiate the intervention on depression by regulating nucleotide, energy, and amino acid metabolisms to a certain extent.

Electroacupuncture Promoted Nerve Repair After Peripheral Nerve Injury by Regulating miR-1b and Its Target Brain-Derived Neurotrophic Factor.

Growing evidence indicates that electroacupuncture (EA) has a definite effect on the treatment of peripheral nerve injury (PNI), but its mechanism is not completely clear. MicroRNAs (miRNAs) are involved in the regulation of a variety of biological processes, and EA may enhance PNI repair by regulating miRNAs. In this study, the rat sciatic nerve injury model was treated with EA for 4 weeks. Acupoints Huantiao (GB30) and Zusanli (ST36) were stimulated by EA 20 min once a day, 6 days a week for 4 weeks. We found that EA treatment downregulated the expression of miR-1b in the local injured nerve. In vitro experiments showed that overexpression of miR-1b inhibited the expression of brain-derived neurotrophic factor (BDNF) in rat Schwann cell (SC) line, while BDNF knockdown inhibited the proliferation, migration, and promoted apoptosis of SCs. Subsequently, the rat model of sciatic nerve injury was treated by EA treatment and injection of agomir-1b or antagomir-1b. The nerve conduction velocity ratio (NCV), sciatic functional index (SFI), and S100 immunofluorescence staining were examined and showed that compared with the model group, NCV, SFI, proliferation of SC, and expression of BDNF in the injured nerves of rats treated with EA or EA + anti-miR-1b were elevated, while EA + miR-1b was reduced, indicating that EA promoted sciatic nerve function recovery and SC proliferation through downregulating miR-1b. To summarize, EA may promote the proliferation, migration of SC, and nerve repair after PNI by regulating miR-1b, which targets BDNF.

Astragalus polysaccharide alleviates cognitive impairment and ß-amyloid accumulation in APP/PS1 mice via Nrf2 pathway.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, and its etiology and pathogenesis are not fully understood. Astragalus polysaccharide (APS) has many pharmacological activities, but there are few reports about its role in AD. Using the common AD model APP/PS1 mice, it was found that the expression of Keap1 (a negative regulatory factor of Nrf2), the protein level of cytoplasmic Nrf2 and the content of MDA were increased significantly, while the mRNA level of Nrf2, the expression of Nrf2 in nucleus and the contents of SOD and GSH-Px were decreased significantly. APS treatment significantly increased the expression of Nrf2 in the nucleus but decreased its expression in the cytoplasm, and restored the expression levels of Keap1, SOD, GSH-Px and MDA. When APP/PS1 mice were treated with APS and injected with Nrf2 siRNA, the down-regulation of Nrf2 expression significantly blocked the regulation of APS on oxidative stress. Continuing to test the physiological function of AD mice showed that the spatial learning and memory abilities of APP/PS1 mice were impaired, the apoptosis of brain cells and the content of ß-amyloid (Aß) were significantly increased. APS treatment significantly improved the cognitive ability of APP/PS1 mice, reduced apoptosis and the accumulation of Aß, but the above effects of APS were blocked by Nrf2 siRNA injection. Therefore, APS can activate Nrf2 pathway to improve the physiological function of AD mice, which may have important clinical application value.

Analysis of endophytic and rhizosphere bacterial diversity and function in the endangered plant Paeonia ludlowii.

Paeonia ludlowii is indigenous to Tibet and has an important ecological and economic value in China. In Tibet, P. ludlowii has been used in folk medicine with relative success. Plant microbial endophytes play an important role in plant growth, health and ecological function. The diversity of endophytic bacteria associated with P. ludlowii remains poorly understood. In this study, the structure of the endophytic bacterial communities associated with different tissues, including fruits, flowers, leaves, stems, and roots, and rhizosphere soils was analyzed with Illumina MiSeq sequencing of bacterial 16S rDNA. A total of 426,240 sequences and 4847 operational taxonomic units (OTUs) were obtained. The OTUs abundance of roots was higher than that of other tissues; however, the OTUs abundance was similar among different deep soil samples. In the plant tissues, Cyanobacteria was the most abundant bacterial phylum, followed by Proteobacteria; however, the most abundant phyla were Proteobacteria and Acidobacteria in soil samples from three different layers. In addition, the diversity and richness of the microorganisms in the soil were very similar to those in roots but higher than those in other tissues of P. ludlowii. Predictive metagenome analysis revealed that endophytic bacteria play critical functional roles in P. ludlowii. This conclusion could facilitate the study of the ecological functions of endophytic bacteria and their interactions with P. ludlowii to analyze the reasons why this important medicinal plant is becoming endangered.

Comparative Study on Pharmacokinetics of Four Active Compounds in Rat Plasma after Oral Administration of Raw and Wine Processed Chuanxiong Rhizoma.

In Chinese medicine, the effect of promoting blood circulation and removing stasis could be enhanced after Chuanxiong Rhizoma is processed by wine. However, the relevant mechanism remains unclear. In this manuscript, a rapid and sensitive quantification method employing ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established and validated to simultaneously determine butylidenephthalide, ligustilide, senkyunolide A and ferulic acid in rat plasma after oral administration of raw Chuanxiong Rhizoma (RCR) and wine-processed Chuanxiong Rhizoma (WCR) respectively. All analytes were extracted from plasma by proteins precipitation with methanol. Chromatographic separation was carried out on a Hypersil GOLD C18 column by using a gradient mobile phase system of acetonitrile and water with 0.01% formic acid, the flow rate was 0.3 mL/min. For exact mass detecting, quick switching mode was used, positive and negative ions could be detected in one injection. The pharmacokinetic profiles of four components in the two groups were evaluated and compared. The results showed that, compared to the RCR group, the Vd and AUC0→t values of four active compounds were increased and decreased respectively in WCR group, which revealed the effect of wine processing to Chuanxiong Rhizoma: the stronger the effect, the wider the distribution.

Development of an UHPLC-MS/MS method for comparative pharmacokinetics of nine anthraquinones in rats and application to dosage conversion between different Semen Cassiae forms.

Semen Cassiae, called Juemingzi in Chinese, is widely used in clinic for alleviating constipation, improving eyesight and preventing hyperlipidemia. It can be used as medicine or food including many application forms, such as traditional pieces and ultrafine granular powder (UGP). In this paper, comparative pharmacokinetics of Semen Cassiae in different forms of traditional pieces and UGP were achieved to research the clinical dosage of UGP. Also, the scientific connotation of brewing way for traditional pieces of Semen Cassiae application in clinic was revealed. To achieve this purpose, a rapid, sensitive and reliable UHPLC-MS/MS method was developed for simultaneous determination of rhein, emodin, aloe-emodin, chrysophanol, physcion, aurantio-obtusin, chryso-obtusin, obtusifolin and obtusin in rat plasma. Multiple reaction monitoring mode via an electrospray ionization was applied for the quantitation of the analytes. The separation was carried out on an Agilent Extend-C18 column (100 mm × 2.1 mm, 1.8 µm) with an 8.0 min gradient elution using ultra-purify water and acetonitrile as mobile phase. The samples were prepared by liquid-liquid extraction with ethyl acetate. The development and validation of bioanalytical method were performed according to the latest "Bioanalytical Method Validation: Guidance for Industry" issued by FDA in 2018. Finally, the clinical dosage of UGP was concluded to be 1/4 of Semen Cassiae traditional pieces in oral administration way by comparing the pharmacokinetic parameters of UGP to that of traditional pieces in the aspect of mathematical statics using plus of AUC values.

Investigation on Spectrum-Effect Correlation between Constituents Absorbed into Blood and Bioactivities of Baizhu Shaoyao San before and after Processing on Ulcerative Colitis Rats by UHPLC/Q-TOF-MS/MS Coupled with Gray Correlation Analysis.

Baizhu Shaoyao San (BSS) is a crucial traditional Chinese medicinal formula widely applied for the treatment of painful diarrhea, diarrhea-predominant irritable bowel syndrome, ulcerative colitis, and some other gastrointestinal diseases. Corresponding to the clinical medication, the three medicinal herbs (Atractylodis Macrocephalae Rhizoma, Paeoniae Radix Alba, and Citri Reticulatae Pericarpium) included in BSS should be processed using some specific methods of stir-frying. To find the underlying correlations between serum chemical profiles and curative effects of crude and processed BSS on ulcerative colitis rats, and further explore for the effective material basis of processing, an UHPLC/Q-TOF-MS/MS technique coupled with gray correlation analysis (GCA) was developed. A total of 134 compounds were identified in rat sera after oral administration of BSS, among which 24 compounds were prototypes and 110 compounds were metabolites. Meanwhile, an ulcerative colitis model was established in rats by enema with 2,4,6-trinitrobenzene sulfonic acid, and the pharmacodynamic indicators for drug efficacies were evaluated as well. According to the results, processed BSS showed better efficacy than crude BSS. The top 10 potential effective components with high degree of correlation were identified based on GCA results, which were thought to be the crucial compounds that contributed to the enhancement of therapeutic effects in BSS after processing.

Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil-based adjuvant chemotherapy benefit.

The current study suggests that the identification of predictive signatures of fluorouracil (5-FU) response for stage II and III colorectal cancer (CRC) could be confounded by chemotherapy-irrelevant low relapse risk. Using the samples of patients with stage II and III CRC who were treated with curative surgery only, we identified a signature with which to predict chemotherapy-irrelevant relapse risk for patients after curative surgery. By applying this signature to the samples of patients with stage II and III CRC who were treated with 5-FU-based adjuvant chemotherapy (ACT) after surgery, we predicted the relapse risk if treated with surgery only. From high-risk samples, we further identified another signature with which to predict therapeutic benefit from 5-FU-based ACT. On the basis of the relative expression orderings of gene pairs, a postsurgery relapse risk signature that consisted of 44 gene pairs was developed and verified in 3 independent data sets. A 5-FU therapeutic benefit signature that consisted of 4 gene pairs was then developed to predict the response of 5-FU-based ACT for those patients with high relapse risk after curative surgery. The signature was verified in 4 independent datasets. For patients with stage II and III CRC, the coupled signatures can first identify patients with high relapse risk after curative surgery, then predict therapeutic benefit from 5-FU-based ACT.-Song, K., Guo, Y., Wang, X., Cai, H., Zheng, W., Li, N., Song, X., Ao, L., Guo, Z., Zhao, W. Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil-based adjuvant chemotherapy benefit.

Ultra-high-performance liquid chromatography with tandem mass spectrometry method for determination of four compounds in rat plasma after oral administration of Xanthii fructus and stir-fried Xanthii fructus extracts.

Xanthii fructus (XF), the fruit of Xanthium sibiricum Patr., is a traditional Chinese materia medica commonly used to treat allergic rhinitis and other rhinitis diseases. To uncover the mechanism of the stir-frying process and its effect on the pharmacokinetic behavior of active compounds in model rats, four active compounds-chlorogenic acid, 4-caffeoylquinic acid, 1,5-O-dicaffeoylquinic acid and apigenin-were selected based on previous spectrum-effect experiments. High performance liquid chromatography tandem triple quadrupole mass spectrometry (UPLC-QqQ-MS) technology, an accurate and feasible method, was applied to measure the concentration of these four compounds in rat plasma. This validated method can accurately measure the concentration of each compound at each sampling point of rat plasma. This validated method shows good linearity, extraction recoveries, matrix effects, intra- and inter-day precision and stabilities. Compared with the XF group, the maximum plasma concentration (Cmax ) value of 1,5-O-dicaffeoylquinic acid decreased remarkably (p < 0.05) after oral administration of stir-fried Xanthii fructus (SXF) extract, while the other compounds showed no significant difference. The mean residence time value of chlorogenic acid (p < 0.05) and 1,5-O-dicaffeoylquinic acid (p<0.01) after oral administration of SXF extraction demonstrated significant differences compared with the XF group, while the other two compounds showed no statistical difference, indicating that the stir-frying process prolonged the effect time and delayed the removal time of chlorogenic acid and 1,5-O-dicaffeoylquinic acid. The values of the area under the plasma concentration-time curve from zero to the last quantifiable time-point, the area under the plasma concentration-time curve from zero to infinity, the time to maximum concentration and the elimination half-life of four compounds in the SXF group showed no statistically significant difference from the XF group. From this data, we speculated that the stir-frying process can not only keep the absorption of 4-caffeoylquinic acid and apigenin, but also increase the effect time of chlorogenic acid and 1,5-O-dicaffeoylquinic acid, which could be the mechanism underlying the stir-frying process enhancing the effects of XF.

Identification and Analysis of Compound Profiles of Sinisan Based on 'Individual Herb, Herb-Pair, Herbal Formula' before and after Processing Using UHPLC-Q-TOF/MS Coupled with Multiple Statistical Strategy.

Sinisan has been widely used to treat depression. However, its pharmacologically-effective constituents are largely unknown, and the pharmacological effects and clinical efficacies of Sinisan-containing processed medicinal herbs may change. To address these important issues, we developed an ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method coupled with multiple statistical strategies to analyze the compound profiles of Sinisan, including individual herb, herb-pair, and complicated Chinese medicinal formula. As a result, 122 different constituents from individual herb, herb-pair, and complicated Chinese medicinal formula were identified totally. Through the comparison of three progressive levels, it suggests that processing herbal medicine and/or altering medicinal formula compatibility could change herbal chemical constituents, resulting in different pharmacological effects. This is also the first report that saikosaponin h/i and saikosaponin g have been identified in Sinisan.

[Problems and solutions in modern research of traditional Chinese herbal pieces processing technology].

Chinese medicine processing is the main feature that distinguishes traditional Chinese medicine from natural medicine and plant medicine, and is the main feature in clinical medication of traditional Chinese medicine. The research of Chinese medicine processing technology is an important link to realize standardization and standardization of Chinese herbal pieces, with urgent need to attract high attention. At present, there are still many problems in the research of processing technology of Chinese herbal pieces, mainly including inconsistent processing technology, large differences in process technology parameters, and unstable production technology of Chinese herbal pieces, resulting in uncontrollable quality of Chinese herbal pieces and affecting the clinical efficacy of Chinese medicine. This paper focused on the establishment of a unified standard processing technology, and put forward the countermeasures for the processing technology of Chinese medicine based on a comprehensive analysis of the current situations of the processing technology of Chinese herbal pieces, with significance for guiding the establishment of a standardized processing technology of Chinese medicine.

Distribution patterns for metabolites in medicinal parts of wild and cultivated licorice.

Licorice is a famous Chinese medicinal material widely applied worldwide in food and drugs. It possesses a substantial share in the international and domestic markets. While the demand is continuously increasing, wild-type of licorice is gradually disappearing. Its cultivated-type is significantly different compared to its wild-type, especially the bioactive compounds in dried roots and rhizomes (the medicinal parts of wild and cultivated licorice) are responsible for their quality difference. In this study, a total of thirty-two constituents, including seventeen secondary compounds and fifteen primary metabolites, were simultaneously analyzed by UFLC coupled with triple quadrupole-linear ion trap mass spectrometry (UFLC-QTRAP-MS/MS) in different medicinal parts of licorice. Our findings indicated that the content of major bioactive compounds in wild licorice were significantly higher than those in its cultivated-type. The metabolites in rhizomes showed totally different outcomes between wild and cultivated licorice. Remarkably high level of some important amino acids related to abiotic stress (drought and salt) were found in wild licorice. Notably, the high contents of phenylalanine and compounds in upstream of flavonoid synthesis in cultivated licorice suggested that the synthesis may differ at the initial stage. The distribution pattern of metabolites in different medicinal parts of wild and cultivated licorice will not only provide a novel clue in agricultural breeding but also facilitate the further study on their quality formation.

Study on spectrum-effect correlation for screening the effective components in Fangji Huangqi Tang basing on ultra-high performance liquid chromatography-mass spectrometry.

BACKGROUD: Fangji Huangqi Tang (FHT) is a traditional Chinese medicine formula. Our previous work found that FHT could improve glomerular filtration function. The research on the effective materials basis of FHT was rarely reported. PURPOSE: The effect indicators of glomerular filtration function were determined. The components in serum of FHT was detected and identified. The relationships between chemical spectra of serum and effect indicators were elucidated. STUDY DESIGN: The paper was to study the underlying correlations between the chemical spectra and the protective effect of FHT on glomerulus to reveal the potential effective compounds in FHT. METHODS: For the serum pharmacochemistry study, the biological samples were collected according to a time schedule designed carefully in advance. The fingerprint chromatograms of rat serum after oral administration of FHT were established by UHPLC-ESI-Q-TOF-MS technique. Meanwhile, in the pharmacodynamics research, the protective effects of FHT on glomerulonephritis were evaluated by detecting the contents of cystatin C (Cys C), blood urea nitrogen (BUN) and serum creatinine (Scr). Then, the spectrum-effect relationships between UHPLC fingerprints and anti-adriamycin nephrosis activities were evaluated using canonical correlation analysis (CCA) statistical method. RESULTS: As a result, 105 peaks were identified from rat serum samples, which turned out to be 26 original compounds of FHT as well as 79 metabolites. According to the CCA results, eleven components were finally found to be the main anti-adriamycin nephrosis components. CONCLUSIONS: The model successfully discovered the spectrum-effect relationships of FHT, which showed a representative way to discover the primary active ingredients from the complex herbal medicine system.

Discrimination of volatiles in herbal formula Baizhu Shaoyao San before and after processing using needle trap device with multivariate data analysis.

To characterize the chemical differences of volatile components between crude and processed Baizhu Shaoyao San (BSS), a classical Chinese herbal formula that is widely applied in the treatment of gastrointestinal diseases, we developed a gas chromatography-mass spectrometry-based needle trap device combined with multivariate data analysis to globally profile volatile components and rapidly identify differentiating chemical markers. Using a triple-bed needle packed with Carbopack X, DVB and Carboxen 1000 sorbents, we identified 121 and 123 compounds, respectively, in crude and processed BSS. According to the results of principal component analysis and orthogonal partial least-squares discriminant analysis, crude and processed BSS were successfully distinguished into two groups with good fitting and predicting parameters. Furthermore, 21 compounds were identified and adopted as potential markers that could be employed to quickly differentiate these two types of samples using S-PLOT and variable importance in projection analyses. The established method can be applied to explain the chemical transformation of Chinese medicine processing in BSS and further control the quality and understand the processing mechanism of Chinese herbal formulae. Besides, the triple-bed needle selected and optimized in this study can provide a valuable reference for other plant researches with similar components. Furthermore, the systematic research on compound identification and marker discrimination of the complex components in crude and processed BSS could work as an example for other similar studies, such as composition changes in one plant during different growth periods, botanical characters of different medicinal parts in same kind of medicinal herbs and quality identification of one species of medicinal herb from different regions.

A metabolomics research based on UHPLC-ESI-Q-TOF-MS coupled with metabolic pathway analysis: Treatment effects of stir-frying Xanthii Fructus on allergic rhinitis in mice model.

Xanthii Fructus (XF), a well-known herb in traditional Chinese medicine, has been frequently used for the treatment of allergic rhinitis in the clinic. Its therapeutic metabolic mechanism, however, remains undetermined. In this work, a metabolomics research coupled with metabolic pathway analysis has been employed to screen out the potential mechanism in its effects on allergic rhinitis. Specifically, mouse serum samples containing XF were analyzed based on ultra-high performance liquid chromatography equipped with electrospray ionization quadruple time-of-flight mass spectrometry detection (UHPLC-ESI-Q-TOF-MS) in both positive and negative polarity. In addition, the raw data gained from UHPLC-ESI-Q-TOF-MS were processed by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) in order to discover remarkable metabolites. Twenty-seven potential biomarkers in mouse serum were filtered from free databases like HMDB. Interestingly, this study filtered the potential metabolic pathways including glycerophospholipid metabolism and branch-chain amino acid metabolism. We hope that this paper will provide a feasible strategy for revealing the therapeutic mechanism of XF in allergic rhinitis mice model.

[Research progress on antidepressant effects of Sini San based on three progressive levels of "single herb, herb-pair, and complicated Chinese herbal formula"].

Depression is a kind of mental illness accompanied by complex etiology and pathogenesis in clinic. With the quickening pace of circadian rhythm and increase of life pressure in modern society, the incidence of depression is increasing year by year. Nowadays, some typical antidepressant Western medicines, such as selective serotonin re-uptake inhibitors (SSRI) and tricyclic antidepressants (TCA), have been used as the main therapeutic drugs in clinic. Unfortunately, administration of these drugs will result in severe adverse reactions, slow treatments, and low cure rates, thus obviously they can not be used for a long term. Sini San, which originated from Treatise on Febrile Diseases written by Zhang zhongjing, is a prescription widely applied in clinic for curing mental illness and also a basic Chinese herbal formula for modern treatment of depression. This article would review the research progress on antidepressant effects of Sini San based on single herbs of Bupleuri Radix and Paeoniae Radix Alba, herb-pair of Bupleuri Radix-Paeoniae Radix Alba, and formula of Sini San, providing directions and ideas for future research on complicated Chinese herbal formulae.