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Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.
Subject(s)
Rats , Animals , Chromatography, Liquid , Gardenia , Tandem Mass Spectrometry , Gastrointestinal Microbiome , alpha-Linolenic Acid , Metabolomics/methods , Arthritis, Rheumatoid/drug therapy , Inflammation , GlycerophospholipidsABSTRACT
This study used bioinformatics analysis to screen out key genes involved in the transformation of idiopathic membranous nephropathy to end-stage renal disease and to predict targeted Chinese herbs and medicines and active ingredients with preventive and curative effects. The GSE108113 microarray of idiopathic membranous nephropathy and GSE37171 microarray of were downloaded from the comprehensive gene expression database, and 8 homozygous differentially expressed genes for the transformation of idiopathic membranous nephropathy into end-stage renal disease of were screened out by R software. GraphPad Prism was used to verify the expression of homozygous differentially expressed genes in GSE115857 microarray of idiopathic membranous nephropathy and GSE66494 microarray of chronic kidney disease, and 7 key genes(FOS, OGT, CLK1, TIA1, TTC14, CHORDC1, and ANKRD36B) were finally obtained. The Gene Ontology(GO) analysis was performed. There were 209 functions of encoded proteins, mainly involved in regulation of RNA splicing, cytoplasmic stress granule, poly(A) binding, etc. Thirteen traditional Chinese medicines with the effect of preventing the transformation of idiopathic membranous nephropathy to end-stage renal disease were screened out from Coremine Medical database, including Ginseng Radix et Rhizoma, Lycopi Herba, and Gardeniae Fructus, which were included in the Chinese Pharmacopoeia(2020 edition). The active ingredient quercetin mined from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) had ability to dock with the key gene FOS-encoded protein molecule, which provided targets and research ideas for the development of new traditional Chinese medicines.
Subject(s)
Humans , Medicine, Chinese Traditional , Glomerulonephritis, Membranous , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Computational BiologyABSTRACT
Depression is a mental disorder characterized by persistent low mood and belongs to the category of "stagnation syndrome" in traditional Chinese medicine （TCM）， with the characteristics of high prevalence， high disability rate， high suicide rate， and high recurrence rate. The pathogenesis of depression is extremely complex and involves factors such as genetics， psychology， and social environment. Currently， clinical antidepressant drugs such as tricyclic and tetracyclic antidepressants， and selective serotonin reuptake inhibitors， have slow onset of action and significant adverse effects with long-term application. Furthermore， clinical statistics show that about one-third of patients do not respond to these types of medications. Enhancing the effectiveness of depression treatment has become a major challenge in the medical field. TCM， based on the holistic view and treatment based on syndrome differentiation， has unique advantages in the prevention and treatment of depression， including stable therapeutic effects， low recurrence rate， minimal side effects， and good patient compliance. As one of the heat-clearing drugs， Gardeniae Fructus has the effects of clearing heat， purging fire， cooling blood， and relieving restlessness， which makes it effective in treating patients with "stagnation syndrome". Literature studies have found that active components of Gardeniae Fructus， such as geniposide， genipin， and crocin， as well as drug pairs such as Gardeniae Fructus-Chuanxiong Rhizoma， Gardeniae Fructus-Acanthopanacis Senticosi Radix et Rhizoma Seu Caulis， and Gardeniae Fructus-Lycii Fructus， and prescriptions such as Zhizichi Tang， Yuejuwan， Zhizi Houpotang， Danzhi Xiaoyaosan， and Jieyu Anshen Granules， have shown significant antidepressant effects. The mechanism of action may be related to regulating the hypothalamic-pituitary-adrenal （HPA） axis， modulating neurotransmitters such as serotonin （5-HT） and dopamine （DA）， increasing brain-derived neurotrophic factor （BDNF） in the hippocampus， enhancing neurogenesis in the hippocampus， and regulating the nuclear factor-kappa B （NF-κB） signaling pathway to inhibit neuroinflammation. This article summarized the research progress on the active components of Gardeniae Fructus， drug pairs， and Chinse medicinal prescriptions containing Gardeniae Fructus， providing references for further promoting the clinical application of Gardeniae Fructus and its prescriptions in the treatment of depression.
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ObjectiveTo optimize the extraction and purification process of Gardeniae Fructus for industrial production， and to obtain the total iridoid and total crocin extracts. MethodOrthogonal test was used to optimize the water extraction process by taking contents of geniposide， genipin gentiobioside， gardenoside， crocin-1 and crocin-2 as indicators and the decocting time， decocting times and water amount as factors. The purification process was optimized by single factor test， and four different types of macroporous adsorption resins were screened. The process conditions such as resin type， maximum loading amount， water washing amount， ethanol concentration， ethanol dosage， and flow rate of sample loading were mainly investigated. In addition， the drying methods （vacuum drying and spray drying） of the extract were investigated， and a pilot scale-up verification test was carried out. ResultThe optimal water extraction process of Gardeniae Fructus was to add 15， 10 times the amount of water for decocting twice， 1 h each time. The optimal purification process was as follows：the water extract through SP825L macroporous resin column， the amount of crude drug-the amount of resin （1∶1.5）， the sample loading flow rate of 3 BV h-1， adding 2 BV of water to remove impurities， adding 4 BV of 30% ethanol to obtain the iridoid part， then adding 3 BV of 70% ethanol to obtain the crocin part， collecting the ethanol lotion， and drying at 70 ℃. Under these conditions， the extraction amount of total iridoids was 590.75 mg·g-1 with the transfer rate of 70.48%， and the yield of dry extract was 8.89%. The extraction amount of total crocins was 83.37 mg·g-1 with the transfer rate of 22.20%， and the dry extract yield was 2.60%. ConclusionThe optimized extraction and purification process is stable and feasible with high extraction rate of active components， which is suitable for the industrial extraction and purification of active parts of Gardeniae Fructus.
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ObjectiveTo study the chemical structure of gardenia blue pigment and its inhibitory activity against monoamine oxidase B （MAO-B）， in order to seek a potential feasible way for rational utilization and value enhancement of iridoids in Gardeniae Fructus. MethodIridoid glycosides in Gardeniae Fructus were hydrolyzed by cellulase to obtain their aglycones and reacted with amino acids. Then， the products were purified by column chromatography packed with D101 macroporous resin and preparative liquid chromatography to obtain gardenia blue pigments， and the gardenia blue pigments were identified by nuclear magnetic resonance （NMR） and mass spectrometry （MS）. Benzylamine was used as the reaction substrate of MAO-B and in vitro incubated with gardenia blue pigment monomers， high performance liquid chromatography （HPLC） was employed to determine the production of benzaldehyde for evaluating the inhibitory effect of gardenia blue pigments on MAO-B， the mobile phase was methanol （A） -50 mmol·L-1 potassium phosphate buffer （B， pH 3.2） （2∶3）， and the detection wavelength was 245 nm. ResultEight compounds of gardenia blue pigment A-H were synthesized and identified. In MAO-B inhibition test， compared with geniposide， the inhibitory activity of gardenia blue pigment D and E was significantly enhanced （P<0.05）. Compared with the 6β-hydroxygeniposide， the inhibitory activity of gardenia blue pigment G and H was significantly enhanced （P<0.05， P<0.01）. All the four gardenia blue pigments showed better MAO-B inhibitory activity than the prototype compounds. ConclusionGardenia blue pigment is a simple compound formed by one molecule of amino acid and one molecule of iridoid. Some gardenia blue pigments have better MAO-B inhibitory activity than the prototype compounds. The activity of gardenia blue pigment produced by different substrates is different， and the high-value gardenia blue pigment can be prepared based on experimental optimization， which can expand the application range of gardenia blue pigment and enrich the comprehensive utilization of iridoids from Gardeniae Fructus.
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The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Fruit , GardeniaABSTRACT
Objective:Combined with high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （HPLC-Q-TOF-MS/MS） and network pharmacology， to predict the target and potential mechanism of Gardeniae Fructus in the treatment of cerebral ischemia. Method:HPLC-Q-TOF-MS/MS was used to identify the chemical constituents of Gardeniae Fructus according to the retention time， relative molecular weight， secondary mass spectrometry fragmentation and other information of chromatographic peaks， and combined with literature data. The targets of main active ingredients in Gardeniae Fructus were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction database. The potential targets of Gardeniae Fructus against cerebral ischemia were obtained through Online Mendelian Inheritance in Man （OMIM）， GeneCards and Kyoto Encyclopedia of Genes and Genomes （KEGG）. Gene ontology （GO） function enrichment and KEGG pathway analysis of potential targets were analyzed with the DAVID 6.8. Cytoscape 3.6.0 software was used to construct the network of active components-targets-pathways. At last， Discovery Studio 2016 software was applied in the molecular docking verification between the key active ingredients and potential protein targets. Result:A total of 40 chemical constituents in Gardeniae Fructus were identified， including iridoids， diterpenoid pigments， organic acids， monoterpenoids and other components. According to the main active ingredients， 208 potential targets were predicted， 560 disease targets related to cerebral ischemia were retrieved， 59 key targets were selected by mapping component targets with disease targets. These targets could act on key target proteins such as tumor necrosis factor （TNF）， Caspase-3 （CASP3） and CASP8， and participate in the regulation of TNF， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， hypoxia inducible factor 1 （HIF-1） and other signal pathways. Molecular docking results showed that geniposide could interact with targets of prostaglandin G/H synthase 2 （PTGS2）， TNF<italic> </italic>and nuclear transcription factor-<italic>κ</italic>B p65 （RELA）， crocin Ⅰ could interact with interleukin-2 （IL-2）. Conclusion:Geniposide， crocin Ⅰ and other ingredients in Gardeniae Fructus can play a role of anti-inflammatory and inhibiting apoptosis to prevent or treat cerebral ischemic diseases by up-regulating protein expression level of RELA and IL-2， down-regulating protein expression level of TNF， CASP8， CASP3 and matrix metalloproteinase 2 （MMP2）， and regulating TNF， PI3K/Akt and HIF-1 signaling pathways.
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To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.
Subject(s)
Animals , Rats , Drugs, Chinese Herbal/toxicity , Fruit , Gardenia , Liver , Proteomics , Signal TransductionABSTRACT
Objective: To compare the differences of Gardeniae Fructus and its stir-baked preparation and screen out the differential markers, and provide reference for the establishment of quality standard. Methods: The whole and partial fingerprints of Gardeniae Fructus and its stir-baked prepared slices were established by HPLC-UV analysis. And the fingerprints were statistically analyzed using hierarchical clustering analysis (HCA), principle component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA), then the characteristic markers were screened out. And then content of 6-α-hydroxygeniposide, gentioside, geniposide, crocin I, and crocin II was determined. Results: A total of 15 peaks were acquired for Gardeniae Fructus and stir-baked Gardeniae Fructus respectively, 12 peaks of which were the common peaks. The similarity of whole and partial reference fingerprints of Gardeniae Fructus and its stir-baked prepared slices was 0.991 and 0.880, respectively, and partial fingerprint can successfully distinguished Gardeniae Fructus from its stir-baked prepared slices. HCA and OPLS-DA results showed that significant differences were observed between Gardeniae Fructus and stir-baked Gardeniae Fructus with peak 3, peak 5, peak 9 (geniposide), and peak 11 (crocin I), which being identified as the main differential markers. Contents of geniposide, crocin I and crocin II in Gardeniae Fructus were higher than those in stir-baked Gardeniae Fructus, while 6-α-hydroxygeniposide was lower. Conclusion: The composition was significantly different before and after stir-baked. The established partial fingerprints combined with multi-component determination method can effectively distinguish them. And the differential markers obtained by multivariate statistical analysis can provide reference for the selection of quality markers.
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In this study, the contents of Cu, As, Cd, Pb and Hg in 10 batches of Gardeniae Fructus and 10 batches of fried Gardeniae Fructus from Fuzhou in Jiangxi were determined by inductively coupled plasma mass spectrometry(ICP-MS), and the target hazard coefficient(THQ) for different drug users(adults and children) was calculated by using the international health risk assessment model. According to the ISO and green industry standard, the content of Hg in 4 batches of Gardeniae Fructus exceeded the standard with an over-standard rate of 40%. The THQ and total THQ of Hg in 2 batches of Gardeniae Fructus were higher than the international standard limit of Gardeniae Fructus. For 10 batches of fried Gardeniae Fructus, the content of every heavy metal and total amount of five heavy metals did not exceed the standard. However, the THQ and total THQ of Hg in 1 batch of fried Gardeniae Fructus were higher than the international standard limit of Gardeniae Fructus. As compared with Gardeniae Fructus, the contents of Cu, Pb and Hg in fried Gardeniae Fructus decreased by 34.0%, 77.6% and 23.1%; the THQ of Cu, Pb and Hg for adults decreased by 33.3%, 75.0% and 96.9%; and the THQ of Cu, Pb and Hg for children decreased by 37.5%, 75.0%, 90.7%. It showed that the contents of heavy metals in individual batches of Gardeniae Fructus in this experiment had a certain risk to human health, but the contents of these heavy metals in fried Gardeniae Fructus had no obvious effect on human health. This study provided experimental basis and research ideas for safety evaluation of Gardeniae Fructus and fried Gardeniae Fructus.
Subject(s)
Adult , Child , Humans , Drugs, Chinese Herbal , Gardenia , Mercury , Metals, Heavy , Risk AssessmentABSTRACT
Gardeniae Fructus has the traditional effects of promoting intelligence and inducing resuscitation, but its mechanism is unclear. In this study, the relationship between Gardeniae Fructus's traditional effect of promoting intelligence and inducing resuscitation and anti-Alzheimer's disease effect was taken as the starting point to investigate the anti-Alzheimer's disease mechanism of the major absorbed components in Gardeniae Fructus by the network pharmacology method. The network pharmacology research model of "absorbed composition-target-pathway-disease" was adopted. In this study, the active components screening and target prediction technology were used to determine the active components and targets of Gardeniae Fructus in treatment of Alzheimer's disease. The enrichment pathway and biological process of Gardeniae Fructus were studied by using the bioinformatics annotation database(DAVID), and the results of molecular docking validation network analysis were used to elaborate the mechanism of Gardeniae Fructus in treatment of Alzheimer's disease. It was found that 35 absorbed components of Gardeniae Fructus not only regulated 48 targets such as cholines-terase(BCHE) and carbonic anhydrase 2(CA2), but also affected 11 biological processes(e.g. transcription factor activity, nuclear receptor activity, steroid hormone receptor activity, amide binding and peptide binding) and 7 metabolic pathways(MAPK signaling pathway, Alzheimer disease and estrogen signaling pathway, etc.). Molecular docking results showed that more than 60% of the active components could be well docked with key targets, and the relevant literature also showed that the active components could inhibit the MAPK1 expression of key targets, indicating a high reliability of results. These results indicated that Gardeniae Fructus may play its anti-Alzheimer's disease action via a "multi-ingredients-multi-targets and multi-pathways" mode, providing a scientific basis for further drug research and development.
Subject(s)
Humans , Alzheimer Disease , Drugs, Chinese Herbal , Gardenia , Molecular Docking Simulation , Reproducibility of ResultsABSTRACT
This research is to establish an HPLC method for determination of geniposidic acid, genipin-1-β-D-gentiobioside, geniposide, p-trans-coumaroylgenipin gentiobioside, chlorogenic acid, crocin-Ⅰ, crocin-Ⅱ and crocin-Ⅲ in Gardeniae Fructus at different harvest time. The detection wavelength was 238, 320 and 440 nm. Principal component analysis(PCA), correlation analysis, regression analysis and partial least squares(PLS) analysis were used to explore the relationship of color and content of eight components in Gardeniae Fructus. The result showed that the trend of the eight components in Gardeniae Fructus at harvest time in different three years was varied similarly. According to the variation of eight components at different harvest time, the mature and immaturate Gardeniae Fructus were discriminated. The content of crocin-Ⅰwas correlated positively with a~* of color significance. The redder color of Gardeniae Fructus showed the higher value of a~* and content of crocin-Ⅰ, indicating the better quality of Gardeniae Fructus. This method provided reference for justifying the color and quality of Gardeniae Fructus and scientific evidence for "assessing quality by distinguishing color".
Subject(s)
Chlorogenic Acid , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Fruit , GardeniaABSTRACT
The chromaticity space parameters of the samples during the processing of Gardeniae Fructus Praeparatus(Jiaozhizi in Chinese herbal name, JZZ) were measured by the visual analyzer to analyze the color variation rule during the processing of JZZ, and the content changes of total reducing sugar, total amino acid and 5-hydroxymethylfurfural(5-HMF) related to Maillard reaction were measured. Pearson correlation analysis and linear regression analysis of the data were carried out by SPSS 24.0 software. The experimental results showed that the objective coloration of the samples in the processing of JZZ was basically consistent with the traditional subjective color judgment; the contents of total reducing sugar and total amino acids showed a decreasing trend during the processing of JZZ, and the content of 5-HMF showed an increasing trend, which was in line with Maillard reaction law. Pearson correlation analysis results showed that there was a significant correlation between the chromaticity space parameters L~*(lightness value), a~*(red green value), b~*(yellow blue value), E~*ab(total color value) and the contents of total reducing sugar, total amino acid and 5-HMF(P<0.01), among which the values of L~*, a~*, b~*, E~*ab were positively correlated with the contents of total reducing sugar and total amino acid, and negatively correlated with the contents of 5-HMF. The results of linear regression analysis also showed that these two were highly correlated. In this study, by establishing the correspondence relationship between the color change of JZZ processing and Maillard reactants, wecan not only provide a basis for the objective digital expression of subjective color of JZZ, but also provide a reference for explaining the processing mechanism of JZZ from a new perspective.
Subject(s)
Amino Acids , Color , Drugs, Chinese Herbal , Fruit , Gardenia , Maillard ReactionABSTRACT
Gardeniae Fructus (GF) and Semen Sojae Praeparatum (SSP) are both medicine food homologies and widely used in Chinese clinical prescriptions together. The research investigated the pharmacokinetics of four iridoids in normal rats and isolfavones-fed rats, which were administered with isolfavones from SSP for 7, 14, 21 and 28 consecutive days. A validated LC-MS/MS method was developed for determining shanzhiside, genipin-1-gentiobioside, geniposide and their metabolite genipin in rat plasma. Plasma samples were pretreated by solid-phase extraction using paeoniflorin as the internal standard. The chromatographic separation was performed on a Waters Atlantis T3 (4.6 mm × 150 mm, 3μm) column using a gradient mobile phase consisting of acetonitril and water (containing 0.06％acetic acid). The mass detection was under the multiple reaction monitoring (MRM) mode via polarity switching between negative and positive ionization modes. The calibration curves exhibited good linearity (r>0.997) for all components. The lower limit of quantitation was in the range of 1-10 ng/mL. The intra-day and inter-day precisions (RSD) at three different levels were both less than 12.2％ and the accuracies (RE) ranged from -10.1％ to 16.4％. The extraction recovery of them ranged from 53.8％ to 99.7％. Pharmacokinetic results indicated the bioavailability of three iridoid glycosides and the metabolite, genipin in normal rats was higher than that in rats exposed to isoflavones. With the longer time of administration of iso-flavones, plasma concentrations of iridoids decreased, while genipin sulfate, the phase II metabolite of genposide and genipin-1-gentiobioside, appeared the rising exposure. The pharmacokinetic profiles of main iridoids from GF were altered by isoflavones.
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Objective:To investigate the effective substance of the choleretic effect of Gardeniae Fructus，and analyze the relationships between its choleretic effect and the HPLC fingerprint chromatogram. Method:HPLC method was applied to establish the fingerprint chromatography of 8 batches of Gardeniae Fructus at different harvest periods. The flow，the content of bile acid，bilirubin and cholesterol in bile were tested，and then the principal component analysis was used to comprehensively evaluate the total choleretic effects of Gardeniae Fructus. After the relationships between the relative peak area of the common peaks and the choleretic effects were explored using grey relationship analysis method，the spectrum-effect relationship of Gardeniae Fructus was established. Result:The order of the contribution of the chemical components to the choleretic effect at the common peaks was as follow（r>0.8）：P9>P14>P26>P4>P30>P6>P1>P10>P5>P24. Among all peaks，the full wavelength scanning results implied that the peaks 9，14 and 4 might be iridoids, and the peaks 26，30 and 24 might be crocins. By comparing with the standard substances，the peak 9 was finally identified as geniposide. Conclusion:The choleretic effect of Gardeniae Fructus may be the results of multiple components and pathways，and the main components in Gardeniae Fructus with the choleretic effect was from geniposide. In conclusion，these results provide a reference for investigating the material basis of choleretic effect of Gardeniae Fructus.
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Gardenia has been widely used in clinical practice and with a long history. In order to make better use of gardenia resources，this study summarized historical literatures and modern researches，made textual research on the name，variety，origin，processing and efficacy of Gardenia jasminoides，and found that the name of G. jasminoides mainly reflects the characteristics of G. jasminoides based on form and color to a certain extent. In some cases, the name "Huangzhi" was mixed with water G. jasminoides. The earliest origin of G.jasminoides was Nanyang as recorded in ancient literatures, but with a low yield. Due to the influence of population migration and productivity development，the main origin of G. jasminoides moved to the south，and southern producers were preferred. G. jasminoides was recorded as G. jasminoides, and Gardeniae Fructus could not be used as medicine in literatures of Chinese materia medica，but there were records of "Fat G.jasminoides" and "Great G. jasminoides" as medicines in ancient books of treatment for febrile diseases. The reason for the difference with the literature records of this herb lay in different eras of "Leigong Bombardment Theory" and "Treatise on Febrile Diseases". There were gaps in the yield and harvesting capacity of G.jasminoides，and the herbaceous book was highly standardized， the highest-quality herbs were selected to be used as medicine，and the formularies focused on practicality. According to modern experimental studies，chemical composition and content of Gardeniae Fructus and Gardeniae Fructus were similar with the same choleretic effect. In addition，the processing history and efficacy application of G. jasminoides were also summarized，in order to provide reference for the further study and utilization of G. resources.
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Depression is a kind of emotional and mental disorder， which is related to many pathogenic factors， such as abnormal metabolism of monoamine neurotransmitters， immune inflammatory reaction， neuroendocrine disorder and so on. it has the characteristics of high disability rate and high recurrence rate， which is seriously harmful to human health. It brings huge economic burden to patients and their families. At present， the commonly used antidepressants in clinic are monoamine oxidase inhibitors， tricyclic antidepressants and selective 5-hydroxytryptamine reuptake inhibitors. Long-term use causes adverse reactions such as cardiovascular， urinary and digestive dysfunction. The multi-target， multi-pathway and multi-mechanism of traditional Chinese medicine has played a great role in the treatment and rehabilitation of depression. At the same time， traditional Chinese medicine has gradually become a hot spot in the research and development of antidepressants because of its small side effects and good drug compliance. Especially the ZHANG Zhong-jing's classical formulae with precise medication and rigorous prescription has unique advantages in the treatment of depression. For thousands of years， it has been used clinically by countless doctors in the treatment of various types of depression， with definite curative effects and few side effects. In recent years， clinical research， experimental research， and pharmacological research around ZHANG Zhong-jing's classical formulae for depression have been continuously expanded and deepened. This article reveals the rules of medication of the treatment of depression with ZHANG Zhong-jing's classical formulae from three aspects of Bupleurum class prescription， Gardenia class prescription， and other prescriptions， which is reflected in the study on the composition of prescription， the etiology， and pathogenesis and the symptoms of the treatment. Integrating and classifying ZHANG Zhong-jing's classical formulae's experience in the treatment of depression， mainly expounded from two aspects， clinical research and pharmacological research， summarizing the research perspective and progress of Zhongjing prescription medicine in the treatment of depression in recent years， to excavate， inherit and develop ZHANG Zhong-jing's classical formulae， and provide experience and reference for the treatment of depression from multiple angles and ideas.
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Objective: To evaluate the quality of Gardeniae Fructus from different producing areas and optimize the best place of production by using chemical pattern recognition method based on HPLC fingerprint and multi-component content determination. Methods: The RP-HPLC using acetonitrile-0.1% phosphoric acid aqueous solution as mobile phase based on the wavelength switching (234 nm and 440 nm) and gradient elution method was developed to evaluate the quality of 30 batches of Gardeniae Fructus from 10 different producing areas. The combination of chromatographic fingerprints and quality determination of five active ingredients, as well as chemometrics including hierarchical cluster analysis (HCA) and principal component analysis (PCA), were further employed for the quality assessment. Results: The fingerprint similarity of 30 batches of Gardeniae Fructus from 10 different producing areas were all above 0.95. The content ranges of deacetylated methyl oxalate, genipin gentiobioside, geniposide, crocin I, and crocin II were 0.61-4.26 mg/g, 1.73-12.92 mg/g, 51.79-82.76 mg/g, 5.03-12.80 mg/g, and 0.71-2.28 mg/g. Samples can be divided into three categories by HCA: The first category is Yongzhou in Hunan, Yong’ an in Hunan, Fengcheng in Jiangxi, Hukou in Jiangxi, Guangde in Anhui, and Fuding in Fujian; The second category is Lichuan in Jiangxi, Jurong in Jiangsu and Tanghe in Henan; And the third category is Lu’ an in Anhui. PCA was used to further evaluate the quality differences of the samples from different producing areas, and it was found that the medicinal materials from Lu’ an in Anhui, Hukou in Jiangxi, and Yong’ an in Hunan were of superior quality. Conclusion: The quality of Gardeniae Fructus from different producing areas was different to a certain extent, while the quality of same batches was stable. By combination of fingerprint and content determination, the chemical pattern recognition method can be used to evaluate the quality of the Gardeniae Fructus comprehensively. The establishment of this method provided an effective reference for the quality control and evaluation of Gardeniae Fructus.
ABSTRACT
Objective: To rapidly analyze chemical compositions in raw products and stir-fried products of Gardeniae Fructus,and determine the pharmacodynamic material basis of Gardeniae Fructus Praeparatus. Method: Liquid chromatography-ion trap-time-of-flight-mass spectrometry(LCMS-IT-TOF) was performed on ACQUITY UPLC HSS T3 column(2.1 mm×100 mm,1.8 μm),mobile phase was 0.005%formic acid aqueous solution(A)-acetonitrile(B) for gradient elution(0-5 min,10%-15%B;5-8 min,15%B;8-18 min,15%-95%B;18-20 min,95%B;20-22 min,95%-10%B;22-25 min,10%B),the column temperature was 30℃ and the flow rate was 0.4 mL·min-1,volume of sample injection was 2 μL;electrospray ionization(ESI) was applied for mass spectrometric analysis under positive and negative ion mode,the scanning ranges were m/z 100-1 000.The ion peaks were identified by comparison of control substances,mass spectrometry data analysis and literature references.The peak areas of some ion peaks before and after processing were compared,the changes of chemical compositions in Gardeniae Fructus after processing were investigated. Result: Based on the mass spectral data information and references,a total of 38 compounds were identified,no new compounds were produced after processing.The ion peak areas of main compounds were investigated during the stir-frying processing,the contents of geniposide,genipin-1-β-D-gentiobioside,shanzhiside,chlorogenic acid and crocin in Gardeniae Fructus Praeparatus were decreased;the contents of geniposidic acid and crocetin were increased. Conclusion: The method can rapidly and accurately identify the chemical constituents in Gardeniae Fructus Praeparatus.The changes of iridoids and crocins in Gardeniae Fructus during the stir-frying process may be related to hemostatic activity and protection of cardiovascular and cerebrovascular.
ABSTRACT
Ischemic stroke is one of the diseases that seriously threaten human health. It is characterized by the high morbidity, disability rate and mortality, and has been lacking effective treatment. Its occurrence is related to metabolic disorder, calcium overload, free radical injury, inflammatory reaction, etc. Gardeniae Fructus not only has antipyretic, analgesic, hepatoprotective and cholagogic effects, but also has protective effects against ischemic brain injury. At present, there are more studies about the main components of Gardeniae Fructus against ischemic brain injury, but the mechanism is unclear. In this paper, the mechanism of the main active ingredients from Gardeniae Fructus in the treatment of cerebral ischemia injury in recent years was reviewed, and the effective component monomer and the whole were analyzed, so as to provide a basis for the prevention and treatment of ischemic brain injury of Gardeniae Fructus decoction pieces, and provide a reference for further research and application of this decoction pieces.