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ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L-1）， Coptidis Rhizoma group（B group， 38.4 g·L-1）， processed Euodiae Fructus group（C group， 5.88 g·L-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（Cmax） of Ber， Pal， Evo， and Rut were the highest and time to peak（tmax） were the lowest in the liver of A group. In plasma， the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group， tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver， compared with B-D groups， Cmax values of 5 representative components except Pae were elevated， AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t1/2） of each representative components in A group was elevated and tmax was decreased， and Cmax of each representative ingredient except Pal was decreased， AUC0-t values of Ber and Pal were increased， whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.
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Objective:To explore the mechanism of Coptidis Rhizoma- Puerariae Lobamle Radix on the treatment of diabetic retinopathy (DR) and diabetic nephropathy (DN) by means of network pharmacology. Methods:The TCMSP and UniProt databases were used to retrieve the active components and targets of Coptidis Rhizoma and Puerariae Lobamle Radix. GeneCards and OMIM databases were used to search for DR and DN genes, and the online tool Venny was used to obtain intersection targets. Cytoscape 3.8.2 software was used to construct a network diagram of "components-targets", and the STRING platform was used to construct a protein interaction (PPI) network. GO function and KEGG pathway enrichment analysis were carried out through the DAVID annotation database. Molecular docking verification was performed. Results:A total of 18 active components and 74 disease-drug intersection targets were screened out from Coptidis Rhizoma- Puerariae Lobamle Radix. GO functional enrichment analysis showed that intersection targets were mainly concentrated in biological processes such as inflammation and apoptosis, involving cellular components such as extracellular space, plasma membrane, and cytoplasm, and was related to molecular functions such as protein binding, ATP binding, and enzyme binding. Enrichment analysis of KEGG revealed that the intersection target may be related to TNF signaling pathway, Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, etc. The results of molecular docking showed that the core component had a good binding energy with the core targets. Conclusion:Coptidis Rhizoma-Puerariae Lobamle Radix may regulate TNF signal pathway, Toll-like receptor signal pathway and PI3K/Akt signal pathway through TNF, IL6, TP53 and other targets, and play a role in inhibiting cell apoptosis, oxidative stress and reducing inflammation.
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ObjectiveTo explore the material basis of bile-processed Coptidis Rhizoma clearing excessive fire of liver-gallbladder based on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF/MS） metabolomics and molecular docking. MethodUPLC-Q-TOF/MS metabolomics was used to analyze the chemical constituents of Coptidis Rhizoma， water-processed Coptidis Rhizoma and bile-processed Coptidis Rhizoma. Chromatographic separation was achieved with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase in gradient elution（0-2 min， 5%B； 2-20 min， 5%-65%B； 20-40 min， 65%-10%B； 40-45 min， 10%B； 45-46 min， 10%-95%B； 46-49 min， 95%B）， and electrospray ionization（ESI） was applied and operated in positive and negative ion modes， the acquisition range was m/z 80-1 200. Based on this， partial least squares-discriminant analysis（PLS-DA） and variance analysis were used to screen the differential compounds among the three products of Coptidis Rhizoma. Network pharmacology and molecular docking were used to verify the degree of association between differential compounds and excessive fire of liver-gallbladder syndrome. ResultA total of 33 chemical constituents were identified， including 2 phenolic acids， 5 binding bile acids and 26 alkaloids. And 16 differential compounds were identified by multivariate statistical analysis， including 11 alkaloids and 5 binding bile acids. Pathway enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes（KEGG） database yielded 8 pathways related to excessive fire of liver-gallbladder， and the key protein phosphatidylinositol 4，5-bisphosphate 3-kinase catalytic subunit alpha isoform（PIK3CA） was obtained according to the "component-target-pathway" network analysis. Molecular docking results showed that 11 alkaloids had good binding ability with PIK3CA. ConclusionPorcine bile is unique in the processing of bile-processed Coptidis Rhizoma， which can promote the production and dissolution of 11 alkaloids， including berberine and dihydrochelerythrine. Based on the results of molecular docking and reported pharmacological experiments， it can be concluded that 16 different compounds such as berberine， dihydrochelerythrine and taurohyodeoxycholic acid are the material basis of bile-processed Coptidis Rhizoma.
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Scutellariae Radix， Coptidis Rhizoma， and Phellodendri Chinensis Cortex are three commonly used Chinese herbal medicines， and their application in classic famous prescriptions cannot be fully explained by the triple energizer classification method. This study reviewed the ancient materia medica works and elaborated on the functions of the three herbal medicines before the Song dynasty and after the Jin dynasty. The works before the Song dynasty mainly introduced the diseases treated by the three herbal medicines according to the Shennong's Classic of Materia Medica（《神农本草经》）， and the works after the Jin dynasty mainly expounded the indications of the three medicines in the Shennong's Classic of Materia Medica according to the new medical theory. Although all the three herbal medicines can treat heat syndrome， digestive system diseases， skin and mucosa diseases， they act on different targets. Scutellariae Radix can regulate Qi stagnation and reverse caused by the fire syndrome. Coptidis Rhizoma can treat excess fire and purulent bloody stool caused by the deficiency of Zang-fu organs. Phellodendri Chinensis Cortex mainly treats the diseases of the intestine and reproductive system and can kill parasites. In addition， this paper summarized the descriptions about the functions of Scutellariae Radix in eliminating blood blockage， Coptidis Rhizoma in protecting the intestine， and Phellodendri Chinensis Cortex in clearing the liver in ancient books. According to the sentences in the Treatise on Febrile and Miscellaneous Diseases（《伤寒杂病论》）， the application of Scutellariae Radix in Chaihu prescriptions， Coptidis Rhizoma in Baitouweng Decoction， and Phellodendri Chinensis Cortex in Zhizi Baipi Decoction confirms to the indications of the three medicines in the materia medica works before the Song Dynasty. The existing clinical and pharmacological research results confirm the indications of the three herbal medicines in the ancient works. The clinical application of the three medicines should refer to the materia medicia works before the Song dynasty， so as to achieve precise medication.
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Coptidis Rhizoma- Cinnamomi Cortex is a classic couplet medicine of Traditional Chinese Medicine, which has the function of communicating heart and kidney, and has been widely used in clinic. At present, the chemical composition of Coptidis Rhizoma- Cinnamomi Cortex before and after compatibility, in terms of nature, quality and in vivo processes to carry out research. The drug pair has sedative hypnotic, hypoglycemic, antidepressant, antiarrhythmic and other pharmacological effects, involving regulation of neurotransmitters, regulation of inflammatory cytokines, antioxidant, regulation of intestinal flora and other mechanisms. The existing research is still insufficient, such as the study on the changes of material basis after the compatibility of Coptidis Rhizoma- Cinnamomi Cortex, as well as the pharmacological effects of cardiovascular system, lipid metabolism and perimenopausal syndrome. The best compatibility ratio of Coptidis Rhizoma- Cinnamomi Cortex in sedation, hypnosis, hypoglycemic and antidepressant needs further analysis.
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Objective:To study the HPLC fingerprints of Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules and the differences of active ingredients in different proportions; To explore the content changes of key components in different proportions of Coptidis Rhizoma- Magnoliae Officmalis Cortex. Methods:HPLC was used to determine the contents of several alkaloids and total phenol of Magnolia officinalis in Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules and their fingerprints, and the similarity evaluation, cluster analysis and principal component analysis were performed. Results:The similarity of fingerprint of 10 batches of Coptidis Rhizoma- Magnoliae Officmalis Cortex was > 0.950. 17 common peaks were identified, and 6 components were identified. Compared with single medicine, the contents of alkaloids and total phenols in the Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules were significantly reduced. The contents of multiple alkaloids and total phenols in the Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules in different proportions were different, and the contents of alkaloids and total phenols were the highest when the proportion of Coptidis Rhizoma- Magnoliae Officmalis Cortex was 2∶1. Conclusion:The contents of main components of Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules with different proportions are different, which can provide a certain basis for studying the compatibility mechanism of TCM couplet medicines.
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ObjectiveTo analyze changes of the chemical composition in Euodiae Fructus before and after processing with Coptidis Rhizoma decoction， so as to provide scientific basis for elucidating the processing mechanism of this decoction pieces. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS） was performed on a Titank C18 column （2.1 mm×100 mm， 1.8 μm）， the mobile phase was 0.1% formic acid aqueous solution-acetonitrile for gradient elution， the column temperature was set at 40 ℃， the flow rate was 0.25 mL·min-1. Electrospray ionization （ESI） was used to scan in positive and negative ion modes， and the scanning range was m/z 50-1 250. The chemical constituents in Euodiae Fructus were identified before and after processing by reference substance comparison， database matching and literature reference， and MarkerView™ 1.2.1 software was used to normalize the obtained data， SIMCA-P 14.1 software was employed to perform principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） on MS data of raw and processed products to screen the differential components before and after processing. ResultA total of 50 compounds were identified， including 48 kinds of stir-fried products with Coptidis Rhizoma decoction and 44 kinds of raw products. After processing， six compounds were added， including danshensu， noroxyhydrastinine， oxyberberine， 13-methylberberrubine， protopine and canadine. However， two kinds of compounds， including （S）-7-hydroxysecorutaecarpine and wuchuyuamide Ⅱ， were not detected after processing. In general， after processing， the overall contents of phenolic acids and flavonoids decreased significantly， the overall content of limonoids increased， and the overall content of alkaloids did not decrease insignificantly. The results of PCA and OPLS-DA showed that there were significant differences in the composition and content of the chemical components of Euodiae Fructus before and after processing， and a total of 12 variables such as quercetin， dihydrorutaecarpine and dehydroevodiamine were obtained by screening. ConclusionEuodiae Fructus stir-fried with Coptidis Rhizoma decoction mainly contains phenolic acids， flavonoids， limonoids and alkaloids. The composition and content of the chemical components have some changes before and after processing. The addition of processing excipients and hot water immersion are the main reasons for the difference， which can provide experimental basis for interpretation of the processing mechanism of this characteristic processed products of Euodiae Fructus.
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ObjectiveTo explore the application law of compound prescriptions containing Coptidis Rhizoma to diabetes and its complications based on data mining. MethodA total of 288 records on formulas containing Coptidis Rhizoma in the treatment of diabetes and its complications and the corresponding syndromes and symptoms were retrieved from the medical records of modern physicians， with 218 on the treatment of diabetes and 70 on the treatment of diabetes complications. The Traditional Chinese Medicine Inheritance Computing Platform （V3.0） was used or data mining on the compositions of the formulas. Moreover， it was employed for the frequency statistics， formula analysis， symptom analysis， association rules analysis， network visualization， and cluster analysis. ResultThe 218 formulas containing Coptidis Rhizoma for the treatment of diabetes involved 190 Chinese medicinals. A total of 12 syndromes showed the occurrence frequency ≥ 6， and the one with the highest frequency was deficiency of both qi and yin， followed by the syndrome of excessive heat in lung and stomach， syndrome of Yin deficiency and effulgent fire， and syndrome of excessive heat and fluid consumption. The dose of Coptidis Rhizoma for the treatment of diabetes ranged from 1.5-30 g， and the most frequently used doses were 10， 6， and 5 g. The medicinal was frequently applied for the traditional Chinese medicine symptoms of dry stool， dry mouth and tongue， and swift digestion with rapid hungering. Moreover， 26 core medicinal pairs， 17 association rules， 3 diagrams on medicinal relationship， and 3 core combinations were yielded. The 70 formulas containing Coptidis Rhizoma for the treatment of diabetes complications involved 184 Chinese medicinals， and the top 3 complications were diabetic nephropathy， diabetic peripheral neuropathy， and diabetic gastroenteropathy. The dose of Coptidis Rhizoma in the treatment of diabetes complications fell in the range of 2-15 g， and 10， 6， and 5 g were most frequently used. ConclusionFormulas containing Coptidis Rhizoma for the treatment of diabetes and its complications mainly target the syndrome of dampness-heat transforming into fire and the syndrome of excessive heat damaging yin. This study can serve as a reference for standard use of Coptidis Rhizoma in the prevention and treatment of diabetes and its complications.
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Zuojinwan originated from Danxi′s Experiential Therapy （《丹溪心法》） in the Yuan dynasty. It is a representative prescription for the treatment of liver fire invading stomach syndrome， and is also one of the typical prescriptions of the anti-adjuvant method of traditional Chinese medicine （TCM）. In this paper， the method of bibliometrics was used to systematically sort out the ancient books of Zuojinwan， and 729 relevant literature data were obtained. After certain retrieval and screening， 57 ancient books of TCM were finally obtained. The statistics and analysis were carried out from the aspects of prescription source， historical evolution， composition， functions， evolution of prescription meaning， prescription dose， and preparation and usage of Zuojinwan. It was found that Zuojinwan was composed of Coptis chinensis rhizoma and Euodia rutaecarpa fructus in a ratio of 6∶1. It was mainly used for the treatment of liver fire invading stomach syndrome. The symptoms included pain in chest and hypochondrium， vomiting and bitter mouth， noisy acid-swallowing， red tongue coating yellow， and pulse string number. Later medical records recorded that Zuojinwan was mostly consistent with the original prescription. It mainly treated various diseases caused by liver fire， including left by liver fire， including left hypochondriac pain， swallowing acid and vomiting acid， tendon hernia and lump， epigastric pain， bitter mouth pulse string， head pain， diarrhea， gonorrhea， cold and hot， abdominal pain， alcohol wet yellowing， silence of oral dysentery and so on. There was little controversy in the analysis of relevant prescriptions. In the past dynasties， pills was mainly used， which was consistent with the original prescription. In modern times， it is mainly water flooding for pills or steamed cakes for pills， warm boiling water to serve 6 g， taking 2-3 g per time， the history is basically the same. In this paper， through the excavation， collation and systematic analysis of the ancient literature of TCM that recorded Zuojinwan， we hope to provide the literature basis for the development， inheritance and utilization of this famous classical formulas.
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ObjectiveTo investigate the synergistic effect of Coptidis Rhizoma crude polysaccharide （CCP） and berberine （BBR） in treating ulcerative colitis （UC） model mice. MethodThirty male BALB/c mice were randomized into five groups. Except the 6 mice in the normal group， the rest were given 5% dextran sodium sulfate in their daily drinking water to establish the UC model. After modeling， the mice were administrated with corresponding agents by gavage once daily for 4 days： BBR （100 mg·kg-1） group， BBR （100 mg·kg-1） + low-dose （22.8 mg·kg-1） CCP group， BBR （100 mg·kg-1） + high-dose （45.6 mg·kg-1） CCP group. The mice in the model group and normal group were administrated with the same volume of normal saline. At the end of the experiment， the mice were sacrificed for the collection of colon， and the expression of tight junction proteins zonula occluden-1 （ZO-1）， Claudin-1， and Occludin in colon tissue was detected by Western blot. With the normal group as the control， the disease activity index （DAI） score， colon length， colon histomorphology， and expression levels of tight junction proteins in other groups were evaluated. ResultCompared with the normal group， the modeling down-regulated the protein levels of ZO-1， Claudin-1， and Occludin （P<0.01）. Compared with the model group， BBR did not significantly change the protein level of Claudin-1 and up-regulated those of ZO-1 and occludin （P<0.01）. The expression levels of Claudin-1， ZO-1， and Occludin were up-regulated in BBR + CCP groups （P<0.01）. The expression levels of tight junction proteins in BBR + CCP groups were significantly higher than those in the BBR group （P<0.05）. ConclusionThe administration of CCP combined with BBR can effectively ameliorate intestinal mucosal barrier damage in the mice with UC.
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Herb pair， a common form of compounding in Chinese medicinal prescriptions， reflects the experience of pharmacists in clinical medication in the past. It is characterized by simple composition while has the basic characteristics of Chinese medicine compounding. The combination of two medicinal herbs can enhance effect or reduce toxicity. Coptidis Rhizoma （CR） has the effects of clearing heat， drying dampness， purging fire， and removing toxin. Euodiae Fructus （EF） is acrid， bitter， and hot-natured， which can not only warm the Yang Qi in spleen and stomach to dissipate cold and relieve pain， but also descend stomach Qi and prevent vomiting. Furthermore， it can warm the liver and kidney. CR and EF form a typical cold-heat herb pair， which oppose and yet also complement each other. Specifically， their cold and heat natures interact with each other to clear liver fire， harmonize stomach for descending adverse Qi， relieve depression， and dissipate mass. CR clears the intestine and stops dysentery， while EF warms the middle and promotes the circulation of Qi. The combination of them can thus clear heat， dry dampness， and relieve pain. Modern pharmacological studies have demonstrated that CR-EF has not only significant efficacy against digestive system diseases but also good anti-cancer， anti-inflammatory， anti-ulcer， and lipid-lowering activities. Therefore， the article summarized the effect enhancement and toxicity reduction of the herb pair at the levels of cellular molecule， isolated organ， and whole animal， and clarified the mechanism of its pharmacological action. It will provide a theoretical basis for further development and clinical use of the herb pair.
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Through the combing of ancient books of Chinese herbal medicine in the past dynasties， a textual research of Coptidis Rhizoma involved the name， origin， medicinal parts， producing area， quality evaluation， harvesting and processing methods in famous classical formulas was conducted in this paper. After textual research， the mainstream varieties of Coptidis Rhizoma in the Ranunculaceae family before Tang and Song dynasties were Coptis chinensis and C. chinensis var. brevisepala， after the Ming and Qing dynasties， C. deltoidea， C. teeta and C. omeiensis were gradually praised. In ancient times， the authentic producing area of Coptidis Rhizoma has the characteristics of gradually moving to the west. The eastern Coptidis Rhizoma was highly praised in the early stage， while in the later stage， western Coptidis Rhizoma like chicken feet was highly praised. In the early stage， western Coptidis Rhizoma probably originated from C. chinensis and its genus， while Coptidis Rhizoma like chicken feet was cultivated， and no wild species has been found so far. As Coptidis Rhizoma has mixed use of multiple origins in ancient books of past dynasties， based on the current shortage of market resources in C. teeta and C. deltoidea， there are also endangered and protected plants of C. chinensis var. brevisepala and C. omeiensis， combined with the mainstream medicines and resources of past generations， it is recommended to choose C. chinensis as the base of the formulas. In ancient times， there were many processing methods for Coptidis Rhizoma， such as frying and wine-， ginger-， honey-processed. In the process of developing famous classical formulas， the appropriate processing specifications of Coptidis Rhizoma should be selected based on the original source records and the requirements of the medicinal material.
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Objective: To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying. Methods: The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results: SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion: SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.
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Coptidis Rhizoma, as a bulk medicinal material, is in great demand in clinical practice. Its quality is uneven in the market due to the mixture of genuine, counterfeit and adulterants. Therefore, it is particularly important to establish a quality control system for Coptidis Rhizoma. Based on the concept of Chinese medicine quality marker(Q-marker), the potential quality markers of Coptidis Rhizoma were analyzed and predicted from the perspective of chemistry and pharmacology. The sources of the Q-markers of Coptidis Rhizoma were identified by literature retrieval. The potential Q-markers were then screened through the visualization of the "components-targets-pathways" network. High performance liquid chromatography(HPLC) was used to establish a multi-indicator qualitative and quantitative control method featuring fingerprints for 10 batches of Coptidis Rhizoma. A supervised mode of orthogonality partial least squares method-discriminant analysis(OPLS-DA) was used to screen the main marker components that caused differences between groups. The literature review results showed that the alkaloids were the main source of Coptidis Rhizoma Q-markers.The fingerprints of 13 common peaks were successfully established, and berberine, palmatine, berberine and epiberberine were selected as Q-markers of Coptidis Rhizoma, and their contents were determined.Based on the concept of the Q-marker of traditional Chinese medicine, the four components can be selected as the Q-marker of Coptidis Rhizoma after comprehensive consideration. The results of this study are not only conducive to the quality evaluation of Coptidis Rhizoma on the market, but also provide a reference for the overall quality control of Coptidis Rhizoma and lay foundation for the future exploration of the mechanism of Coptidis Rhizoma.
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Alkaloids , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Multivariate Analysis , RhizomeABSTRACT
Objective::To identify the main active components of Coptidis Rhizoma and Euodiae Fructus for the treatment of gastric cancer, predict the targets of the common active components in these two herbs, establish the network of active drug components-target genes, and further explore the potential mechanism and effect of Coptidis Rhizoma-Euodiae Fructus for the treatment of gastric cancer. Method::The active components of Coptidis Rhizoma-Euodiae Fructus were screened by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), gastric cancer targets were predicted and screened by Genecard database platform, " drug-active ingredient-disease-targets" networks were built by Cytoscape (3.7.1) software, and protein interaction networks were built by String database platform. Finally, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Bioconductor platform and R language. Result::The 14 potential active components of Coptidis Rhizoma and 15 potential active components of Euodiae Fructus were obtained, involving 127 targets related to gastric cancer. There were 33 common targets for Coptidis Rhizoma-Euodiae Fructus-gastric cancer, which played a therapeutic role in gastric cancer mainly by regulating target genes such as PTGS2, PTGS1, AR, RXRA and NOS2, as well as cell apoptosis, p53 signaling pathway and interleukin (IL)-17 signaling pathway. Conclusion::The therapeutic mechanism of Coptidis Rhizoma-Euodiae Fructus reflects the multi-component, multi-target and multi-pathway characteristics of traditional Chinese medicines and provides the scientific basis for further study and the material basis of Coptidis Rhizoma-Euodiae Fructus against gastric cancer.
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OBJECTIVE：To provide refere nce f or the quality control and evaluation of rice-wine processed Coptidis Rhizoma decoction piece. METHODS ：Taking 17 batches of rice-wine processed Coptidis Rhizoma decoction piece from different manufacturers as samples ，HPLC method was adopted to determine the contents of 4 kinds of alkaloids as epiberberine ，coptisine， palmatine and berberine. The compound weights of epiberberine ，berberine，palmatine and berberine were calculated by the subjective and objective combination weighting method （AHP combined with variation coefficient ）. Then the quality evaluation method was used to evaluate the quality of decoction pieces combined with the appearance of decoction pieces and the contents of 4 alkaloids. The percent mass constant was calculated and the grade of rice-wine processed Coptidis Rhizoma decoction piece was classified. RESULTS ：According to the results of content determination of 4 kinds of alkaloids ，among 17 batches of samples ，a total of 13 batches of samples met the requirements of 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. Mass constants of 13 batches of qualified samples were 10.03-26.96，and the percent mass constants were 37.20％-100％. If the percent mass constant ≥ 80％ of the sample was listed as the first-class product ，the sample with the percent mass constant between 50％-＜80％ was classified as the second-class product ，and the rest was listed as the third-class product ，therefore the quality constant of first-class product was ≥21.57，that of second-class product was 13.48-＜21.57，and that of third-class product was ＜13.48. According to the grading standard ，3 batches of 13 batches of qualified samples are classified as first-class products ，6 batches are classified as second-class products ，4 batches are classified as third-class products. CONCLUSIONS ：The established subjective and objective combination weighting method and quality constant method can more scientifically and reasonably classify rice-wine processed Coptidis Rhizoma decoction piece.
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Objective: To clarify the characteristics of drug pair of Coptidis Rhizoma-Euodiae Fructus on multi-components, multi-targets and multi-pathways based on the network pharmacology, and provide a theoretical reference for further study on the pharmacodynamic basis and mechanism of Coptidis Rhizoma-Euodiae Fructus against cancer and cardio-cerebrovascular diseases. Methods: Through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the parameters of oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18) combined with the biological function, contents, research hotspot and other factors were used to screen out the active ingredients of the medicine pair of Coptidis Rhizoma - Euodiae Fructus. DrugBank and TCMSP databases were used to predict and analyze the targets, and Uniprot database was used to sort out all relevant genes affecting the targets. Combining the KEGG database for GO analysis and pathway analysis, "ingredients-targets-related diseases" network was constructed using Cytoscape software. Results: A total of 41 compounds and 212 potential target genes, as well as 44 signaling pathways were obtained after screening from Coptidis Rhizoma-Euodiae Fructus, and there were 44 major signaling pathways involved in 30 pathways related to cancer, seven pathways which were related to cardio-cerebrovascular diseases, seven pathways which were related to cancer and cardio-cerebrovascular diseases. Conclusion: The active ingredients of Coptidis Rhizoma-Euodiae Fructus can up-regulate the expression of cancer apoptosis genes through multi-components, multi-targets and multi-pathways, down-regulate the expression of cell cycle and apoptosis-related genes, and produce anti-cancer effect; Protecting vascular cells by inhibiting vascular calcification, and to achieve the effect of treating cardio-cerebrovascular diseases by inhibiting apoptosis and proliferation.
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Objective: HPLC fingerprints of Banxia Xiexin Decoction (BXD) was established to analyze the quality value transmitting relationship between medical herbs-decoction pieces-whole decoction of Scutellariae Radix (SR) and Coptidis Rhizoma (CR). Methods: BXD was prepared by the decoction method recorded in Treatise on Febrile Diseases. BXD HPLC fingerprints was established, and the characteristic peaks were analyzed; The transfer rate, the dry extract rate and the similarity of fingerprint were used as indicators to analyze the quality value transmitting relationship between medical herbs-decoction pieces-whole decoction of SR and CR. Results: The transfer rate of baicalin from medical herbs to decoction pieces was between 81.08% and 119.82%; The transfer rate of baicalin from decoction pieces to BXD was between 44.55% and 59.05%; The transfer rate of berberine from medical herbs to decoction pieces was between 66.65% and 97.51%; The transfer rate of berberine from decoction pieces to BXD was between 7.83% and 22.93%; And the dry extract rate of the whole decoction was between 12.99% and 17.21%. The similarity of fingerprints of 15 batches of BXD ranged from 0.978 to 0.999. Conclusion: The quality evaluation method established by the fingerprint is applicable to the quality control of medical herbs-decoction pieces-whole decoction of SR and CR, which provides some reference for the establishment of the quality evaluation method of famous classic formula.
ABSTRACT
Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitterness components, multi-component bitterness superposition and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitterness components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids(bamatine, jatrorrhizine, berberine, epiberberine and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on the decoction of Coptidis Rhizoma and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on the decoction of Coptidis Rhizoma and five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the butter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.
Subject(s)
Humans , Alkaloids , Coptis , Drugs, Chinese Herbal , Molecular Docking Simulation , Structure-Activity Relationship , TasteABSTRACT
Objective:Based on UPLC-Q-Orbitrap HRMS and network pharmacology, the material basis, processing principle and molecular mechanism of bile processed Coptidis Rhizoma (BPRC) for reducing excess fire of liver and gallbladder were elucidated.Method:The chemical ingredients of BPRC were analyzed by UPLC-Q-Orbitrap HRMS. Chromatographic separation was achieved with 0.1% formic acid solution (A)-acetonitrile (B) as the mobile phase in gradient elution (0-20 min, 5%-80%B; 20-30 min, 80%-95%B; 30-30.1 min, 95%-5%B; 30.1-35 min, 95%-5%B). The flow rate was 0.2 mL·min-1, electrospray ionization (ESI) was applied and operated in positive and negative ion modes, the acquisition range was m/z 100-1 500. Based on the clinical manifestations and pathogenic factors of excess fire of liver and gallbladder, the potential effective ingredients, targets and functional characteristics of BPRC were predicted and analyzed by online database. Based on the characteristics of the new active ingredients after processing, the processing principle of BPRC was investigated by network pharmacology.Result:A total of 19 ingredients in BPRC were identified, six of which were newly added cholic acids after processing. It was determined that the alkaloids, including worenine, epiberberine, jatrorrhizine, coptisine, berberrubine, berberine, palmatine and cholic acids, including glycohyodeoxycholic acid, taurohyodeoxycholic acid, glycochenodeoxycholic acid, hyodeoxycholic acid and taurochenodeoxycholic acid, were identified as material basis of BPRC. A total of 66 targets of reducing excess fire of liver and gallbladder of BPRC were screened. There were 16 common targets and multiple same signaling pathways between cholic acids and alkaloids of BPRC, and many lesions of excess fire of liver and gallbladder were target organs of cholic acids. By acting on some targets, including albumin (ALB), Caspase-3 (CASP3), mitogen-activated protein kinase 14 (MAPK14), glucocorticoid receptor (NR3C1) and other targets and some signaling pathways, including interleukin (IL)-17, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), MAPK and other pathways, BPRC could reduce excess fire of liver and gallbladder.Conclusion:BPRC has the characteristics of multi-component, multi-target and multi-pathway on reducing excess fire of liver and gallbladder. Bile and Coptidis Rhizoma have synergistic effect and bile can enhance the intensity of BPRC in lesions, which confirms the processing theory that the effect of BPRC on excess fire of liver and gallbladder enhance after being processed by bile.