Mechanism of action of Coptidis Rhizome in treating periodontitis based on network pharmacology and in vitro validation.

OBJECTIVE: Explore the therapeutic mechanism of Coptidis Rhizome (CR) in periodontitis using network pharmacology, and validate it through molecular docking and in vitro experiments. METHODS: Screened potential active components and target genes of CR from TCMSP and Swiss databases. Identified periodontitis-related target genes using GeneCards. Found common target genes using Venny. Conducted GO and KEGG pathway analysis. Performed molecular docking and in vitro experiments using Berberine, the main active component of CR, on lymphocytes from healthy and periodontitis patients. Assessed effects on inflammatory factors using CCK-8, flow cytometry, and ELISA. RESULTS: Fourteen active components and 291 targets of CR were identified. 30 intersecting target genes with periodontitis were found. GO and KEGG analysis revealed oxidative stress response and IL-17 signaling pathway as key mechanisms. Molecular docking showed strong binding of Berberine with ALOX5, AKT1, NOS2, and TNF. In vitro experiments have demonstrated the ability of berberine to inhibit the expression of Th17 + and other immune related cells in LPS stimulated lymphocytes, and reduce the secretion of IL-6, IL-8, and IL-17. CONCLUSION: CR treats periodontitis through a multi-component, multi-target, and multi-pathway approach. Berberine, its key component, acts through the IL-17 signaling pathway to exert anti-inflammatory effects.

Coptidis rhizoma extract alleviates oropharyngeal candidiasis by gC1qR-EGFR/ERK/c-fos axis-induced endocytosis of oral epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis rhizoma, first recorded in the "Shen Nong's Herbal Classic", is one of the traditional Chinese medicine (TCM) used to treat infectious diseases, with reputed effectiveness against oropharyngeal candidiasis (OPC). Studies have demonstrated the inhibitory properties of C. rhizoma (CRE) against Candida albicans, yet there is limited information available regarding its treatment mechanism for OPC. AIM OF THE STUDY: Our previous research has suggested that CRE can prevent the formation of C. albicans hyphae and their invasion of the oral mucosa, thereby exerting a therapeutic effect on OPC. Nevertheless, the precise therapeutic mechanisms remain incompletely understood. Previous studies have revealed that a receptor for globular heads of C1q (gC1qR), a crucial co-receptor of the epidermal growth factor receptor (EGFR), facilitates the EGFR-mediated internalization of C. albicans. Therefore, this study aims to investigate the potential mechanism of action of CRE and its primary component, berberine (BBR), in treating OPC by exploring their effects on the gC1qR-EGFR co-receptor. MATERIALS AND METHODS: To identify the chemical components of CRE, we utilized Ultra-high performance liquid chromatography in conjunction with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MSE), revealing the presence of at least 18 distinct components. To observe the therapeutic effects of CRE on OPC at the animal level, we employed hematoxylin and eosin staining, periodic acid-Schiff staining, scanning electron microscopy, and fungal load detection. Subsequently, we evaluated the anti-inflammatory properties of CRE and its main component, BBR, in treating OPC. This was achieved through enzyme-linked immunosorbent assay (ELISA) both at the animal and cellular levels. Additionally, we assessed the ability of C. albicans to disrupt the epithelial barrier of FaDu cells by studying the protective effects of BBR on the fusion barrier using the transwell assay. To further explore the underlying mechanisms, we analyzed the effects of BBR on the gC1qR-EGFR/extracellular signal-regulated kinase/c-Fos signaling pathway at the cellular level using qRT-PCR, western blotting, and immunofluorescence. Furthermore, we validated the effects of BBR on the gC1qR-EGFR co-receptor through ELISA, qRT-PCR, and western blotting. Finally, to confirm the outcomes observed at the cellular level, we validated the impact of CRE on the gC1qR-EGFR co-receptor in vivo using qRT-PCR, western blotting, and immunofluorescence. These comprehensive methods allowed us to gain a deeper understanding of the therapeutic mechanisms of CRE and BBR in treating OPC. RESULTS: Our findings indicate that CRE and its primary component, BBR, effectively alleviated the symptoms of OPC by modulating the gC1qR-EGFR co-receptor. The chemical composition of CRE and BBR was accurately identified using UPLC-Q/TOF-MSE. The gC1qR-EGFR co-receptor plays a crucial role in regulating downstream signaling pathways, emerging as a potential therapeutic target for OPC treatment. Through both in vitro and in vivo experiments, we explored the therapeutic potential of CRE and BBR in OPC. Additionally, we employed overexpression and silencing techniques to confirm that BBR can indeed influence the gC1qR-EGFR co-receptor and regulate the gC1qR-EGFR/extracellular signal-regulated kinase (ERK)/c-Fos signaling pathway, leading to improved OPC outcomes. Furthermore, the significance of CRE's effect on the gC1qR-EGFR co-receptor was validated in vivo. CONCLUSION: Our study demonstrates that CRE and its main component, BBR, can effectively alleviate OPC symptoms by targeting the gC1qR-EGFR heterodimer receptor. This discovery offers a promising new therapeutic approach for the treatment of OPC.

Exploring active ingredients and mechanisms of Coptidis Rhizoma-ginger against colon cancer using network pharmacology and molecular docking.

BACKGROUND: Colon cancer is the most prevalent and rapidly increasing malignancy globally. It has been suggested that some of the ingredients in the herb pair of Coptidis Rhizoma and ginger (Zingiber officinale), a traditional Chinese medicine, have potential anti-colon cancer properties. OBJECTIVE: This study aimed to investigate the molecular mechanisms underlying the effects of the Coptidis Rhizoma-ginger herb pair in treating colon cancer, using an integrated approach combining network pharmacology and molecular docking. METHODS: The ingredients of the herb pair Coptidis Rhizoma-ginger, along with their corresponding protein targets, were obtained from the Traditional Chinese Medicine System Pharmacology and Swiss Target Prediction databases. Target genes associated with colon cancer were retrieved from the GeneCards and OMIM databases. Then, the protein targets of the active ingredients in the herb pair were identified, and the disease-related overlapping targets were determined using the Venn online tool. The protein-protein interaction (PPI) network was constructed using STRING database and analyzed using Cytoscape 3.9.1 to identify key targets. Then, a compound-target-disease-pathway network map was constructed. The intersecting target genes were subjected to Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for colon cancer treatment. Molecular docking was performed using the Molecular Operating Environment (MOE) software to predict the binding affinity between the key targets and active compounds. RESULTS: Besides 1922 disease-related targets, 630 targets associated with 20 potential active compounds of the herb pair Coptidis Rhizoma-ginger were collected. Of these, 229 intersection targets were obtained. Forty key targets, including STAT3, Akt1, SRC, and HSP90AA1, were further analyzed using the ClueGO plugin in Cytoscape. These targets are involved in biological processes such as miRNA-mediated gene silencing, phosphatidylinositol 3-kinase (PI3K) signaling, and telomerase activity. KEGG enrichment analysis showed that PI3K-Akt and hypoxia-inducible factor 1 (HIF-1) signaling pathways were closely related to colon cancer prevention by the herb pair Coptidis Rhizoma-ginger. Ten genes (Akt1, TP53, STAT3, SRC, HSP90AA1, JAK2, CASP3, PTGS2, BCl2, and ESR1) were identified as key genes for validation through molecular docking simulation. CONCLUSIONS: This study demonstrated that the herb pair Coptidis Rhizoma-ginger exerted preventive effects against colon cancer by targeting multiple genes, utilizing various active compounds, and modulating multiple pathways. These findings might provide the basis for further investigations into the molecular mechanisms underlying the therapeutic effects of Coptidis Rhizoma-ginger in colon cancer treatment, potentially leading to the development of novel drugs for combating this disease.

Huang Lian Jie Du Decoction enhances the anti-tumor efficacy of immune checkpoint inhibitors by activating TLR7/8 signalling in melanoma.

BACKGROUND: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. METHODS: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. RESULTS: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors. CONCLUSIONS: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.

Protective Effects of Coptis chinensis Rhizome Extract and Its Constituents (Berberine, Coptisine, and Palmatine) against α-Synuclein Neurotoxicity in Dopaminergic SH-SY5Y Cells.

Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in ß-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37-11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.

Mechanism of the components compatibility of Scutellariae Radix and Coptidis Rhizoma on mice with hyperlipidemia by regulating the Cyp4a family.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (Scutellariae Radix, SR) and Coptis chinensis Franch (Coptidis Rhizoma, CR) is a classic herbal pair used in many Traditional Chinese Medicine formulations in the treatment of hyperlipidemia (HLP). As effective ingredients of the drug pair, the effects and mechanisms of berberine and baicalin in the treatment of HLP in the form of components compatibility are still unclear. AIM OF THE STUDY: To explore the mechanism of the components compatibility of SR and CR in the treatment of HLP. MATERIALS AND METHODS: The HLP model was established by a high-fat diet. Serum biochemical indexes were detected. Transcriptomics and metabolomics were detected. RT-PCR and Western Blot were used to analyze the effect of RA on the expression of the Cyp4a family during the treatment of HLP. RESULTS: Berberine-baicalin (RA) has a good effect in the treatment of HLP. RA can significantly reduce the body weight and liver weight of HLP, reduce the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), and increase the level of high-density lipoprotein (HDL-C). Through transcriptomic analysis, RA significantly reversed the gene expression of Cyp4a10, Cyp4a12 b, Cyp4a31, and Cyp4a32 in cytochrome P450 family 4 subfamily a (Cyp4a) which related to fatty acid degradation in the liver of HLP mice. The results of fatty acid detection showed that RA could significantly regulate heptanoic acid, EPA, adrenic acid, DH-γ-linolenic acid, and DPA in the cecum of HLP mice. The Cyp4a family genes regulated by RA are closely related to a variety of fatty acids regulated by RA. RT-PCR confirmed that RA could regulate Cyp4a mRNA expression in HLP mice. WB also showed that RA can regulate the protein expression level of Cyp4a. CONCLUSION: The components compatibility of SR and CR can effectively improve the blood lipid level of HLP mice, its mechanism may be related to regulating Cyp4a gene expression and affecting fatty acid degradation, regulating the level of fatty acid metabolism in the body.

The Mechanism of Polygonum Hydropiper L-Coptis Chinensis in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Validation.

BACKGROUND: Polygonum hydropiper L (PH) was widely used to treat dysentery, gastroenteritis, diarrhea and other diseases. Coptis chinensis (CC) had the effects of clearing dampness-heat, purging fire, and detoxifying. Study confirmed that flavonoids in PH and alkaloids in CC alleviated inflammation to inhibit the development of intestinal inflammation. However, how PH-CC affects UC was unclear. Therefore, the aim of this study is to analyze the mechanism of PH-CC on ulcerative colitis (UC) through network pharmacology and in vivo experiments. METHODS: The active ingredients and targets of PH-CC and targets of UC were screened based on related databases. The core targets of PH-CC on UC was predicted by protein-protein interaction network (PPI), and then the Gene Ontology-biological processes (GO-BP) function enrichment analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. The binding activity between pyroptosis proteins, core targets and effective ingredients were verified based on molecular docking technology. Finally, combined with the results of network pharmacology and literature research, the mechanism of PH-CC against UC was verified by in vivo experiments. RESULTS: There were 23 active components and 191 potential targets in PH-CC, 5275 targets in UC, and 141 co-targets. GO-BP functional analysis of 141 co-targets showed that the first 20 biological processes were closely related to inflammation and lipopolysaccharide (LPS) stimulation. Furthermore, core targets had good binding activity with the corresponding compounds. Animal experiment indicated that PH-CC effectively prevented weight loss in UC mice, reduced the disease activity index (DAI) score, maintained colon length, suppressed myeloperoxidase (MPO) activity, inhibited pyroptosis protein expression, and downregulated the levels of IL-18 and IL-1ß to alleviate intestinal inflammation. CONCLUSIONS: The results of network pharmacology and animal experiments showed that PH-CC suppressed the inflammatory response, restored colon morphology, and inhibited pyroptosis in UC mice. Thus, PH-CC may improve UC by regulating the NOD-like receptor protein domain 3 (NLRP3)/Caspase-1 signaling pathway.

Advancing green extraction of bioactive compounds using deep eutectic solvent-based ultrasound-assisted matrix solid-phase dispersion: Application to UHPLC-PAD analysis of alkaloids and organic acids in Coptidis rhizoma.

The utilization of deep eutectic solvents (DES) in sustainable extracting and separating of phytochemicals shows promising prospect. An exceptionally fast, eco-friendly, and sustainable approach was proposed for extracting bioactive compounds from Coptidis Rhizoma based on deep eutectic solvent-based ultrasound-assisted matrix solid phase dispersion (DES-UA-MSPD). Single-factor experiments and Box-Behnken design were utilized to explore the optimal extraction conditions. The analysis indicated that the acidic DES, especially betaine-acrylic acid (Bet-Aa 1:4 mol/mol) with 50% water content, was proved to be the most effective medium for the extraction of alkaloids (magnoflorine, groenlandicine, coptisine, epiberberine, berberine and palmatine) and organic acid (chlorogenic acid). With the parameters optimized, the total maximum extraction yield of alkaloids and organic acids reached 128.83 mg g-1 applying the optimal DES, which was 1.33-5.33 folds higher than conventional extraction solvents. Additionally, through microstructure analysis using scanning electron microscopy, density functional theory , and frontier molecular orbitals theory, a deeper understanding of the extraction principle was gained, and the molecular mechanism of DES synthesis and the interactions between target compounds were systematically elucidated. The sustainable and green potential of the DES-UA-MSPD method was demonstrated through Green Analytical Procedure Indexanalysis. The overall results of this investigation revealed that the proposed technology was a highly promising and sustainable alternative for effective extraction and quantification of natural products.

A network pharmacology method explores the molecular mechanism of Coptis chinensis for the treatment of Alzheimer's disease.

To predict the molecular mechanisms of action of Coptis chinensis in the treatment of Alzheimer's disease using network pharmacology. The active ingredients and targets of Coptis chinensis were obtained from the Traditional Chinese Medicine System Pharmacology Database. Target information for Alzheimer's disease was screened using the GeneCard and OMIM databases. The Venn diagram tool was used to identify the intersecting targets of Coptis chinensis and Alzheimer's disease. The obtained target information was entered into the STRING database to construct a protein-protein interaction network. The R language was used to perform Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of significant targets. Auto Dock Vina software was used for molecular docking. Fourteen effective active ingredients and 158 key targets associated with Coptis chinensis were identified. There were 1113 targets related to Alzheimer's disease genes. A drug-component-disease-target network was constructed and 84 key targets were identified for the treatment of Alzheimer's disease by Coptis chinensis. The main signaling pathways were the PI3K-Akt, AGE-RAGE, MAPK, HIF-1, TNF, and relaxin signaling pathways. The molecular docking results showed that berberine has a high affinity for Alzheimer's Disease. Coptis chinensis could play a multi-target and multi-pathway role against Alzheimer's disease, which has guiding significance for clinical research.

Transcriptome analysis reveals cadmium exposure enhanced the isoquinoline alkaloid biosynthesis and disease resistance in Coptis chinensis.

Coptis chinensis Franch is a perennial herb from the Ranunculaceae family with a long history of medicinal use. As the medicinal part, the rhizome of coptis often accumulates excessive cadmium (Cd) even at low concentrations in the soil, which not only compromises its medicinal safety but also raises concerns about adverse effects on human health. Therefore, effective strategies are needed to mitigate this accumulation and ensure its safe use in traditional medicine. This study utilized transcriptome profiling and physiological analysis to explore molecular mechanisms associated with ecological significance and the active accumulation of Cd in C. chinensis. The response to Cd in C. chinensis was assessed through RNA sequencing, Cd determination and isoquinoline alkaloid measurement using its roots, stems, and leaves. The transcriptome revealed, a total of 2667, 2998, or 2815 up-regulated deferentially expressed genes in roots, stems or leaves in response to Cd exposure. Furthermore, we identified phenylpropanoid and isoquinoline alkaloid biosynthesis as the key pathways response to Cd exposure, which suggests that C. chinensis may improve its tolerance to Cd through regulating the phenylpropanoid biosynthesis pathway. Under Cd exposure, plant-pathogen interaction in leaves was identified as the key pathway, which indicates that upregulation of genes involved in plant-pathogen interaction could enhance disease resistance in C. chinensis. WGCNA analysis identified WRKY8 (Cluster-55763.31419) and WRKY47 (Cluster-55763.221590) as potential regulators of secondary metabolic synthesis and plant-pathogen interaction pathway in C. chinensis triggered by Cd. The measurement of berberine, coptisine, palmatine, and epiberberine also demonstrated that Cd simulated the four isoquinoline alkaloids in roots. Therefore, our study not only presented a transcriptome expression profiles that revealed significant upregulation of genes involved in metal transport and detoxification pathways but also suggested a possible mechanism to cope with Cd accumulation. This knowledge provides a new insight into gene manipulation for controlling Cd accumulation, enhancing resistance and promoting synthesis of secondary metabolites with potential medicinal properties in other medicinal plant species.

A rapid localization and analysis method for isoquinoline alkaloids with fluorescence in Coptis chinensis Franch. By fabricating the nano-silver sol as a substrate for surface-enhanced Raman spectroscopy.

BACKGROUND: The quality of traditional Chinese medicines (TCMs) directly impacts their clinical efficacy and drug safety, making standardization a critical component of modern TCMs. Surface-enhanced Raman spectroscopy (SERS) is an effective physical detection method with speed, sensitivity, and suitability for large sample analyses. In this study, a SERS analysis method was developed using a nano-silver sol as the matrix to address the interference of fluorescence components in TCMs and overcome the limitations of traditional detection methods. RESULTS: The higher sensitivity and efficiency of SERS was used, enabling detection of a single sample within 30 s. Coptis chinensis Franch. (CCF) was chosen as the model medicine, the nano-silver sol was used as the matrix, and CCF's fourteen main fluorescent alkaloids were tested as index components. Typical signal peaks of the main components in CCF corresponded to the bending deformation of the nitrogen-containing ring plane outer ring system, methoxy stretching vibration, and isoquinoline ring deformation vibration. Through SERS detection of different parts, the distribution content of the main active components in the cortex of CCF was found to be lower than that in the xylem and phloem. Additionally, rapid quality control analyses indicated that among the nine batches of original medicinal materials purchased from Emei and Guangxi, the main active ingredient showed a higher content. SIGNIFICANCE: A SERS-based method for the rapid localization and analysis of multiple components of TCMs was established. The findings highlight the potential of SERS as a valuable tool for the analysis and quality control of TCMs, especially for fluorescent components.

Primary study on the effects and mechanisms of separate and combined decoctions of Scutellaria baicalensis Georgi - Coptis chinensis Franch extracts in relieving acute alcoholic liver injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SBG) and Coptis chinensis Franch (CCF) are traditional herbal medicine pairs used for clearing heat and eliminating dampness, stopping diarrhea, and detoxification. Traditionally, these two herbs are combined and decocted together, but the modern preparation procedures separate them to avoid the large amount of precipitation generated from co-decoction. Thus, a conflict lies between the traditional and modern extraction processes of Scutellaria baicalensis Georgi - Coptis chinensis Franch (SBG-CCF). AIM OF STUDY: There is a conflict between traditional medical practices of SBG-CCF and the modern formulation industry. In this study, we investigated the differences in the effects and mechanisms of SBG-CCF extracted by decocting separately and combining decoctions, as well as the scientific effectiveness of traditional and modern treatment methods on both. Acute alcoholic liver injury (ALI) rats were used as the pathological model. MATERIALS AND METHODS: SD rats were divided into 8 groups, including blank group, model group, low, medium, and high dose groups of SBG-CCF separated decoction, low, medium, and high dose groups of SBG-CCF combined decoction. Acute alcoholic liver injury model was induced in rats by gradually increasing the dose of alcohol through gavage everyday using white wine with an alcohol content 52%. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) were used as indicators to assess the intervention effect of SBG-CCF. And the potential active ingredients of SBG-CCF and the targets related to ALI were screened using network pharmacology, and the prediction results of network pharmacology were verified by quantitative real-time fluorescence PCR (qRT-PCR). RESULTS: SBG-CCF decoction alone and six combinations of decoctions have different degrees of improvement on alcoholic liver injury, with significant efficacy in the middle-dose group, and the combined decoction was superior to the individual decoction. SBG-CCF gavage can reduce the activity of AST, ALT, TC, TG, LDH, and MDA in the serum and liver of ALI rats, while increasing the levels of SOD and GSH. Network pharmacological analysis identified 39 active components, mainly flavonoids and alkaloids. Enrichment analysis suggested that SBG-CCF may treat ALI through the regulation of tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), interleukin-17 (IL-17), apoptosis, and the Toll-like receptor signaling pathways. The key targets in the Disease-Signaling Pathway-Target Network were MAPK8, IKBKB, MAPK10, MAPK3, MAPK1, and AKT1. qRT-PCR results indicated that targets regulating inflammation and lipid metabolism are MAPK8, MAPK10, MAPK3, and AKT1. CONCLUSION: SBG-CCF separately extracts and combines decoction can alleviate acute alcoholic liver injury, and the effect of combined decoction is more significant than separate decoction, implying that the precipitate produced by the combination of the two is also an active substance. The resistance mechanism of SBG-CCF ALI may be related to the modulation of lipid metabolism, inhibition of lipid peroxidation, and oxidative stress. SBG-CCF has the characteristics of multi-component, multi-pathway, and multi-target resistance to ALI.

Combination of Coptis chinensis polysaccharides and berberine ameliorates ulcerative colitis by regulating gut microbiota and activating AhR/IL-22 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch. polysaccharide (CCP) and berberine (BBR) are the primary active components of Coptis chinensis Franch. BBR is clinically used for the treatment of intestinal infections and gastroenteritis. CCP was also reported to be effective for the treatment of ulcerative colitis (UC). However, whether CCP combined with BBR shows a synergistic effect on the treatment of UC has not been elucidated yet. AIM OF THE STUDY: This study aspired to investigate the therapeutic effect and the possible mechanisms of the combination of CCP with BBR on chronic UC. MATERIALS AND METHODS: By periodic administration of dextran sulfate sodium (DSS) to C57BL/6J mice, chronic UC model mice were induced. CCP (15 mg/kg), BBR (50 mg/kg), and CCP.BBR (a combination of 15 mg/kg CCP and 50 mg/kg BBR) were orally administered to the model mice for 10 days. Changes of body weight, disease activity index, colon length, organ index, histopathological damage, expression of cytokines, and intestinal tight junction proteins were determined to evaluate the therapeutic effects. 16S rDNA sequencing, targeted short-chain fatty acid metabolomics, qPCR, and western blotting were performed to elucidate the potential mechanism. RESULTS: Both CCP and BBR alleviated UC via improving colon pathological damage, inhibiting the inflammatory response, and regulating the expression of intestinal tight junction proteins. The combination of CCP with BBR showed a more substantial therapeutic effect via increasing the relative abundance of short-chain fatty acids (SCFAs) producing bacteria, thereby increasing the contents of SCFAs in vivo and activating AhR/IL-22 pathway. CONCLUSION: The combination of CCP and BBR showed a synergistic effect on the therapy of chronic UC and the mechanism was associated with regulating gut microbiota and activating AhR/IL-22 pathway.

Transcriptome and Metabolome Analysis of Isoquinoline Alkaloid Biosynthesis of Coptis chinensis in Different Years.

Coptis chinensis is a perennial herb of the Ranunculaceae family. The isoquinoline alkaloid is the main active component of C. chinensis, mainly exists in its rhizomes and has high clinical application potential. The in vitro synthesis of isoquinoline alkaloids is difficult because their structures are complex; hence, plants are still the main source of them. In this study, two-year and four-year rhizomes of C. chinensis were selected to investigate the effect of growth years on the accumulation of isoquinoline alkaloids. Two-year and four-year C. chinensis were selected for metabolomics detection and transcriptomic analysis. A total of 413 alkaloids were detected by metabolomics analysis, of which 92 were isoquinoline alkaloids. (S)-reticuline was a significantly different accumulated metabolite of the isoquinoline alkaloids biosynthetic pathway in C. chinensis between the two groups. The results of transcriptome analysis showed that a total of 464 differential genes were identified, 36 of which were associated with the isoquinoline alkaloid biosynthesis pathway of C. chinensis. Among them, 18 genes were correlated with the content of important isoquinoline alkaloids. Overall, this study provided a comprehensive metabolomic and transcriptomic analysis of the rapid growth stage of C. chinensis rhizome from the perspective of growth years. It brought new insights into the biosynthetic pathway of isoquinoline alkaloids and provided information for utilizing biotechnology to improve their contents in C. chinensis.

Chemical Characterization of the Precipitate Found in and Its Effect on Drug Release of the Scutellaria†baicalensis-Coptis†chinensis Extract.

Precipitate generation is a challenging issue during the production of herbal decoction as it affects the stability and bioavailability of active compounds. Here we explored the composition of the natural precipitate formed from and its effect on drug release of Scutellaria baicalensis-Coptis chinensis paired extract (SCPE). Furthermore, the surface morphology of the SCPE precipitate was also investigated. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to chemical component analysis and field emission scanning electron microscope (FE-SEM) was performed to particle observation. Baicalin (BA), berberine (BBR) and starch-arginine-rich polymers were abundant in the SCPE precipitate. FE-SEM micrographs showed spheroidal shaped particles in the SCPE supernatant, while spherical and porous tissue-shaped particles in the SCPE precipitate. In vitro drug release of baicalin and berberine contained in the precipitate may increase as the polymer is removed. The presence of polymer-related interactions were confirmed by the greater increase in solubility of baicalin upon addition of arginine and polymer. This was also supported by the solubility decrease of the BA-BBR complex in polymer solution and the gelation of the BA-BBR complex in arginine solution. Our results provide a scientific basis for elucidating the pharmaceutical properties of the decoction of S. baicalensis-C. chinensis-based herbal medicine.

Coptis chinensis and Berberine Ameliorate Chronic Ulcerative Colitis: An Integrated Microbiome-Metabolomics Study.

Coptis chinensis Franch (RC), has historically been used for the treatment of "Xiao Ke" and "Xia Li" symptoms in China. "Xia Li" is characterized by abdominal pain and diarrhea, which are similar to the clinical symptoms of ulcerative colitis (UC). For the first time, this study aims to compare the anti-colitis effects of berberine (BBR) and total RC alkaloids (TRCA) and investigate the underlying metabolites and gut microbiota biomarkers. Metabolomics results showed that several colitis-related biomarkers, including lysophosphatidyl ethanolamine, lysophosphatidylcholine, scopolamine-methyl-bromide, N1-methyl-2-pyridone-5-carboxamide, 4-hydroxyretinoic acid, and malic acid, were significantly improved in model mice after BBR and TRCA treatments. High-dose BBR and TRCA treatments reversed the mouse colon shortening caused by dextran sodium sulfate (DSS), alleviated bowel wall swelling, and reduced inflammatory cell infiltration. BBR and TRCA restored the damaged mucosa integrity in colitis mice by upregulating claudin 1 and occludin, preventing colon epithelium apoptosis by inhibiting the cleavage of caspase 3. Additionally, BBR and TRCA significantly decreased the richness of the pathogenic bacteria Bacteroides acidifaciens but increased the abundance of the probiotic Lactobacillus spp. Notably, TRCA exhibited superior anti-colitis effects to those of BBR. Thus, this agent warrants further study and application in the treatment of inflammatory bowel disease in the clinic.

Coptisine, the Characteristic Constituent from Coptis chinensis, Exhibits Significant Therapeutic Potential in Treating Cancers, Metabolic and Inflammatory Diseases.

Naturally derived alkaloids belong to a class of quite significant organic compounds. Coptisine, a benzyl tetrahydroisoquinoline alkaloid, is one of the major bioactive constituents in Coptis chinensis Franch., which is a famous traditional Chinese medicine. C. chinensis possesses many kinds of functions, including the ability to eliminate heat, expel dampness, purge fire, and remove noxious substances. In Asian countries, C. chinensis is traditionally employed to treat carbuncle and furuncle, diabetes, jaundice, stomach and intestinal disorders, red eyes, toothache, and skin disorders. Up to now, there has been plenty of research of coptisine with respect to its pharmacology. Nevertheless, a comprehensive review of coptisine-associated research is urgently needed. This paper was designed to summarize in detail the progress in the research of the pharmacology, pharmacokinetics, safety, and formulation of coptisine. The related studies included in this paper were retrieved from the following academic databases: The Web of Science, PubMed, Google scholar, Elsevier, and CNKI. The cutoff date was January 2023. Coptisine manifests various pharmacological actions, including anticancer, antimetabolic disease, anti-inflammatory disease, and antigastrointestinal disease effects, among others. Based on its pharmacokinetics, the primary metabolic site of coptisine is the liver. Coptisine is poorly absorbed in the gastrointestinal system, and most of it is expelled in the form of its prototype through feces. Regarding safety, coptisine displayed potential hepatotoxicity. Some novel formulations, including the [Formula: see text]-cyclodextrin-based inclusion complex and nanocarriers, could effectively enhance the bioavailability of coptisine. The traditional use of C. chinensis is closely connected with the pharmacological actions of coptisine. Although there are some disadvantages, including poor solubility, low bioavailability, and possible hepatotoxicity, coptisine is still a prospective naturally derived drug candidate, especially in the treatment of tumors as well as metabolic and inflammatory diseases. Further investigation of coptisine is necessary to facilitate the application of coptisine-based drugs in clinical practice.

[Discovery, isolation and structural identification of alkaloid glycosides in six traditional Chinese medicine such as Coptis chinensis].

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.

Coptis chinensis-Induced Changes in Metabolomics and Gut Microbiota in Rats.

Rhizoma coptidis (CR) is traditionally used for treating gastrointestinal diseases. Wine-processed CR (wCR), zingiber-processed CR (zCR), and evodia-processed CR (eCR) are its major processed products. However, the related study of their specific mechanisms is very limited, and they need to be further clarified. The aim of this study is to compare the intervening mechanism of wCR/zCR/eCR on rats via faecal metabolomics and 16S rDNA gene sequencing analysis. First, faecal samples were collected from the control and CR/wCR/zCR/eCR groups. Then, a metabolomics analysis was performed using UHPLC-Q/TOF-MS to obtain the metabolic profile and significantly altered metabolites. The 16S rDNA gene sequencing analysis was carried out to analyze the composition of gut microbiota and screen out the significantly altered microbiota at the genus level. Finally, a pathway enrichment analysis of the significantly altered metabolites via the KEGG database and a functional prediction of relevant gut microbes based on PICRUSt2 software were performed in combination. Together with the correlation analysis between metabolites and gut microbiota, the potential intervening mechanism of wCR/zCR/eCR was explored. The results suggested that wCR played a good role in maintaining immune homeostasis, promoting glycolysis, and reducing cholesterol; zCR had a better effect on protecting the integrity of the intestinal mucus barrier, preventing gastric ulcers, and reducing body cholesterol; eCR was good at protecting the integrity of the intestinal mucus barrier and promoting glycolysis. This study scientifically elucidated the intervening mechanism of wCR/zCR/eCR from the perspective of faecal metabolites and gut microbiota, providing a new insight into the processing mechanism research of Chinese herbs.

Effects of a compound Trichoderma agent on Coptis chinensis growth, nutrients, enzyme activity, and microbial community of rhizosphere soil.

Background: Root rot diseases are prevalent in many Coptis chinensis Franch. production areas, perhaps partially due to the overuse of synthetic fertilizers. Synthetic fertilizers can also lead to soil degradation. Trichoderma is widely used in biofertilizers and biopesticides. This study applied a combination of four Trichoderma species (compound Trichoderma agent, CTA) to C. chinensis and evaluated its effects on growth, as well as rhizosphere soil nutrients, enzyme activities, and microbial community structure. The purpose of this study was to estimate the potential of using CTA as a biofertilizer for C. chinensis, and determine if it could, at least partially, replace synthetic fertilizers to control root rot disease and maintain soil fertility. Method: CTA, compound fertilizer and sterile water were applied to C. chinensis plants. After 60 days, the soluble sugar, soluble protein, chlorophyll of leaves, and individual weight of each plant were measured. The rhizosphere soil nutrient content, enzymatic activity, and the microbial community were also determined. The results were analyzed to evaluate the effect of CTA on C. chinensis growth and soil fertility. Results: CTA increased the soluble protein, chlorophyll, and individual weight of C. chinensis plants while compound fertilizer decreased chlorophyll. CTA increased the activities of urease and catalase in rhizosphere soil, whereas the compound fertilizer decreased urease, catalase, and alkaline phosphatase activities. CTA elevated soil pH, while compound fertilizer reduced it. CTA had no significant effects on soil nutrients and organic matter. CTA decreased the fungal number and alpha-diversity of fungi and bacteria, and both the fungal and bacterial communities were significantly different from the other two. CTA increased B/F value, which improved the rhizosphere microbial community. Both CTA and the compound fertilizer significantly altered the soil microbial community. The relative abundance of Ascomycota was higher and Basidiomycota was lower after CTA treatment than after the other two treatments, indicating that the soil treated with CTA was healthier than that of the other two treatments. CTA decreased harmful Ilyonectria mors-panacis and Corynebacterium sp. And increased beneficial Ralstonia picketti. Trichoderma spp. could exist in C. chinensis rhizosphere soil for a long time. The functional prediction results demonstrated that CTA reduced some rhizosphere phytopathogenic fungi. Correlation analysis showed that CTA elevated rhizosphere pH and enzyme activities. In summary, synthetic fertilizers damaged soil fertility, and the overuse of them might be responsible for root rot disease, while CTA could promote C. chinensis growth, improve soil and decrease the incidence and severity of C. chinensis root rot disease. Therefore, as a biofertilizer, CTA can, at least partially, replace synthetic fertilizers in C. chinensis production. Combining it with organic fertilizer will increase the potential of Trichoderma.