Molecular insights into chronic atrophic gastritis treatment: Coptis chinensis Franch studied via network pharmacology, molecular dynamics simulation and experimental analysis.

Chronic atrophic gastritis (CAG), characterized by inflammation and erosion of the gastric lining, is a prevalent digestive disorder and considered a precursor to gastric cancer (GC). Coptis chinensis France (CCF) is renowned for its potent heat-clearing, detoxification, and anti-inflammatory properties. Zuojin Pill (ZJP), a classic Chinese medicine primarily composed of CCF, has demonstrated effectiveness in CAG treatment. This study aims to elucidate the potential mechanism of CCF treatment for CAG through a multifaceted approach encompassing network pharmacology, molecular docking, molecular dynamics simulation and experimental verification. The study identified three major active compounds of CCF and elucidated key pathways, such as TNF signaling, PI3K-Akt signaling and p53 signaling. Molecular docking revealed interactions between these active compounds and pivotal targets like PTGS2, TNF, MTOR, and TP53. Additionally, molecular dynamics simulation validated berberine as the primary active compound of CCF, which was further confirmed through experimental verification. This study not only identified berberine as the primary active compound of CCF but also provided valuable insights into the molecular mechanisms underlying CCF's efficacy in treating CAG. Furthermore, it offers a reference for refining therapeutic strategies for CAG management.

Benzyl-isoquinoline alkaloids rich extract of Coptis teeta Wall., exhibit potential efficacy in calcium-oxalate and uric-acid linked metabolic disorders.

Coptis teeta Wall., an endangered but valuable medicinal species having various folklore uses in Indian and Chinese Traditional system of medicine. Its distribution is restricted to India, China and Tibet. In India, C. teeta is traditionally used in joint disorders, urinary infections and inflammatory diseases, however the scientific validation is missing. Thus, the present study aims to validate the anti-lithiatic and anti-gout activity of C. teeta rhizome extract (CTME) through in-vitro biological assays. The metabolic fingerprinting of CTME through reverse phase-high performance liquid chromatography-photodiode array (RP-HPLC-PDA) showed the presence of five benzyl-isoquinoline alkaloids, namely berberine (2.59%), coptisine (0.746%) jatrorrhizine (0.133%), palmatine (0.03%) and tetrahydropalmatine (0.003%). The anti-gout potency analysed via in-vitro xanthine oxidase (XOD) inhibition assay, followed by HPTLC (High performance thin layer chromatography) mediated bio-autographic inhibition of XOD signifies that CTME exhibit strong inhibition of XOD (IC50: 3.014 µg/ml), insignificantly different (p > 0.05) from allopurinol (IC50: 2.47 µg/ml). The XOD bioautographic assay advocates that the efficacy is primarily due to berberine and coptisine alkaloids. The CTME has significant anti-lithiatic activity, and thereby limiting the progression of crystal nidus formation, mediated via inhibition of calcium oxalate crystals nucleation and aggregation. Additionally, the extract also exhibits potential effect on inhibition of oxidative stress associated inflammation, which plays crucial role in alleviating urolithiasis and gouty conditions. Validating the traditional claims of C. teeta will not only confirm its medicinal benefits for targeted pathological conditions but also enhance its industrial demand.

Effects of three Huanglian-derived polysaccharides on the gut microbiome and fecal metabolome of high-fat diet/streptozocin-induced type 2 diabetes mice.

Plant-derived polysaccharides are important components for biological functions. The objective of this study is to study the mechanisms by which polysaccharides from three Huanglian (Rhizome Coptidis, HL) of Coptis chinensis, C. deltoidea, and Coptis teeta affect type 2 diabetes mellitus (T2DM) by analyzing the gut microbiome and their metabolites. A long-term high-fat diet (HFD) combined with streptozocin (STZ) induction was used to construct the T2DM mice model. The histopathology of liver, pancreas, and colon, biochemical indexes related to mice were determined to assess the ameliorative effects of these three HL polysaccharides (HLPs) on T2DM. The results indicated that oral HLPs improved hyperglycemia, insulin resistance, blood lipid levels, and ß-cell function. Further, HLPs elevated the growth of advantageous beneficial bacteria within the gut microbiota and raised the concentrations of short-chain fatty acids (SCFAs), particularly butyric acid. Metabolic analyses showed that HLPs ameliorated the effects of T2DM on microbial-derived metabolites and related metabolic pathways, especially the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. In the combined analysis, many associations of T2DM-related biochemical indicators with gut microbes and their metabolites were extracted, which suggested the important role of gut microbiome and fecal metabolome in the amelioration of type 2 diabetes mellitus by HLPs.

Multidirectional Intervention of Chinese Herbal Medicine in the Prevention and Treatment of Atherosclerosis: From Endothelial Protection to Immunomodulation.

Atherosclerosis is a significant risk factor for developing cardiovascular disease and a leading cause of death worldwide. The occurrence of atherosclerosis is closely related to factors such as endothelial injury, lipid deposition, immunity, and inflammation. Conventional statins, currently used in atherosclerosis treatment, have numerous adverse side effects that limit their clinical utility, prompting the urgent need to identify safer and more effective therapeutic alternatives. Growing evidence indicates the significant potential of Chinese herbs in atherosclerosis treatment. Herbal monomer components, such as natural flavonoid compounds extracted from herbs like Coptis chinensis and Panax notoginseng, have been utilized for their lipid-lowering and inflammation-inhibiting effects in atherosclerosis treatment. These herbs can be used as single components in treating diseases and with other Chinese medicines to form herbal combinations. This approach targets the disease mechanism in multiple ways, enhancing the therapeutic effects. Thus, this review examines the roles of Chinese herbal medicine monomers and Chinese herbal compounds in inhibiting atherosclerosis, including regulating lipids, improving endothelial function, reducing oxidative stress, regulating inflammation and the immune response, and apoptosis. By highlighting these roles, our study offers new perspectives on atherosclerosis treatment with Chinese herbs and is anticipated to contribute to advancements in related research fields.

Discovery of Nine Dipeptidyl Peptidase-4 Inhibitors from Coptis chinensis Using Virtual Screening, Bioactivity Evaluation, and Binding Studies.

The objective of this study was to identify multiple alkaloids in Coptis chinensis that demonstrate inhibitory activity against DPP-4 and systematically evaluate their activity and binding characteristics. A combined strategy that included molecular docking, a DPP-4 inhibition assay, surface plasmon resonance (SPR), and a molecular dynamics simulation technique was employed. The results showed that nine alkaloids in Coptis chinensis directly inhibited DPP-4, with IC50 values of 3.44-53.73 µM. SPR-based binding studies revealed that these alkaloids display rapid binding and dissociation characteristics when interacting with DPP-4, with KD values ranging from 8.11 to 29.97 µM. A molecular dynamics analysis revealed that equilibrium was rapidly reached by nine DPP-4-ligand systems with minimal fluctuations, while binding free energy calculations showed that the ∆Gbind values for the nine test compounds ranged from -31.84 to -16.06 kcal/mol. The most important forces for the binding of these alkaloids with DPP-4 are electrostatic interactions and van der Waals forces. Various important amino acid residues, such as Arg125, His126, Phe357, Arg358, and Tyr547, were involved in the inhibition of DPP-4 by the compounds, revealing a mechanistic basis for the further optimization of these alkaloids as DPP-4 inhibitors. This study confirmed nine alkaloids as direct inhibitors of DPP-4 and characterized their binding features, thereby providing a basis for further research and development on novel DPP-4 inhibitors.

Antipathogenic Activities of Volatile Organic Compounds Produced by Bacillus velezensis LT1 against Sclerotium rolfsii LC1, the Pathogen of Southern Blight in Coptis chinensis.

This study explores the antipathogenic properties of volatile organic compounds (VOCs) produced by Bacillus velezensis LT1, isolated from the rhizosphere soil of Coptis chinensis. The impact of these VOCs on the mycelial growth of Sclerotium rolfsii LC1, the causative agent of southern blight in C. chinensis, was evaluated using a double Petri-dish assay. The biocontrol efficacy of these VOCs was further assessed through leaf inoculation and pot experiments. Antifungal VOCs were collected using headspace solid-phase microextraction (SPME), and their components were identified via gas chromatography-mass spectrometry (GC-MS). The results revealed that the VOCs significantly inhibited the mycelial growth and sclerotia germination of S. rolfsii LC1 and disrupted the morphological integrity of fungal mycelia. Under the influence of these VOCs, genes associated with chitin synthesis were upregulated, while those related to cell wall degrading enzymes were downregulated. Notably, 2-dodecanone and 2-undecanone exhibited inhibition rates of 81.67% and 80.08%, respectively. This research provides a novel approach for the prevention and management of southern blight in C. chinensis, highlighting the potential of microbial VOCs in biocontrol strategies.

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.

Compound-compound interaction analysis of baicalin and berberine derivatives in aqueous solution.

Baicalin and berberine are biologically active constituents of the crude drugs Scutellaria root and Coptis rhizome/Phellodendron bark, respectively. Baicalin and berberine are reported to combine together as a 1:1 complex that forms yellow precipitates by electrostatic interaction in decoctions of Kampo formulae containing these crude drugs. However, the structural basis and mechanism for the precipitate formation of this compound-compound interaction in aqueous solution remains unclarified. Herein, we searched for berberine derivatives in the Coptis rhizome that interact with baicalin and identified the chemical structures involved in the precipitation formation. Precipitation assays showed that baicalin formed precipitates with berberine and coptisine but not with palmatine and epiberberine. Thus, the 2,3-methylenedioxy structure may be crucial to the formation of the precipitates, and electrostatic interaction is necessary but is not sufficient. In this multicomponent system experiment, palmatine formed a dissociable complex with baicalin and may competitively inhibit the formation of berberine and coptisine precipitation with baicalin. Therefore, the precipitation formed by berberine and baicalin was considered to be caused by the aggregation of the berberine-baicalin complex, and the 2,3-methylenedioxy structure is likely crucial to the aggregation of the complex.

Biomarkers and coptis chinensis activity for rituximab-resistant diffuse large B-cell lymphoma: Combination of bioinformatics analysis, network pharmacology and molecular docking.

BACKGROUND: Rituximab resistance is one of the great challenges in the treatment of diffuse large B-cell lymphoma (DLBCL), but relevant biomarkers and signalling pathways remain to be identified. Coptis chinensis and its active ingredients have antitumour effects; thus, the potential bioactive compounds and mechanisms through which Coptis chinensis acts against rituximab-resistant DLBCL are worth exploring. OBJECTIVE: To elucidate the core genes involved in rituximab-resistant DLBCL and the potential therapeutic targets of candidate monomers of Coptis chinensis. METHODS: Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Similarity Ensemble Approach and Swiss Target Prediction, the main ingredients and pharmacological targets of Coptis chinensis were identified through database searches. Through the overlap between the pharmacological targets of Coptis chinensis and the core targets of rituximab-resistant DLBCL, we identified the targets of Coptis chinensis against rituximab-resistant DLBCL and constructed an active compound-target interaction network. The targets and their corresponding active ingredients of Coptis chinensis against rituximab-resistant DLBCL were molecularly docked. RESULTS: Berberine, quercetin, epiberberine and palmatine, the active components of Coptis chinensis, have great potential for improving rituximab-resistant DLBCL via PIK3CG. CONCLUSION: This study revealed biomarkers and Coptis chinensis-associated molecular functions for rituximab-resistant DLBCL.

Enhancing ß-cell function and identity in type 2 diabetes: The protective role of Coptis deltoidea C. Y. Cheng et Hsiao via glucose metabolism modulation and AMPK signaling activation.

BACKGROUND: Abnormalities in glucose metabolism may be the underlying cause of ß-cell dysfunction and identity impairment resulting from high glucose exposure. In China, Coptis deltoidea C. Y. Cheng et Hsiao (YL) has demonstrated remarkable hypoglycemic effects. HYPOTHESIS/PURPOSE: To investigate the hypoglycemic effect of YL and determine the mechanism of YL in treating diabetes. METHODS: A type 2 diabetes mouse model was used to investigate the pharmacodynamics of YL. YL was administrated once daily for 8 weeks. The hypoglycemic effect of YL was assessed by fasting blood glucose, an oral glucose tolerance test, insulin levels, and other indexes. The underlying mechanism of YL was examined by targeting glucose metabolomics, western blotting, and qRT-PCR. Subsequently, the binding capacity between predicted AMP-activated protein kinase (AMPK) and important components of YL (Cop, Ber, and Epi) were validated by molecular docking and surface plasmon resonance. Then, in AMPK knockdown MIN6 cells, the mechanisms of Cop, Ber, and Epi were inversely confirmed through evaluations encompassing glucose-stimulated insulin secretion, markers indicative of ß-cell identity, and the examination of glycolytic genes and products. RESULTS: YL (0.9 g/kg) treatment exerted notable hypoglycemic effects and protected the structural integrity and identity of pancreatic ß-cells. Metabolomic analysis revealed that YL inhibited the hyperactivated glycolysis pathway in diabetic mice, thereby regulating the products of the tricarboxylic acid cycle. KEGG enrichment revealed the intimate relationship of this process with the AMPK signaling pathway. Cop, Ber, and Epi in YL displayed high binding affinities for AMPK protein. These compounds played a pivotal role in preserving the identity of pancreatic ß-cells and amplifying insulin secretion. The mechanism underlying this process involved inhibition of glucose uptake, lowering intracellular lactate levels, and elevating acetyl coenzyme A and ATP levels through AMPK signaling. The use of a glycolytic inhibitor corroborated that attenuation of glycolysis restored ß-cell identity and function. CONCLUSION: YL demonstrates significant hypoglycemic efficacy. We elucidated the potential mechanisms underlying the protective effects of YL and its active constituents on ß-cell function and identity by observing glucose metabolism processes in pancreatic tissue and cells. In this intricate process, AMPK plays a pivotal regulatory role.

Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota.

BACKGROUND: Berberine is the main bioactive constituent of Coptis chinensis, a quaternary ammonium alkaloid. While berberine's cardiovascular benefits are well-documented, its impact on thrombosis remains not fully understood. PURPOSE: This study investigates the potential of intestinal microbiota as a novel target for preventing thrombosis, with a focus on berberine, a natural compound known for its effectiveness in managing cardiovascular conditions. METHODS: Intraperitoneal injection of carrageenan induces the secretion of chemical mediators such as histamine and serotonin from mast cells to promote thrombosis. This model can directly and visually observe the progression of thrombosis in a time-dependent manner. Thrombosis was induced by intravenous injection of 1 % carrageenan solution (20 mg/kg) to all mice except the vehicle control group. Quantitative analysis of gut microbiota metabolites through LC/MS. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of gut microbiota on thrombosis were explored by fecal microbiota transplantation. RESULTS: Our research shows that berberine inhibits thrombosis by altering intestinal microbiota composition and related metabolites. Notably, berberine curtails the biosynthesis of phenylacetylglycine, a thrombosis-promoting coproduct of the host-intestinal microbiota, by promoting phenylacetic acid degradation. This research underscores the significance of phenylacetylglycine as a thrombosis-promoting risk factor, as evidenced by the ability of intraperitoneal phenylacetylglycine injection to reverse berberine's efficacy. Fecal microbiota transplantation experiment confirms the crucial role of intestinal microbiota in thrombus formation. CONCLUSION: Initiating our investigation from the perspective of the gut microbiota, we have, for the first time, unveiled that berberine inhibits thrombus formation by promoting the degradation of phenylacetic acid, consequently suppressing the biosynthesis of PAG. This discovery further substantiates the intricate interplay between the gut microbiota and thrombosis. Our study advances the understanding that intestinal microbiota plays a crucial role in thrombosis development and highlights berberine-mediated intestinal microbiota modulation as a promising therapeutic approach for thrombosis prevention.

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.

[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.

Identification of the therapeutic effect and molecular mechanism of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) theory believes that clearing heat and promoting dampness is the main treatment method for chronic gastritis. Coptis chinensis Franch. has the effects of clearing heat, detoxifying, and anti-inflammatory; Magnolia officinalis var. biloba can be used to treat abdominal pain, cough, and asthma. Coptis chinensis Franch. and Magnolia officinalis var. biloba can regulate the balance of intestinal microbiota and inhibit inflammatory reactions. AIM: This study will verify the therapeutic effect of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis, and explore its mechanism through transcriptome sequencing. METHODS: Firstly, a rat chronic gastritis model was established, and the anal temperature and body weight changes of the rats before and after modeling were observed. Next, H&E staining, TUNEL assay and ELISA assay were performed on rat gastric mucosal tissues. Subsequently, the key fractions of Coptis chinensis Franch. and Magnolia officinalis var. biloba were obtained by high performance liquid chromatography (HPLC), and a GES-1 cell inflammation model was constructed to select the optimal monomer. Finally, the mechanism of action of Coptis chinensis Franch. and Magnolia officinalis var. biloba was explored through RNA seq. RESULTS: Compared with the control group, the rats in the administered group were in better condition, with higher anal temperature, reduced inflammatory response in gastric mucosal tissue and reduced apoptosis. The optimal fraction Coptisine was subsequently determined by HPLC and GES-1 cell model. RNA-seq analysis revealed that DEG was significantly enriched in ribosomes, NF-κB signaling pathway, etc. The key genes TPT1 and RPL37 were subsequently obtained. CONCLUSIONS: This study verified the therapeutic effects of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis by in vivo and in vitro experiments in rats, identified Coptisine as the optimal component, and obtained two potential target genes.

Ameliorative effects of the Coptis inflorescence extract against lung injury in diabetic mice by regulating AMPK/NEU1 signaling.

BACKGROUND: In diabetic patients, complications are the leading cause of death and disability, while diabetic lung damage has received little research. The Coptis inflorescence extract (CE) has hypoglycemic properties, but the mechanism of its protective role on diabetic lung injury is understood. PURPOSE: This study aims to explore the protective actions and molecular mechanism of CE and its active ingredients in diabetic lung disease. METHOD: Twenty-nine metabolites were identified in the metabolomic profile of CE using HPLC-ESI/MS, and high-content substances of berberine (BBR) and linarin (LIN) were isolated from CE using column chromatography. The potential targets and molecular mechanisms of CE against diabetic lung damage were systematically investigated by network pharmacology and in vitro experimental validation. RESULTS: CE significantly improved lung function and pathology. CE (360 mg/kg) or metformin treatment significantly improved lipid metabolism disorders, including decreased HDL-C and elevated serum TG, TC, and LDL-C levels. Furthermore, CE's chemical composition was determined using the HPLC-QTOF-MS method. CE identified five compounds as candidate active compounds (Berberine, Linarin, Palmatine, Worenine, and Coptisine). Network pharmacology analysis predicted CE contained five active compounds and target proteins, that AMPK, TGFß1, and Smad might be the key targets in treating diabetic lung injury. Then we investigated the therapeutic effect of bioactive compounds of CE on diabetic lung damage through in vivo and in vitro experiments. Intragastric administration with BBR (50 mg/kg) or LIN (20 mg/kg) suppressed weight loss, hyperglycemia, and dyslipidemia, significantly alleviating lung inflammation in diabetic mice. Further mechanism research revealed that LIN or BBR inhibited alveolar epithelial-mesenchymal transition induced by high glucose by regulating AMPK/NEU-mediated signaling pathway. CONCLUSION: In conclusion, the administration of CE can effectively alleviate diabetic lung damage, providing a scientific basis for lowering blood sugar to moisturize lung function. BBR and LIN, the main components of CE, can effectively alleviate diabetic lung damage by regulating AMPK/NEU1 Signaling and inhibiting the TGF-ß1 level, which may be a critical mechanism of its effects.

The colonic metabolism differences of main alkaloids in normal and colitis mice treated with Coptis chinensis Franch. and Sophora flavescens Ait. herbal pair using liquid chromatography-high resolution mass spectrometry method combined with chemometrics.

Coptis chinensis Franch. and Sophora flavescens Ait. is a herbal pair frequently used in treating ulcerative colitis. However, the bio-disposition profile of the major components in the inflamed gut remains unclear, which is essential to understand the pharmacological material basis of this herb pair. Here we established an integral quantitative and chemometric method to deduce the colonic metabolism differences of this herbal pair in normal and colitis mice. With this LC-MS method, a total of 41 components have been found in the Coptis chinensis Franch. and Sophora flavescens Ait. extract, and 28 metabolites were found in the colon after oral administration. Alkaloid and its phase I metabolites were the main components in the colon of normal and colitis mice. The results of principal component analysis at 6 h after oral administration showed significant colonic metabolism differences between normal and colitis mice. Heamap results showed that colitis induced significant changes in the colonic bio-disposition of this herbal pair extract. In particular, in the context of colitis, the phase I metabolism of berberine, coptisine, jatrorrhizine, palmatine,and epiberberine has been inhibited. These results may provide a basis for understanding the pharmacological material basis of Coptis chinensis Franch. and Sophora flavescens Ait. in treating ulcerative colitis.

Study on herb-herb interaction between active components of Plantago asiatica L. seed and Coptis chinensis Franch. rhizoma based on transporters using UHPLC-MS/MS.

The combined efficacy in lowering serum lipid levels and increasing kidney protection of Plantago asiatica L. seed (Plantago) and Coptis chinensis Franch. rhizoma (Coptis) is far better than the effects of either herb alone. This finding suggests that there must be some degree of herb-herb interactions (HHI) affect potency. Here, we chose geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA) as active components in Plantago, and berberine (BBR) as the active component in Coptis, and, using transporter gene-transfected Madin-Darby canine kidney (MDCK) cells in combination with specific substrates and inhibitors, investigated Plantago- Coptis HHIs. We also established a UPLC-MS/MS analytical method to determine substrate content. Results showed that PLA in Plantago was a substrate of rOCT1/2 and rMATE1, and had inhibitory effects on rOCT2 and rMATE1. We also found that ACT is a substrate of rMATE1, but GPA was not a substrate of any transporter that we investigated. When BBR was used as the substrate, the inhibition rate of 10 µM PLA was 53.6% on rOCT2 and 31.5% on rMATE1. The inhibition rates of 30 µM ACT and 30 µM GPA on rMATE1 were 47.0% and 31.0%, respectively. Thus, our findings suggest that GPA, ACT, PLA, and BBR have competitive interactions that are driven by the rOCT2 and rMATE1 transporters. These interactions affect the transport and excretion of compounds and result in efficacy changes after co-administration.

Interventional effect of processing temperature on anti-angiogenesis of Coptis chinensis and screening of active components by UPLC-MS/MS on quail chick chorioallantoic membrane model.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch. (CC), as a commonly used heat-clearing and toxin-resolving traditional Chinese herbal medicine, has gained increased attention for its anti-tumor activity. However, little is known about the anti-tumor angiogenesis effect of CC and its possible bioactive components. Also, it has been shown that temperature affects the quality of CC, albeit whether and how it affects the anti-angiogenic activity of CC is currently unknown. AIM OF THE STUDY: To determine the processing temperatures (40, 60, 80, 120, 140, 150, 160 and 200 °C) at which CC has the strongest anti-angiogenic effect and speculate the possible bioactive components. MATERIALS AND METHODS: The q-CAM model was constructed to explore the anti-angiogenesis agents of CC. The angiogenesis inhibition effects of CC samples at different processing temperatures and its seven alkaloids were determined based on morphological observation and vascular area proportion analysis. UPLC-MS/MS was employed to screen the potent active components of CC on anti-angiogenesis. RESULTS: All the intervention by CC at different processing temperatures and its seven alkaloids could inhibit angiogenesis on q-CAM vessels, as evidenced by a poor vasular development in morphological observation and a low vascular area proportion in vascular quantitative analysis, most evident in CC processed at 40 °C and palmatine. LC-MS revealed that palmatine displayed strongest inhibitory effect on q-CAM vessels with a high absorption due to its stable structure. And the maternal nucleus transformation phenomenon of CC alkaloids was found in the quail embryo metabolism. CONCLUSIONS: The q-CAM models in conjunction with the UPLC-MS/MS technique could be a useful tool for assessing tumor angiogenesis and screening tumor-targeted medicines. Processing temperature can affect the anti-angiogenesis effect of CC because of its function on the content of alkaloids, and palmatine can be considered as a prospective anti-angiogenic drug.

Integrated network pharmacology and DSS-induced colitis model to determine the anti-colitis effect of Rheum palmatum L. and Coptis chinensis Franch in granules.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum L. (RP) and Coptis chinensis Franch. (CC), frequently used as herbal pair (HP) in clinical practicing of traditional Chinese medicine, exerted predominate efficacies in colitis treatment. However, the mechanism of their synergism lacks scientific explanation. AIM OF THE STUDY: By integrating network pharmacology and DSS-induced colitis model, the anti-colitis effects and synergistic molecular mechanisms of RP-CC combination was determined. MATERIALS AND METHODS: In vivo study, mice were divided into control, model, RP, CC and RP-CC (low, middle, high) groups, 2.5% DSS was administrated to induce colitis for consecutive 7 days, subsequently, the therapeutic effects were evaluated from body weight changes, disease activity index (DAI), and pathological conditions. After determining the shared and exclusive targets of RP and CC, respectively by network pharmacology, CETSA, WB, and qPCR were utilized to verify the action modes of RP and CC on specific targets. RESULTS: Compared to RP or CC used alone, RP-CC combination can significantly protect colon tissues from inflammatory damage in a dose-dependent manner via remarkably alleviating DAI and colon shortening. Network pharmacological analysis suggested that AKT1 would be the core target for RP-CC synergism since these two herbs could simultaneously but non-competitively bind to AKT1 at different sits. Furthermore, RP and CC could also influencing HIF and MAPK pathways, respectively, these additional actions attribute to more optimizing effectiveness towards colitis. CONCLUSION: In contrast to the mild therapeutic effects of RP or CC individually, RP-CC herb pair could exert strong and synergistic effects in treatment of colitis via non-competitive binding to AKT1 simultaneously, as well as exclusively influencing MAPK and HIF pathways. Our study not only provides the evidence for understanding the combined effect of RP and CC, but also brings up a new strategy and suggestive thoughts for the rationality of HP-based TCM formula.