Coptidis Rhizoma Research Articles

Heavy metal ions in herbal medicine sometimes exceed the standard limit, inducing severe and harmful problems in human health. Exploring new nanomaterials to chelate heavy metal ions and reduce their concentration in herbal decoctions could be a solution route. In this study, the nanoadsorbent poly(2-(hydroxymethyl)acrylic acid (PHMAA) was prepared via free radical polymerization and the hydrolysis method. PHMAA showed excellent dispersion in aqueous solution and self-assembled into spherical aggregates with a negative surface charge. After freeze-drying, PHMAA was a white solid powder with a loose porous structure. PHMAA presented no significant influence on the cell viability and weight of normal BALB/c mice. PHMAA showed good removal efficiency towards Cd2+ ions in aqueous solution; the removal rate exceeded 80%. In herbal decoctions, PHMAA presented moderate to good removal capacity towards Cd2+ ions; the removal rate was 60%, 83%, and 89% for the Morindae officinalis radix decoction, Ligusticum wallichii decoction, and Coptidis rhizome decoction, separately. When the concentration of Cd2+ ions in the decoction was decreased to 5 μg/mL, PHMAA also presented good removal efficiency. During the removal process, PHMAA played no influence on the active ingredients. To conclude, PHMAA showed good biosafety and removal capacity towards Cd2+ ions, which might be utilized as nanoadsorbents to reduce the concentration of Cd2+ ions in aqueous solution and herbal decoctions.

Co-administration of berberine and evodiamine: Mitigating evodiamine-induced hepatotoxicity and potentiating colitis treatment.

Berberine suppresses colorectal cancer progression by inducing ferroptosis-mediated energy metabolism disorders.

Sleep disorders (SD) affect approximately 25% of the global population. Traditional Chinese Medicine (TCM) formulas have been shown to alleviate SD by modulating endogenous melatonin. This study used data mining, network pharmacology, and meta-analysis to identify key herbal pairs from TCM formulas and the mechanism of action. Literature was retrieved from PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data Information Site, China Science and Technology Journal Database, and SinoMed. R was used for frequency and association rule analysis, SPSS for clustering, and Cytoscape, STRING, Gene Ontology, and KEGG enrichment analyses were utilized to explore targets, protein-protein interactions, and pathways. A meta-analysis using the Metan command was performed to assess the optimal herbal pairs for SD treatment. Data mining identified 77 commonly used herbs, revealing four advantageous herbal pairs: PAEONIAE RADIX ALBA (PRA)-BUPLEURI RADIX (BR), COPTIDIS RHIZOMA (CR)- CINNAMOMI CORTEX (CC), PORIA (PA)-BUPLEURI RADIX (BR), and ZIZIPHI SPINOSAE SEMEN (ZSS)-MARGARITIFERA CONCHA (MC). Network pharmacology showed that (PRA-BR)-SD, (PA-BR)-SD, (CR-CC)-SD, and (ZSS-MC)-SD targeted CACNA1D, GRIN2A, AGT, and ATP1A1 via prion diseases, nicotine addiction, neuroactive ligand-receptor interaction, and cardiac muscle contraction pathways, respectively. Research shows that CACNA1D could regulate Ca²⁷ inward flow, avoid mitochondrial dysfunction in prion diseases, and reduce ROS generation, thus indirectly maintaining MT levels and sleep. GRIN2A as an amygdala hub gene closely related to daily smoking, combining brain transcriptome analysis and tobacco consumption GWAS data. The sleep regulation mechanism of MT relies on the neuroactive ligand-receptor pathway. As a neuroactive ligand, MT triggers sleep-promoting physiological responses by activating the G-protein-coupled receptors MT1 and MT2 and transmitting "night" signals to the relevant neural networks. Insufficient MT secretion or circadian rhythm disruption might lead to abnormal blood pressure rhythms accompanied by sympathetic overactivation, increasing the risk of insomnia and cardiovascular disease. ATP1A1 is a key molecule in the maintenance of electrochemical gradients in cardiac myocytes through the modulation of the Na⁷/K⁷ homeostasis affects myocardial excitability, calcium kinetics, and contractile function. Meta-analysis and network pharmacology suggest that the PA-BR pair might offer superior efficacy by modulating membrane potential and nicotine addiction pathways, targeting GRIN2A, GRIN1, GRIN3A, and GRIN2B to regulate melatonin levels.

Berberine attenuates liver fibrosis via inhibition of Ang-2 through the toll-like receptor 4-mediated signaling pathway.

ObjectiveDahuang (Rhei Radix et Rhizoma)-Huanglian (Coptidis Rhizoma) (DHHL), has been shown to effectively treat obesity caused by dietary irregularities. Nevertheless, the fundamental process driving this phenomenon has yet to be elucidated.MethodsThe chemical constituents of DHHL were analyzed using UPLC-MS/MS. An obesity model was established in rats by high-fat diet (HFD) induction and verified accordingly. Obese rats were administered various doses of DHHL. Detect and record the metabolic indicators of rats in each group. Transcriptomic analysis was used to evaluate the influence of DHHL on gene expression in obese rats. H&E staining and transmission electron microscopy (TEM) was used to observe the morphology of adipocytes. Immunohistochemistry (IHC), fluorescent immunohistochemistry (FIHC), and Western blotting (WB) were performed to detect protein expression levels.ResultsThe chemical constituents of DHHL medicinal materials were identified and analyzed using UPLC-MS/MS. Total ion chromatograms (TIC) were acquired in both positive and negative ion modes. Pie charts were generated to illustrate the abundance distribution and quantitative proportion of different components. HFD feeding induced significant increases in body weight and FBG in rats, elevated serum triglycerides (TG) and free fatty acids (FFA) levels, and promoted hypertrophy and hyperplasia of adipose tissue, while also disrupting glucose metabolism. DHHL treatment significantly improved body weight, FBG, glucose uptake capacity, and insulin sensitivity in obese rats. It also reduced blood lipid levels and lipid accumulation in a dose-dependent manner. Transcriptomic sequencing revealed that the anti-obesity effects of DHHL were closely associated with the upregulation of thermogenesis-related gene expression. KEGG pathway enrichment analysis indicated that DHHL may exert regulatory effects through pathways such as AMPK, PPAR, and PI3K. TEM observations demonstrated that DHHL increased mitochondrial numbers within adipocytes of obese rats. Molecular analyses further showed that DHHL upregulated the expression of thermogenesis-associated proteins—including PPARγ, PRDM16, and UCP1—thereby promoting the browning of white adipose tissue (WAT). Moreover, DHHL enhanced the expression levels of AMPK, SIRT1, and PGC-1α.ConclusionsDHHL effectively ameliorates HFD-induced obesity in rats, and its therapeutic mechanism is closely associated with the activation of the AMPK/SIRT1/PGC-1α signaling pathway, which promotes the browning of WAT.

BackgroundObesity-induced adipose hypoxia activates the hypoxia-inducible factor alpha (HIF-α) axis, where HIF-1α and HIF-2α exhibit functional antagonism: HIF-1α exacerbates insulin resistance (IR) and inflammation, whereas HIF-2α counteracts these effects. This dichotomy suggests dual targeting (inhibiting HIF-1α/activating HIF-2α) could synergistically ameliorate obesity-associated IR. Coptidis Rhizoma and Scutellariae Radix, a classic traditional Chinese medicine (TCM) pair for damp-heat obesity-demonstrate efficacy, but their synergistic components and mechanistic basis remain unclear. Therefore, this study aims to identify active ingredients through the dual targeting strategy and subsequently validate their therapeutic efficacy.MethodsBased on the dual-targeting strategy, potential active ingredients were identified using a specifically designed dual-luciferase reporter system that simultaneously inhibits HIF-1α and activates HIF-2α. The optimal synergistic ratio was determined by applying the Loewe model. In vitro anti-inflammatory efficacy was evaluated in macrophages stimulated with palmitic acid or lipopolysaccharide. In vivo effects were assessed in a high-fat diet-induced obese mouse. Insulin sensitivity was determined by measuring fasting blood glucose levels and performing oral glucose tolerance test and insulin tolerance tests. Tissues were analysed for lipid metabolism and inflammatory markers via immunohistochemistry, quantitative real-time PCR, and enzyme-linked immunosorbent assay.ResultsBerberine (BBR) and wogonin (WOG) were identified from herb pair to inhibit HIF-1α and activate HIF-2α in an optimal synergistic ratio of 3:1. At this ratio, the combination significantly ameliorated the secretion of pro-inflammatory cytokines in vitro. Consistent with the in vitro findings, co-administration of BBR and WOG (3:1) showed lipid-lowering effects comparable to metformin and effectively improved insulin sensitivity in obese mice. Additionally, improved lipid metabolism-related parameters including plasma total cholesterol and free fatty acids, thereby mitigating hepatic lipid accumulation.ConclusionsThe synergistic constituents of Coptidis Rhizoma-Scutellariae Radix, namely BBR and WOG, synergistically alleviate IR associated with obesity by inhibiting HIF-1α and activating HIF-2α, respectively. This study elucidates the mechanistic basis of herbal combination therapy for metabolic disorders and provides a foundation for developing novel synergistic therapeutics against obesity-related IR.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13020-025-01223-w.

Coptidis Rhizome alleviates dexamethasone- and fructose-induced metabolic disorder in rats as an inducer of HO-1 agonist via erythrocyte metabolism.

Joint multi-technology applications for etablishing quality evaluation model of Coptidis Rhizoma.

Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease (IBD). Huanglian Ganjiang decoction (HGD), derived from ancient book Beiji Qianjin Yao Fang, has demonstrated efficacy in treating UC patients traditionally. Previous research established that the compatibility of cold herb Coptidis Rhizoma + Phellodendri Chinensis Cortex (CP) and hot herb Angelicae Sinensis Radix + Zingiberis Rhizoma (AZ) in HGD synergistically improved colitis mice. This study investigated the compatibility mechanisms through which CP and AZ regulated inflammatory balance in colitis mice. The experimental colitis model was established by administering 3% dextran sulphate sodium (DSS) to mice for 7 days, followed by CP, AZ and CPAZ treatment for an additional 7 days. M1/M2 macrophage polarization levels, glucose metabolites levels and pyruvate dehydrogenase kinase 4 (PDK4) expression were analyzed using flow cytometry, Western blot, immunofluorescence and targeted glucose metabolomics. The findings indicated that CP inhibited M1 macrophage polarization, decreased inflammatory metabolites associated with tricarboxylic acid (TCA) cycle, and suppressed PDK4 expression and pyruvate dehydrogenase (PDH) (Ser-293) phosphorylation level. AZ enhanced M2 macrophage polarization, increased lactate axis metabolite lactate levels, and upregulated PDK4 expression and PDH (Ser-293) phosphorylation level. TCA cycle blocker AG-221 and adeno-associated virus (AAV)-PDK4 partially negated CP's inhibition of M1 macrophage polarization. Lactate axis antagonist oxamate and PDK4 inhibitor dichloroacetate (DCA) partially reduced AZ's activation of M2 macrophage polarization. In conclusion, the compatibility of CP and AZ synergistically alleviated colitis in mice through M1/M2 macrophage polarization balance via PDK4-mediated glucose metabolism reprogramming. Specifically, CP reduced M1 macrophage polarization by restoration of TCA cycle via PDK4 inhibition, while AZ increased M2 macrophage polarization through activation of PDK4/lactate axis.

BackgroundCoptidis rhizoma, a botanical drug derived from the dried rhizome of Coptis species (e.g., Coptis chinensis), is characterized by abundant natural sources, significant bioactivity, and high safety. It holds considerable potential for translational applications in metabolic diseases, particularly in ameliorating type 2 diabetes mellitus (T2DM)-related metabolic dysfunction-associated steatohepatitis (MASH). However, mechanistic studies on Coptidis rhizoma remain limited.PurposeThis study aimed to evaluate the therapeutic effects of Coptidis rhizoma on hepatic histological and functional damage, metabolic disorders, and insulin resistance in T2DM-related MASH and investigate its underlying mechanisms.MethodsTwo-day-old male C57BL/6J mice were subcutaneously injected with streptozotocin (200 μg/20 μL per mouse). At 4 weeks of age, the mice were weaned and switched to a high-fat diet until week 9 to induce T2DM-related MASH. Starting from week 5, Coptidis rhizoma decoction was administered via oral gavage for four consecutive weeks to conduct in vivo studies. Additionally, hepatocytes were isolated from the model mice and exposed in vitro to epiberberine, the active metabolite of Coptidis rhizoma, for cellular-level investigations.ResultsCoptidis rhizoma significantly attenuated hepatic inflammatory lesions, reduced the non-alcoholic fatty liver disease activity score, improved liver function, and alleviated glucose and lipid metabolism disorders and insulin resistance in a dose-dependent manner in T2DM-related MASH mice. At the transcriptional level, key components of the interleukin-17 receptor A (IL-17RA)/nuclear factor kappa B (NF-κB) signaling pathway were upregulated in the hepatocytes of T2DM-related MASH mice, and both Coptidis rhizoma and epiberberine downregulated their expressions. Furthermore, Coptidis rhizoma and epiberberine suppressed the secretion of pro-inflammatory cytokines associated with the IL-17RA/NF-κB pathway in hepatocytes.ConclusionCoptidis rhizoma ameliorates pathological phenotypes in T2DM-related MASH by inhibiting the IL-17RA/NF-κB signaling pathway, and its active metabolite epiberberine is involved in mediating these protective effects.

Scutellariae Radix (SR) and Coptidis Rhizoma (CR) are classic drug pairs used in clinical practice for clearing heat and drying dampness, purging fire for removing toxin. By further studying the mechanism of compatibility of SR and CR from the perspective of thermodynamically driven supramolecular phase transition, we could reveal the interaction between its pharmacodynamic components, and provide scientific basis for improving TCM efficacy. The SR-CR and its main components baicalin-berberine (BA-BBR) were taken as the research objects. The morphology of the mechanically mixed samples was characterized by malvern particle size analyzer and scanning electron microscope. UHPLC-Q-Orbitrap HRMS technology was employed to analyze the material basis of each mechanically mixed sample. ITC was used to investigate the effect of temperature on the binding ability between SR and CR. The structural differences of supramolecules in different morphology were explored by molecular dynamics simulation. Finally, in vitro antibacterial models (E. faecium and B. subtilis, S. aureus) were used to evaluate the antibacterial activities of the mechanically mixed samples and non-targeted metabolomics was used to explore the differences in antibacterial mechanisms. The mechanical mixtures formed nanofibers (NFs), while heating induced a transition to nanospheres (NPs). Molecular dynamics simulations revealed that enhanced hydrogen bonding and tighter molecular packing under thermal conditions drove this morphological shift. In vitro antibacterial assays and non-targeted metabolomics showed NPs exhibited superior inhibition against Staphylococcus aureus by disrupting amino acid biosynthesis and metabolism, whereas NFs suppressed Bacillus subtilis via physical entanglement and interfered with energy metabolism. Driven by thermal energy, the existence form of supramolecules changed from NFs to NPs and the morphology of the formed supramolecules was maintained during their interaction with bacteria, further affected the biological activity.

Background & AimsHepatocellular carcinoma (HCC) is a major health concern. T cell exhaustion (Tex), a state of T cell dysfunction characterized by reduced effector function and increased expression of inhibitory receptors. This study aimed to explore the mechanism by which Zuojin capsule (ZJC, Coptidis Rhizoma and Evodiae Fructus) treats HCC and improves Tex.MethodsTo identify HCC-related and Tex-associated targets, two HCC expression microarray datasets were integrated. Targets related to Tex were retrieved from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Active compounds in ZJC were screened. A protein-protein interaction (PPI) network of overlapping targets was constructed using STRING to identify core functional modules. To verify the anti-proliferative effect of ZJC on HCC cells, the CCK-8 assay was performed to detect the viability of Hep3B and HepG2.2.15 cells treated with gradient concentrations of ZJC. Western Blot analysis was conducted to measure the protein expression levels of key molecules. Immunohistochemical (IHC) staining was used to assess the proliferation index of tumor cells, the infiltration of immune cells, and the expression of immune-related markers.ResultsHCC-related genes, Tex targets, and ZJC targets were identified through bioinformatics analysis, 136 overlapping targets were obtained. ZJC inhibited Hep3B/HepG2.2.15 cell proliferation with IC50 values of 310 μg/mL and 530 μg/mL, respectively. The pathway analysis conducted using DAVID revealed that the intersecting targets were mainly enriched in the mTOR signaling pathway and the transcriptional regulation process. H22 xenografts were treated with ZJC or anti-PD-1 to evaluate tumor growth and immune responses. ZJC suppressed HCC cell proliferation and reduced the expression of Ki67. Mechanistically, it downregulated phosphorylated mTOR (p-mTOR), p-eIF4E, and p-p70S6K, and this downregulated state could be reversed by the restoration of mTOR activators. ZJC reduced the expression of cyclin-dependent kinase 1 (CDK1). In HCC tissues, M1 macrophages were reduced, while M2 macrophages and exhausted T cells were accumulated. ZJC treatment inhibited tumor growth and modulated immune infiltration. Additionally, ZJC and anti-PD-1 promoted the expression or aggregation of CD8-positive cells. In addition, the control group showed relatively high positive staining for CD163, whereas ZJC and anti-PD-1 inhibited the expression or aggregation of CD163-positive cells.ConclusionZJC exerts dual anti-tumor effects by inhibiting the mTOR-eIF4E/p70S6K-CDK1 pathway and remodeling the immunosuppressive microenvironment of HCC.

Neuroprotective effect of the herbal pair Coptidis Rhizoma-Cinnamomi Cortex against 6-OHDA-induced Parkinson's disease rats through promotion of autophagy via the PI3K/AKT/mTOR pathway.

Excessive osteoclast activity in bone remodeling can lead to an imbalance between bone resorption and formation, a common occurrence in abnormal bone metabolic diseases. This research investigates the effect of Coptidis rhizoma water extract (CRW) on osteoclastogenesis provoked by RANKL in vitro and bone destruction mediated by ovariectomy (OVX) in vivo. CRW, prepared from dried Coptidis rhizoma (CR), was analyzed for its active compounds—coptisine and berberine—using HPLC analysis. CRW markedly decreased the size and number of TRAP-positive multinucleated cells (TRAP+ MNCs), suppressed F-actin ring formation, and diminished bone resorption in RANKL-treated cultures. In the early phase of differentiation, CRW suppressed the phosphorylation of MAPKs p38, JNK, and ERK, as well as NF-κB p65, Iκ-Bα, and Akt. CRW also down-regulated RANKL-mediated induction of c-Fos and NFATc1 and attenuated the activation of NFATc1- dependent genes, such as OSCAR, ATP6V0D2, ACP5 (TRAP), OC-STAMP, DC-STAMP, CTSK (cathepsin K), CALCR (calcitonin receptor), and MMP-9. In ovariectomized rats, micro-CT and histological analyses showed that CRW alleviated femoral bone destruction. These findings indicate that CRW restrains osteoclast differentiation and function and may have therapeutic potential for disorders driven by excessive osteoclast activity.

Tissue distribution of seven coptidis alkaloids in normal and insomnia rats affected by Cinnamomi cortex (Cinnamomum cassia) using liquid chromatography-tandem mass spectrometry.

This study aimed to investigate the underlying mechanism of action and further identify main active ingredient by which Radix Paeoniae Rubra extracts (RPRE) inhibited the cross-resistance to tetracycline (TET), piperacillin (PIP), and gentamicin (GEN) mediated by Rhizoma Coptidis extracts (RCE) in Staphylococcus aureus (SA). Treatment with mixed solutions of RCE and RPRE resulted in disappearance of TET, PIP, or GEN resistance compared to what was shown with RCE treatment alone. Fifteen relevant resistant genes (smrB, bmr3, nhoA, BTN44_15030, clpL, hisG, norA, fmtA_1, emrB_1, BTN44_07590, paiA, icaR, BTN44_13995, HMPREF0776_1664 and vraG) were significantly downregulated compared to the RCE-induced mutants. RPRE was sequentially fractionated using macroporous resin and silica gel column chromatography, and all resulting eluates exhibited the antibacterial activity against Staphylococcus ATCC 25923. When exposed to RCE combined with either 30% EE or DCM:MeOH(5:1) eluates, no significant cross-resistance to the tested antibiotics was observed in the induced isolates. Similarly, the expression levels of the fifteen resistant genes were markedly reduced. Furthermore, gallic acid (GA) was identified in the two aforementioned eluates using HPLC-MS. After selection with a mixed solution of RCE and GA, the induced strains displayed no cross-resistance to the tested antibiotics, and the expression of the resistant genes was significantly decreased. These results suggest that GA is a key active ingredient in RPRE responsible for suppressing RCE-mediated cross-resistance to TET, PIP, and GEN in SA.

Colorectal cancer, a prevalent digestive system malignancy, is characterized by a high incidence, low early detection rate, limited surgical resection opportunities, and high mortality. Palmatine (PAL), an active ingredient primarily found in Coptidis Rhizoma, exhibits diverse pharmacological effects, including antibacterial, anti-inflammatory, and anti-tumor properties. While PAL has been shown to effectively curb the progression of colorectal cancer, the underlying mechanisms have yet to be fully elucidated. In this study, we demonstrated the inhibitory effect of PAL on colorectal cancer growth via the miR-363-3p/AURKA axis, utilizing an AOM/DSS-induced colorectal cancer model in C57BL/J mice, a subcutaneous tumor xenograft model in nude mice, and in vitro assays using HCT-116 and SW620 cells. PAL upregulates miR-363-3p expression, promotes the interaction between AURKA 3'UTR mRNA and miR-363-3p, impedes AURKA mRNA translation into AURKA protein, thereby inhibiting colorectal cancer cell proliferation and migration, and suppressing the initiation and progression of colorectal cancer. These results expand the understanding of the regulatory mechanisms by which PAL influences colorectal cancer development, and may provide new potential targets for colorectal cancer diagnosis and therapy.

BackgroundBiofilm formation is a key virulence factor in Staphylococcus epidermidis. Rhizoma Coptidis, the medicinal root of Coptis chinensis, has been traditionally used in Chinese medicine for its broad-spectrum antimicrobial properties.ResultsThis study investigated the antibacterial and anti-biofilm effects of Rhizoma Coptidis extract against S. epidermidis ATCC 35984. UPLC-MS/MS analysis revealed the chemical composition of the extract. The extract significantly reduced ATPase and succinate dehydrogenase activities, decreased membrane potential, and disrupted cell wall and membrane integrity. These effects led to increased extracellular alkaline phosphatase activity and leakage of proteins and nucleic acids. Anti-biofilm activity was further confirmed using scanning electron microscopy and confocal laser scanning microscopy. Transcriptomic and metabolomic analyses identified significant changes in 366 genes and 286 metabolites after treatment. Integrated omics analysis suggested that the extract impaired cell membrane and wall integrity, disrupted amino acid and nucleic acid metabolism, inhibited the TCA cycle, reduced nitrate reductase activity, suppressed efflux systems, and hindered biofilm formation.ConclusionsThe study provides new insights into the antibacterial and anti-biofilm mechanisms of Rhizoma Coptidis extract against S. epidermidis, highlighting its potential as a therapeutic agent for combating biofilm-associated infections.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12866-025-04169-z.

Rhizoma Coptidis polysaccharides: extraction, separation, purification, structural characteristics and bioactivities.