RESUMEN
This study used berberine hydrochloride to treat the Asian paddle crab, Charybdis japonica infected with the Gram-negative bacterium Aeromonas hydrophila at concentrations of 0, 100, 200 and 300 mg/L. The effect of berberine hydrochloride on the survival rate and gut microbiota of C. japonica was investigated. Berberine hydrochloride improved the stability of the intestinal flora, with an increase in the abundance of probiotic species and a decrease in the abundance of both pathogenic bacteria after treatment with high concentrations of berberine hydrochloride. Berberine hydrochloride altered peroxidase activity (POD), malondialdehyde (MDA), and lipid peroxidation (LPO) in the intestinal tract compared to the control. Berberine hydrochloride could modulate the energy released from the enzyme activities of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) in the intestinal tract of C. japonica infected with A. hydrophila. Zona occludens 1 (ZO-1), Zinc finger E-box binding homeobox 1 (ZEB1), occludin and signal transducer, and activator of transcription5b (STAT5b) expression were also increased, which improved intestinal barrier function. The results of this study provide new insights into the role of berberine hydrochloride in intestinal immune mechanisms and oxidative stress in crustaceans.
Asunto(s)
Aeromonas hydrophila , Antioxidantes , Berberina , Microbioma Gastrointestinal , Infecciones por Bacterias Gramnegativas , Berberina/farmacología , Aeromonas hydrophila/efectos de los fármacos , Aeromonas hydrophila/genética , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Braquiuros/microbiología , Braquiuros/efectos de los fármacos , Malondialdehído/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/metabolismoAsunto(s)
Acroleína , Berberina , Neoplasias Pulmonares , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/tratamiento farmacológico , Humanos , Berberina/farmacología , Berberina/uso terapéutico , Acroleína/análogos & derivados , Acroleína/farmacología , Animales , Carcinogénesis/efectos de los fármacosRESUMEN
This study compared the capacity of two different models of HIIT [high-(HC) and low-(LC) compression], with or without the use of berberine (BBR), on NOD-like receptor pyrin domain-containing protein-3 (NLRP3), H19, interleukin (IL)-1ß, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance markers. Fifty-four middle-aged men with overweight or obesity and prediabetes [fasting blood glucose (FBG) 110-180 mg/dL] were randomly and equally assigned to the HC, LC, HC + BBR, LC + BBR, BBR, and non-exercising control (CON) groups. The HC (2:1 work-to-rest) and LC (1:1 work-to-rest) home-based training programs included 2-4 sets of 8 exercises at 80%-95% HRmax, twice a week for 8 weeks. Participants in the berberine groups received approximately 1000 mg daily. All exercise interventions led to a significant reduction in hs-CRP, IL-1ß, insulin, FBG, and insulin resistance index (HOMA-IR) versus CON. Notably, there was a significant reduction in FBG and HOMA-IR with the BBR group compared to the baseline. Both NLRP3 and H19 experienced a significant drop only with LC in comparison to the baseline. While both exercise protocols were beneficial overall, LC uniquely exhibited more anti-inflammatory effects, as indicated by reductions in H19 and NLRP3. However, the addition of berberine to the exercise programs did not demonstrate additional benefits.
Asunto(s)
Berberina , Estado Prediabético , Humanos , Masculino , Berberina/farmacología , Berberina/administración & dosificación , Berberina/uso terapéutico , Estado Prediabético/sangre , Persona de Mediana Edad , Resistencia a la Insulina , Entrenamiento de Intervalos de Alta Intensidad/métodos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Adulto , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Suplementos Dietéticos , Interleucina-1beta/sangre , Inflamación/sangreRESUMEN
Bovine mastitis caused by infectious pathogens, mainly Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), constitutes a major destructive challenge for the dairy industry and public health. Berberine chloride (BER) and Cyperus rotundus possess a broad spectrum of anti-inflammatory, antioxidant, antibacterial, and antiproliferative activities; however, their bioavailability is low. This research aimed first to prepare an ethanolic extract of Cyperus rotundus rhizomes (CRE) followed by screening its phytochemical contents, then synthesis of BER and CRE loaded chitosan nanoparticles (NPs) (BER/CH-NPs and CRE/CH-NPs), afterward, the analysis of their loading efficiency in addition to the morphological and physicochemical characterization of the formulated NPs employing Scanning Electron Microscopy (SEM), Zeta Potential (ZP), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) assessments compared to their crude forms to evaluate the enhancement of bioavailability and stability. Isolation of bacterial strains from the milk of mastitic cows, used for induction of mammary gland (MG) inflammation in female albino rats, and a preliminary investigation of the prophylactic oral doses of the prepared NPs against S. aureus-induced mastitis in female rats. The minimal inhibitory concentration (MIC) of BER/CH-NPs and CRE/CH-NPs is 1 mg/kg b.w. BER/CH-NPs and CRE/CH-NPs alone or in combination show significant (P ≤ 0.05) DPPH radical scavenging activity (69.2, 88.5, and 98.2%, respectively) in vitro. Oral administration of BER/CH-NPs and CRE/CH-NPs to mastitis rats significantly (P ≤ 0.05) attenuated TNF-α (22.1, 28.6 pg/ml), IL-6 (33.4, 42.9 pg/ml), IL-18 (21.7, 34.7 pg/ml), IL-4 (432.9, 421.6 pg/ml), and MPO (87.1, 89.3 pg/ml) compared to mastitis group alongside the improvement of MG histopathological findings without any side effect on renal and hepatic functions. Despite promising results with BER and CRE nanoparticles, the study is limited by small-scale trials, a focus on acute administration, and partially explored nanoparticle-biological interactions, with no economic or scalability assessments. Future research should address these limitations by expanding trial scopes, exploring interactions further, extending study durations, and assessing economic and practical scalability. Field trials and regulatory compliance are also necessary to ensure practical application and safety in the dairy industry. In conclusion, the in vitro and in vivo results proved the antioxidant and anti-inflammatory efficacy of BER/CH-NPs and CRE/CH-NPs in low doses with minimal damage to the liver and kidney functions, supposing their promising uses in mastitis treatment.
Asunto(s)
Antiinflamatorios , Antioxidantes , Berberina , Cyperus , Mastitis , Nanopartículas , Extractos Vegetales , Animales , Femenino , Cyperus/química , Ratas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antioxidantes/farmacología , Antioxidantes/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Berberina/farmacología , Berberina/química , Berberina/administración & dosificación , Bovinos , Nanopartículas/química , Mastitis/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Mastitis Bovina/tratamiento farmacológico , Mastitis Bovina/microbiología , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Quitosano/química , Quitosano/farmacologíaRESUMEN
Berberine (BBR), as a natural isoquinoline alkaloid, has demonstrated various pharmacological activities, and is widely applied in the treatment of diseases. The quantitative analysis of BBR is important for pharmacological studies and clinical applications. In this work, utilizing the specific interaction between BBR and triplex DNA, a sensitive and selective fluorescent detecting method was established with DNA-templated silver nanoclusters (DNA-AgNCs). After binding with the triplex structure in the template of DNA-AgNCs, BBR quenched the fluorescence of DNA-AgNCs and formed BBR-triplex complex with yellow-green fluorescence. The ratiometric fluorescence signal showed a linear relationship with BBR concentration in a range from 10 nM to 1000 nM, with a detection limit of 10 nM. Our method exhibited excellent sensitivity and selectivity, and was further applied in BBR detection in real samples.
Asunto(s)
Berberina , ADN , Nanopartículas del Metal , Plata , Espectrometría de Fluorescencia , Berberina/química , Berberina/análisis , Plata/química , Nanopartículas del Metal/química , ADN/química , ADN/análisis , Espectrometría de Fluorescencia/métodos , Fluorescencia , Límite de Detección , HumanosRESUMEN
The rising incidence of colorectal cancer (CRC) and gastric cancer (GC) worldwide, coupled with the limited effectiveness of current chemotherapeutic agents, has prioritized the search for new therapeutic options. Natural substances, which often exhibit cytostatic properties, hold significant promise in this area. This review evaluates the anticancer properties of three natural alkaloids-berberine, sanguinarine, and chelerythrine-against CRC and GC. In vivo and in vitro studies have demonstrated that these substances can reduce tumor volume and inhibit the epithelial-mesenchymal transition (EMT) of tumors. At the molecular level, these alkaloids disrupt key signaling pathways in cancer cells, including mTOR, MAPK, EGFR, PI3K/AKT, and NF-κB. Additionally, they exhibit immunomodulatory effects, leading to the induction of programmed cell death through both apoptosis and autophagy. Notably, these substances have shown synergistic effects when combined with classical cytostatic agents such as cyclophosphamide, 5-fluorouracil, cetuximab, and erlotinib. Furthermore, berberine has demonstrated the ability to restore sensitivity in individuals originally resistant to cisplatin GC. Given these findings, natural compounds emerge as a promising option in the chemotherapy of malignant gastrointestinal tumors, particularly in cases with limited treatment options. However, more research is necessary to fully understand their therapeutic potential.
Asunto(s)
Benzofenantridinas , Berberina , Neoplasias Colorrectales , Neoplasias Gástricas , Humanos , Benzofenantridinas/farmacología , Benzofenantridinas/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Berberina/farmacología , Berberina/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Animales , Isoquinolinas/farmacología , Isoquinolinas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Alcaloides/farmacología , Alcaloides/uso terapéuticoRESUMEN
The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity (KD approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a KD of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.
Asunto(s)
Berberina , G-Cuádruplex , Berberina/química , Berberina/análogos & derivados , Berberina/farmacología , Humanos , ADN/química , Ácidos Nucleicos de Péptidos/químicaRESUMEN
Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.
Asunto(s)
Antibacterianos , Berberina , Aprendizaje Profundo , Helicobacter pylori , Helicobacter pylori/efectos de los fármacos , Berberina/farmacología , Berberina/química , Berberina/farmacocinética , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Animales , Omeprazol/farmacología , Claritromicina/farmacología , Amoxicilina/farmacologíaRESUMEN
OBJECTIVE: To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism. METHODS: Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue. RESULTS: After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and severe damage to the tight junction complex structure of intestinal epithelial cells, which was significantly improved in the Ber group but less improved in the DAPT group. The levels of serum DAO, iFABP, TNF-α, IL-6 in the LPS group were significantly higher than those in the Sham group, while the above indicators in the Ber group were significantly lower than those in the LPS group [DAO (µg/L): 4.94±0.44 vs. 6.53±0.49, iFABP (ng/L): 709.67±176.97 vs. 1 417.71±431.44, TNF-α (ng/L): 74.70±8.15 vs. 110.36±3.51, IL-6 (ng/L): 77.34±9.80 vs. 101.65±6.92, all P < 0.01], while the above indicators in the DAPT group were significantly higher than those in the Ber group. The results of RT-PCR and Western blotting showed that the mRNA and protein expressions of Occludin, Claudin1, Notch1, and Hes1 in the ileum tissue of LPS group rats were decreased compared to the Sham group, which were significantly increased in the Ber group compared with the LPS group [mRNA expression: Occludin mRNA (2-ΔΔCt): 1.61±0.74 vs. 0.30±0.12, Claudin1 mRNA (2-ΔΔCt): 1.97±0.37 vs. 0.58±0.14, Notch1 mRNA (2-ΔΔCt): 1.29±0.29 vs. 0.36±0.10, Hes1 mRNA (2-ΔΔCt): 1.22±0.39 vs. 0.27±0.04; protein expression: Occludin/GAPDH: 1.17±0.14 vs. 0.74±0.04, Claudin1/GAPDH: 1.14±0.06 vs. 0.58±0.10, Notch1/GAPDH: 0.87±0.11 vs. 0.56±0.09, Hes1/GAPDH: 1.02±0.13 vs. 0.62±0.01; all P < 0.05], while those in the DAPT group were significantly lower than those in the Ber group. CONCLUSIONS: Early use of berberine hydrochloride can significantly improve intestinal mucosal barrier damage in sepsis rats, and its mechanism may be related to inhibiting inflammatory response and regulating the expression of intestinal mechanical barrier tight junction protein through Notch1 signal.
Asunto(s)
Berberina , Mucosa Intestinal , Ratas Sprague-Dawley , Sepsis , Animales , Berberina/farmacología , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Sepsis/complicaciones , Masculino , Ratas , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Transducción de Señal/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Purpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro. Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model. Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2. Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology.
Asunto(s)
Berberina , Colitis Ulcerosa , Biología Computacional , Subunidad alfa del Factor 1 Inducible por Hipoxia , FN-kappa B , Receptor Toll-Like 4 , Berberina/farmacología , Berberina/química , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Animales , Ratones , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Simulación del Acoplamiento Molecular , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Masculino , Sulfato de Dextran , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Farmacología en RedRESUMEN
Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.
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Berberina , Química Farmacéutica , Composición de Medicamentos , Liberación de Fármacos , Excipientes , Tamaño de la Partícula , Solubilidad , Berberina/química , Berberina/administración & dosificación , Berberina/farmacocinética , Excipientes/química , Composición de Medicamentos/métodos , Química Farmacéutica/métodos , Disponibilidad Biológica , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Polvos/química , Difracción de Rayos X/métodos , Rastreo Diferencial de Calorimetría/métodosRESUMEN
Protoplasts are plant cells from which the pectocellulosic cell wall has been removed, thus keeping the plasma membrane intact. For plant secondary metabolites research, this system is a powerful tool to study the metabolites' dynamics inside the cells, such as the subcellular localization of proteins, characterization of gene function, transcription factors involved in metabolite pathways, protein transport machinery, and to perform single-cell omics studies. Due to its lack of a cell wall, better images of the interior of the cell can be obtained compared to the whole tissue. This allows the identification of specific cell types involved in the accumulation of specialized metabolites, such as alkaloids, given their autofluorescence properties. Here is a simplified protocol to obtain protoplasts from leaves and in vitro cell cultures from Argemone mexicana, which produces the pharmacologically important alkaloids berberine and sanguinarine.
Asunto(s)
Alcaloides , Argemone , Plantas Medicinales , Protoplastos , Protoplastos/metabolismo , Argemone/química , Argemone/metabolismo , Plantas Medicinales/metabolismo , Plantas Medicinales/química , Alcaloides/metabolismo , Hojas de la Planta/metabolismo , Benzofenantridinas/metabolismo , Berberina/metabolismo , IsoquinolinasRESUMEN
Antioxidant-rich supplementation plays an essential role in the function of mammals' central nervous system. However, no research has documented the effect of berberine (BER) supplementation on the cerebrocerebellar function of prepubertal rats. The present study was designed to investigate the impact of BER supplementation on neurochemical and behavioural changes in prepubertal male rats. Five groups (90 ± 5 g, n = 7 each) of experimental rats were orally treated with corn oil or different doses of BER (25, 50, 100, and 200 mg/kg bw) from the 28th at 68 post-natal days. On the 69 days of life, animals underwent behavioural assessment in the open field, hanging wire, and negative geotaxis tests. The result revealed that BER administration improved locomotive and motor behaviour by increasing distance travelled, line crossings, average speed, time mobile, and absolute turn angle in open field test and decrease in time to re-orient on an incline plane, a decrease in immobility time relative to the untreated control. Furthermore, BER supplementation increased (p < 0.05) antioxidant enzyme activities such as SOD, CAT, GPx, GSH, and TSH and prevented increases (p < 0.05) in oxidative and inflammatory levels as indicated by decreases in RONS, LPO, XO, carbonyl protein, NO, MPO, and TNF-α compared to the untreated control. BER-treated animals a lessened number of dark-stained Nissl cells compared to the untreated control rats. Our findings revealed that BER minimised neuronal degeneration and lesions, improved animal behaviour, and suppressed oxidative and inflammatory mediators, which may probably occur through its agonistic effect on PPAR-α, PPAR-δ, and PPAR-γ - essential proteins known to resolve inflammation and modulate redox signalling towards antioxidant function.
Asunto(s)
Antioxidantes , Berberina , Ratas Wistar , Animales , Masculino , Ratas , Berberina/farmacología , Berberina/administración & dosificación , Antioxidantes/farmacología , Antioxidantes/metabolismo , Cerebelo/metabolismo , Cerebelo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Glutatión/metabolismo , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismoRESUMEN
Globally, the metabolic dysfunction-associated fatty liver disease (MAFLD) holds the position as the most widespread chronic liver condition. Berberine (BBR) shows promise as a natural compound for managing obesity, hepatic steatosis, and metabolic disorders. The study aimed to investigate the effectiveness of BBR in addressing factors linked to MAFLD. This is a randomized, double-blind, and placebo-controlled clinical trial. Seventy individuals with MAFLD were enrolled in this study and randomly assigned in a 1:1 ratio to two groups. BBR (1500 mg/day) or placebo was administrated orally for 12 weeks. Selected anthropometric, hepatic, and metabolic parameters were assessed. After a 12-week intervention, the BBR group demonstrated a statistically significant decrease in alanine transaminase (ALT) p=0.0105, and de Ritis ratio p=0.0011 compared to the control group. In both groups we observed a decrease in trunk fat (kg) - BBR group p=0.0185, and placebo group p=0.0323. After three months, a significant divergence between the BBR and placebo groups was evident in the alteration of Δ total cholesterol (TC) p=0.0009, favoring the BBR group. Nevertheless, there were no significant differences detected in other lipid and glucose parameters. In the BBR group, we found significant correlations between changes and amelioration of certain variables: Δ body mass index (BMI) correlated with ΔALT (r=0.47; p=0.0089) and D aspartate aminotransferase (AST) (r=0.47; p=0.0081) levels; Δ trunk fat with Δ fatty liver index (FLI) (r=0.55; p=0.0337), Δ homeostasis model assessment for insulin resistant index (HOMA-IR) (r=0.37; p=0.0020), and AST (r=0.42; p=0.0202); D the de Ritis ratio correlated with Δ fibrosis-4 index (FIB-4) levels (r=0.59; p=0.0011); and ΔFLI correlated with ΔHOMA-IR (r=0.37; p=0.0409) and Δ visceral adiposity index (VAI) (r=0.54; p=0.0019), while no significant differences were observed in the Placebo group. The results show that BBR appears to be a bioactive compound that positively impacts MAFLD, however, additional research with extended intervention durations is required to fully assess its efficacy and potential clinical use.
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Berberina , Hígado , Humanos , Berberina/uso terapéutico , Berberina/farmacología , Método Doble Ciego , Masculino , Femenino , Persona de Mediana Edad , Adulto , Hígado/metabolismo , Hígado/efectos de los fármacos , Alanina Transaminasa/sangre , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , AntropometríaRESUMEN
Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expressions were determined in heart tissue. The CYP group's troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-ß1 and α-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-ß1, FSP1 and α-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage.
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Berberina , Curcumina , Ciclofosfamida , Fibrosis , Miocardio , Canales Catiónicos TRPM , Animales , Canales Catiónicos TRPM/metabolismo , Ciclofosfamida/toxicidad , Ciclofosfamida/efectos adversos , Masculino , Ratas , Curcumina/farmacología , Berberina/farmacología , Miocardio/metabolismo , Miocardio/patología , Biomarcadores/metabolismo , Biomarcadores/sangre , Lípidos/sangre , Ratas Wistar , Cardiopatías/inducido químicamente , Cardiopatías/metabolismo , Cardiopatías/patología , Cardiopatías/prevención & control , Cardiopatías/tratamiento farmacológicoRESUMEN
BACKGROUND: Berberine (BBR), a key component in Kampo medicine, is a cationic benzylisoquinoline alkaloid whose detection plays a critical role in the quality control of these traditional remedies. Traditional methods for detecting BBR often involve complex procedures, which can be time-consuming and costly. To address this challenge, our study focuses on developing a simpler, faster, and more efficient detection method for BBR in Kampo medicine formulations. RESULTS: We successfully developed a rapid fluorometric detection method for BBR using colloidal gold nanoparticle-based systematic evolution of ligands by exponential enrichment (GOLD-SELEX). Initially, specific single-stranded DNA (ssDNA) sequences were selected for their ability to enhance BBR's fluorescence intensity. The optimal ssDNA sequence, identified as BBR38, was further truncated to produce BBR38S, a stem-loop ssDNA that improved fluorescence upon interaction with BBR. To further enhance the fluorescence, the BBR38S aptamer underwent additional modifications, including stem truncation and nucleotide mutations, resulting in the higher fluorescence variant BBR38S-3 A10C. The final product, TetBBR38S, a tetramer version of BBR38S-3 A10C, exhibited a linear detection range of 0.780-50.0 µg mL-1 and a limit of detection of 0.369 µg mL-1. The assay demonstrated sufficient selectivity and was successfully applied to analyze 128 different Kampo medicine formulations, accurately detecting BBR content with high precision. SIGNIFICANCE: This study represents an advancement in Kampo medicine research, marking the first successful application of an aptamer-based approach for BBR detection in complex matrices. The developed method is not only simple and rapid (with a detection time of 5 min) but also cost-effective, which is crucial for widespread application.
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Aptámeros de Nucleótidos , Berberina , Fluorometría , Medicina Kampo , Berberina/química , Berberina/análisis , Aptámeros de Nucleótidos/química , Fluorometría/métodos , Técnica SELEX de Producción de Aptámeros/métodos , Límite de Detección , Nanopartículas del Metal/química , Oro/química , ADN de Cadena Simple/químicaRESUMEN
Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.
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Adipoquinas , Berberina , Composición Corporal , Gymnema sylvestre , Obesidad , Resistina , Humanos , Masculino , Femenino , Adulto , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Adipoquinas/sangre , Adipoquinas/metabolismo , Composición Corporal/efectos de los fármacos , Persona de Mediana Edad , Berberina/farmacología , Resistina/sangre , Resistina/metabolismo , Apelina , Presión Sanguínea/efectos de los fármacos , Nicotinamida Fosforribosiltransferasa/metabolismo , Citocinas/metabolismo , Citocinas/sangre , Extractos Vegetales/farmacología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Lectinas , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéuticoRESUMEN
BACKGROUND: The prevention of obesity represents a major health and socio-economic challenge. Nutraceuticals are regularly highlighted for their beneficial effects in preventing the metabolic disturbances associated with obesity. However, few studies have described the combined action of nutraceutical mixtures combining polyphenols with alkaloids. OBJECTIVE: The aim of this study was to evaluate the effects of long-term dietary supplementation with a mixture of Berberine, Citrus and Apple extracts (BCA) in the primary prevention of obesity and its metabolic and vascular complications in the obese Zucker rat, a spontaneous model of genetic obesity and insulin resistance. METHODS: Sixteen 8-week-old obese Zucker male rats were randomly divided into two groups: all rats received oral gavage daily either with water, untreated obese (U-ObZ) or BCA (BCA-ObZ) mixture for thirteen weeks. Morphological and metabolic parameters were measured along the study. Cumulative concentration-response curves to insulin, acetylcholine and phenylephrine were determined on isolated thoracic aorta. Colon permeability measurements were performed using the Ussing chamber technique. Fecal samples collected at the beginning and the end of the protocol were used as a template for amplification of the V3-V4 region of the 16S rDNA genes. RESULTS: BCA supplementation reduced weight gain (p<0.05) and food intake (p<0.05) in the BCA-ObZ group rats compared to the U-ObZ group rats. It also improved glucose tolerance (p<0.001) and decreased fasting insulin and Homeostasis model assessment index (p<0.05). Through ex vivo experiments, the BCA mixture enhanced significantly aortic insulin relaxation (p<0.01), reduced α1-adrenoceptor-mediated vasoconstriction (p<0.01), and decreased distal colon permeability. Moreover, short-chain fatty acid producers such as Bacteroides, Blautia, and Akkermansia were found to be increased by the BCA mixture supplementation. CONCLUSION: The results showed that a 13-week-supplementation with BCA mixture prevented weight gain and improved glucose metabolism in obese Zucker rats. We also demonstrated that BCA supplementation improved vascular function, colonic barrier permeability and gut microbiota profile.
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Berberina , Citrus , Suplementos Dietéticos , Malus , Obesidad , Extractos Vegetales , Ratas Zucker , Animales , Berberina/farmacología , Berberina/uso terapéutico , Masculino , Obesidad/metabolismo , Obesidad/prevención & control , Obesidad/tratamiento farmacológico , Ratas , Citrus/química , Extractos Vegetales/farmacología , Malus/química , Resistencia a la Insulina , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Insulina/sangre , Insulina/metabolismoRESUMEN
Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.
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Alimentación Animal , Berberina , Pollos , Microbioma Gastrointestinal , Enfermedades de las Aves de Corral , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Femenino , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/prevención & control , Alimentación Animal/análisis , Berberina/farmacología , Berberina/administración & dosificación , Dieta con Restricción de Proteínas/veterinaria , Metabolómica , Hígado Graso/veterinaria , Metabolismo de los Lípidos/efectos de los fármacos , Suplementos Dietéticos/análisisRESUMEN
The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0-2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6-12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12_18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12_18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12_18892 to regulate the expression of adcy3 and participate in glucose metabolism.