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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731953

RESUMO

Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system.


Assuntos
Apoptose , Berberina , Caquexia , Proteína HMGB1 , Animais , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Berberina/farmacologia , Ratos , Caquexia/metabolismo , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Autofagia/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Masculino , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Ratos Sprague-Dawley , Neoplasias/metabolismo , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/patologia , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
2.
Toxicol Appl Pharmacol ; 486: 116952, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38705399

RESUMO

The incidence of contrast-induced acute kidney injury (CI-AKI) has escalated to become the third most prevalent cause of hospital-acquired AKI, with a lack of efficacious interventions. Berberine (BBR) possesses diverse pharmacological effects and exhibits renoprotective properties; however, limited knowledge exists regarding its impact on CI-AKI. Therefore, our study aimed to investigate the protective effects and underlying mechanisms of BBR on CI-AKI in a mice model, focusing on the nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3) inflammasome and mitophagy. The CI-AKI mice model was established by administering NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg), indomethacin (10 mg/kg), and iohexol (11 g/kg) following water deprivation. A pretreatment of 100 mg/kg of BBR was orally administered to the mice for two weeks. Renal injury markers, damage-associated molecular patterns (DAMPs), renal histopathology, mitochondrial morphology, autophagosomes, and potential mechanisms were investigated. BBR effectively reduced levels of renal injury biomarkers such as serum cystatin C, urea nitrogen, and creatinine, downregulated the protein level of kidney injury molecule 1 (KIM1), and mitigated renal histomorphological damage. Moreover, BBR reduced DAMPs, including high mobility group box-1 (HMGB1), heat shock protein 70 (HSP70), and uric acid (UA). It also alleviated oxidative stress and inflammatory factors such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß). Furthermore, the activation of NLRP3 inflammasome was attenuated in the BBR pretreatment group, as evidenced by both mRNA and protein levels. Electron microscopy and western blotting examination revealed that BBR mitigated mitochondrial damage and enhanced mitophagy. Additionally, BBR increased the P-AMPK/AMPK ratio. These findings indicated that BBR exerted a protective effect against CI-AKI by suppressing NLRP3 inflammasome activation and modulating mitophagy, providing a potential therapeutic strategy for its prevention.


Assuntos
Injúria Renal Aguda , Berberina , Meios de Contraste , Modelos Animais de Doenças , Inflamassomos , Camundongos Endogâmicos C57BL , Mitofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mitofagia/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Camundongos , Berberina/farmacologia , Masculino , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo
3.
Sci Rep ; 14(1): 11999, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796469

RESUMO

Allergic rhinitis is a prevalent inflammatory condition that impacts individuals of all age groups. Despite reports indicating the potential of berberine in alleviating allergic rhinitis symptoms, the specific molecular mechanisms and therapeutic targets of berberine remain unclear. This research aims to explore the pharmacological mechanism of berberine in the treatment of allergic rhinitis through bioinformatic analyses and experimental validation. The research utilized public databases to identify potential targets of berberine. Furthermore, differentially expressed genes (DEGs) related to allergic rhinitis were pinpointed from the GSE52804 dataset. Through bioinformatics techniques, the primary targets were discovered and key KEGG and GO-BP pathways were established. To confirm the therapeutic mechanisms of berberine on allergic rhinitis, an OVA-induced allergic rhinitis model was developed using guinea pigs. We identified 32 key genes responsible for the effectiveness of berberine in treating allergic rhinitis. In addition, five central genes (Alb, Il6, Tlr4, Ptas2, and Il1b) were pinpointed. Further examination using KEGG and GO-BP pathways revealed that the main targets were primarily involved in pathways such as NF-kappa B, IL-17, TNF, and inflammatory response. Molecular docking analysis demonstrated that berberine exhibited strong affinity towards these five key targets. Furthermore, the expression levels of IL-6, TLR4, PTGS2, and IL-1ß were significantly upregulated in the model group but downregulated following berberine treatment. This research has revealed the mechanism through which berberine combats allergic rhinitis and has identified its potential to regulate pathways linked to inflammation. These discoveries provide valuable insights for the development of novel medications for the treatment of allergic rhinitis.


Assuntos
Berberina , Biologia Computacional , Simulação de Acoplamento Molecular , Rinite Alérgica , Berberina/farmacologia , Berberina/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/genética , Rinite Alérgica/metabolismo , Animais , Cobaias , Biologia Computacional/métodos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Masculino , Ovalbumina
4.
J Ethnopharmacol ; 331: 118305, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38729536

RESUMO

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


Assuntos
Candida albicans , Candidíase Bucal , Medicamentos de Ervas Chinesas , Células Epiteliais , Receptores ErbB , Receptores ErbB/metabolismo , Animais , Medicamentos de Ervas Chinesas/farmacologia , Candidíase Bucal/tratamento farmacológico , Candida albicans/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Berberina/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Camundongos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiologia , Antifúngicos/farmacologia , Masculino , Linhagem Celular , Transdução de Sinais/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Coptis chinensis
5.
Cell Biochem Funct ; 42(4): e4033, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38742849

RESUMO

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi-step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology.


Assuntos
Berberina , Neoplasias Colorretais , Berberina/farmacologia , Berberina/uso terapêutico , Humanos , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos
6.
BMC Oral Health ; 24(1): 530, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704553

RESUMO

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


Assuntos
Berberina , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Periodontite , Humanos , Periodontite/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Berberina/farmacologia , Berberina/uso terapêutico , Coptis chinensis , Rizoma , Interleucina-17/metabolismo , Transdução de Sinais/efeitos dos fármacos , Técnicas In Vitro , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo
7.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38673787

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.


Assuntos
Berberina , Hepatopatia Gordurosa não Alcoólica , Berberina/farmacologia , Berberina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Humanos , Animais , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos
8.
J Ethnopharmacol ; 331: 118263, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38677575

RESUMO

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.


Assuntos
Berberina , Coptis chinensis , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Hiperlipidemias , Scutellaria baicalensis , Animais , Hiperlipidemias/tratamento farmacológico , Scutellaria baicalensis/química , Masculino , Berberina/farmacologia , Berberina/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Flavonoides/farmacologia , Camundongos Endogâmicos C57BL , Família 4 do Citocromo P450/genética , Família 4 do Citocromo P450/metabolismo , Coptis/química , Hipolipemiantes/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lipídeos/sangue , Modelos Animais de Doenças , Rizoma
9.
Appl Microbiol Biotechnol ; 108(1): 289, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587649

RESUMO

Rumen microbial urease inhibitors have been proposed for regulating nitrogen emission and improving nitrogen utilization efficiency in ruminant livestock industry. However, studies on plant-derived natural inhibitors of rumen microbial urease are limited. Urease accessory protein UreG, plays a crucial role in facilitating urease maturation, is a new target for design of urease inhibitor. The objective of this study was to select the potential effective inhibitor of rumen microbial urease from major protoberberine alkaloids in Rhizoma Coptidis by targeting UreG. Our results showed that berberine chloride and epiberberine exerted superior inhibition potential than other alkaloids based on GTPase activity study of UreG. Berberine chloride inhibition of UreG was mixed type, while inhibition kinetics type of epiberberine was uncompetitive. Furthermore, epiberberine was found to be more effective than berberine chloride in inhibiting the combination of nickel towards UreG and inducing changes in the second structure of UreG. Molecular modeling provided the rational structural basis for the higher inhibition potential of epiberberine, amino acid residues in G1 motif and G3 motif of UreG formed interactions with D ring of berberine chloride, while interacted with A ring and D ring of epiberberine. We further demonstrated the efficacy of epiberberine in the ruminal microbial fermentation with low ammonia release and urea degradation. In conclusion, our study clearly indicates that epiberberine is a promising candidate as a safe and effective inhibitor of rumen microbial urease and provides an optimal strategy and suitable feed additive for regulating nitrogen excretion in ruminants in the future. KEY POINTS: • Epiberberine is the most effective inhibitor of rumen urease from Rhizoma Coptidis. • Urease accessory protein UreG is an effective target for design of urease inhibitor. • Epiberberine may be used as natural feed additive to reducing NH3 release in ruminants.


Assuntos
Berberina , Berberina/análogos & derivados , Animais , Berberina/farmacologia , Urease , Amônia , Cloretos , Rúmen , Inibidores Enzimáticos/farmacologia , Nitrogênio , Ruminantes
10.
Int J Mol Med ; 53(5)2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38577949

RESUMO

Several studies have shown that berberine (BBR) is effective in protecting against myocardial ischemia­reperfusion injury (MI/RI). However, the precise molecular mechanism remains elusive. The present study observed the mechanism and the safeguarding effect of BBR against hypoxia/reoxygenation (H/R) myocardial injury in H9c2 cells. BBR pretreatment significantly improved the decrease of cell viability, P62 protein, Rho Family GTPase 3 (RhoE) protein, ubiquinone subunit B8 protein, ubiquinol­cytochrome c reductase core protein U, the Bcl­2­associated X protein/B­cell lymphoma 2 ratio, glutathione (GSH) and the GSH/glutathione disulphide (GSSG) ratio induced by H/R, while reducing the increase in lactate dehydrogenase, microtubule­associated protein 1 light 3 protein, caspase­3 activity, reactive oxygen species, GSSG and malonaldehyde caused by H/R. Transmission electron microscopy and LysoTracker Red DND­99 staining results showed that BBR pretreatment inhibited H/R­induced excessive autophagy by mediating RhoE. BBR also inhibited mitochondrial permeability transition, maintained the stability of the mitochondrial membrane potential, reduced the apoptotic rate, and increased the level of caspase­3. However, the protective effects of BBR were attenuated by pAD/RhoE­small hairpin RNA, rapamycin (an autophagy activator) and compound C (an AMP­activated protein kinase inhibitor). These new findings suggested that BBR protects the myocardium from MI/RI by inhibiting excessive autophagy, maintaining mitochondrial function, improving the energy supply and redox homeostasis, and attenuating apoptosis through the RhoE/AMP­activated protein kinase pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Autofagia , Berberina , Traumatismo por Reperfusão Miocárdica , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose , Berberina/farmacologia , Caspase 3/metabolismo , Dissulfeto de Glutationa/metabolismo , Isquemia/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/etiologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Animais , Ratos
11.
Molecules ; 29(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38611845

RESUMO

In this paper, berberine hydrochloride-loaded liposomes-in-gel were designed and developed to investigate their antioxidant properties and therapeutic effects on the eczema model of the mouse. Berberine hydrochloride-liposomes (BBH-L) as the nanoparticles were prepared by the thin-film hydration method and then dispersed BBH-L evenly in the gel matrix to prepare the berberine hydrochloride liposomes-gel (BBH-L-Gel) by the natural swelling method. Their antioxidant capacity was investigated by the free radical scavenging ability on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and H2O2 and the inhibition of lipid peroxides malondialdehyde (MDA). An eczema model was established, and the efficacy of the eczema treatment was preliminarily evaluated using ear swelling, the spleen index, and pathological sections as indicators. The results indicate that the entrapment efficiency of BBH-L prepared by the thin-film hydration method was 78.56% ± 0.7%, with a particle size of 155.4 ± 9.3 nm. For BBH-L-Gel, the viscosity and pH were 18.16 ± 6.34 m Pas and 7.32 ± 0.08, respectively. The cumulative release in the unit area of the in vitro transdermal study was 85.01 ± 4.53 µg/cm2. BBH-L-Gel had a good scavenging capacity on DPPH and H2O2, and it could effectively inhibit the production of hepatic lipid peroxides MDA in the concentration range of 0.4-2.0 mg/mL. The topical application of BBH-L-Gel could effectively alleviate eczema symptoms and reduce oxidative stress injury in mice. This study demonstrates that BBH-L-Gel has good skin permeability, excellent sustained release, and antioxidant capabilities. They can effectively alleviate the itching, inflammation, and allergic symptoms caused by eczema, providing a new strategy for clinical applications in eczema treatment.


Assuntos
Berberina , Eczema , Animais , Camundongos , Antioxidantes/farmacologia , Berberina/farmacologia , Lipossomos , Peróxido de Hidrogênio , Peróxidos Lipídicos
12.
Molecules ; 29(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38611885

RESUMO

Mesoporous titanium nanoparticles (MTN) have always been a concern and are considered to have great potential for overcoming antibiotic-resistant bacteria. In our study, MTN modified with functionalized UV-responsive ethylene imine polymer (PEI) was synthesized. The characterization of all products was performed by different analyses, including SEM, TEM, FT-IR, TGA, XRD, XPS, and N2 adsorption-desorption isotherms. The typical antibacterial drug berberine hydrochloride (BH) was encapsulated in MTN-PEI. The process exhibited a high drug loading capacity (22.71 ± 1.12%) and encapsulation rate (46.56 ± 0.52%) due to its high specific surface area of 238.43 m2/g. Moreover, UV-controlled drug release was achieved by utilizing the photocatalytic performance of MTN. The antibacterial effect of BH@MTN-PEI was investigated, which showed that it could be controlled to release BH and achieve a corresponding antibacterial effect by UV illumination for different lengths of time, with bacterial lethality reaching 37.76% after only 8 min of irradiation. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the nanoparticles have also been studied. The MIC of BH@MTN-PEI was confirmed as 1 mg/mL against Escherichia coli (E. coli), at which the growth of bacteria was completely inhibited during 24 h and the concentration of 5 mg/mL for BH@MTN-PEI was regarded as MBC against E. coli. Although this proof-of-concept study is far from a real-life application, it provides a possible route to the discovery and application of antimicrobial drugs.


Assuntos
Berberina , Nanopartículas , Berberina/farmacologia , Liberação Controlada de Fármacos , Escherichia coli , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio/farmacologia , Antibacterianos/farmacologia
13.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612606

RESUMO

Vulvovaginal candidiasis (VVC) is a real gynecological problem among women of reproductive age from 15 to 49. A recent analysis showed that 75% of women will have an occurrence at least once per year, while 5% are observed to have recurrent vaginal mycosis-these patients may become unwell four or more times a year. This pathology is caused in 85-90% of cases by fungi of the Candida albicans species. It represents an intractable medical problem for female patients due to pain and pruritus. Due to the observation of an increasing number of strains resistant to standard preparations and an increase in the recurrence of this pathology when using local or oral preferential therapy, such as fluconazole, an analysis was launched to develop alternative methods of treating VVC using herbs such as dill, turmeric, and berberine. An in-depth analysis of databases that include scientific articles from recent years made it possible to draw satisfactory conclusions supporting the validity of herbal therapy for the pathology in question. Although phytotherapy has not yet been approved by the Food and Drug Administration, it appears to be a promising therapeutic solution for strains that are resistant to existing treatments. There is research currently undergoing aimed at comparing classical pharmacotherapy and herbal therapy in the treatment of vaginal candidiasis for the purpose of increasing medical competence and knowledge for the care of the health and long-term comfort of gynecological patients.


Assuntos
Berberina , Candidíase Vulvovaginal , Estados Unidos , Humanos , Feminino , Candidíase Vulvovaginal/tratamento farmacológico , Fitoterapia , Candida , Vagina
14.
Anal Chim Acta ; 1304: 342579, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38637044

RESUMO

Plasmon enhanced fluorescent (PEF) with more "hot spots" play a critical role in signal amplified technology to avoid the intrinsic limitation of fluorophore which ascribed to a strong electromagnetic field at the tip structure. However, application of PEF technique to obtain a highly sensitive analysis of medicine was still at a very early stage. Herein, a simple but versatile Ag nanocubes (Agcubes)-based PEF sensor combined with aptamer (Agcubes@SiO2-QDs-Apt) was proposed for highly sensitive detection of berberine hydrochloride (BH). The distance between the plasma Agcubes and the red-emitted CdTe quantum dots (QDs) were regulated by the thickness of silica spacer. The three-dimensional finite-difference time-domain (3D-FDTD) simulation further revealed that Agcubes have a higher electromagnetic field than Ag nanospheres. Compared with PEF sensor, signal QDs-modified aptamer without Agcubes (QDs-Apt) showed a 10-fold higher detection limit. The linear range and detection limit of the Agcubes@SiO2-QDs-Apt were 0.1-100 µM, 87.3 nM, respectively. Furthermore, the PEF sensor was applied to analysis BH in the berberine hydrochloride tablets, compound berberine tablet and urine with good recoveries of 98.25-102.05%. These results demonstrated that the prepared PEF sensor has great potential for drug quality control and clinical analysis.


Assuntos
Aptâmeros de Nucleotídeos , Berberina , Compostos de Cádmio , Pontos Quânticos , Fluorescência , Pontos Quânticos/química , Compostos de Cádmio/química , Dióxido de Silício , Telúrio/química , Espectrometria de Fluorescência/métodos , Aptâmeros de Nucleotídeos/química , Limite de Detecção
15.
Sci Rep ; 14(1): 9381, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654085

RESUMO

Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined. Drug loading was optimized for the study using Taguchi experimental design and lab experiments. Loaded erythrocytes were targeted to macrophages using ZnCl2 and bis-sulfosuccinimidyl-suberate, and targeting was evaluated using flow cytometry and Wright-Giemsa staining. Differentiated macrophages were stimulated with lipopolysaccharide, and the inflammatory profiles of macrophages were evaluated using ELISA, western blotting, and real-time PCR. Findings indicated that the endocytosis method is preferred due to its low impact on the erythrocyte's structural integrity. Maximum loading achieved (1386.68 ± 22.43 µg/ml) at 1500 µg/ml berberine treatment at 37 °C for 2 h. Berberine successfully inhibited NF-κB translation in macrophages, and inflammatory response markers such as IL-1ß, IL-8, IL-23, and TNF-α were decreased by approximately ninefold, sixfold, twofold, eightfold, and twofold, respectively, compared to the LPS-treated macrophages. It was concluded that berberine-loaded erythrocytes can effectively target macrophages and modulate the inflammatory response.


Assuntos
Berberina , Citocinas , Eritrócitos , Macrófagos , Berberina/farmacologia , Berberina/administração & dosagem , Eritrócitos/metabolismo , Eritrócitos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Citocinas/metabolismo , Animais , Camundongos , Lipopolissacarídeos/farmacologia , Células RAW 264.7 , NF-kappa B/metabolismo , Inflamação/metabolismo , Inflamação/tratamento farmacológico
16.
Biol Pharm Bull ; 47(4): 827-839, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599826

RESUMO

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


Assuntos
Berberina , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Berberina/análogos & derivados , Estudos de Casos e Controles , Coptis chinensis , Neurônios Dopaminérgicos/metabolismo , Mutação , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Rizoma
17.
Int J Pharm ; 656: 124051, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38574956

RESUMO

The use of berberine hydrochloride (BCS class III) has limited application in psoriasis, when given as topical drug delivery systems, due to low permeability in the skin layer. Hence, berberine hydrochloride-loaded aquasome nanocarriers were developed for skin targeting, particularly epidermis (primary site of psoriasis pathophysiology) and enhance the skin permeability of berberine hydrochloride. Aquasomes were formulated using the adsorption method and characterized by structural morphology TEM, % drug adsorption, drug release profile (in-vitro and ex-vivo), in-vivo efficacy study and stability study. The reduced particle size and higher surface charge of SKF3 formulation (263.57 ± 27.78 nm and -21.0 ± 0.43 mV) showed improved stability of aquasomes because of the development of higher surface resistance to formation of aggregates. The adsorption of hydrophilic berberine and the non-lipidic nature of aquasomes resulted in % adsorption efficiency (%AE) of 94.46 ± 0.39 %. The controlled first-order release behavior of aquasomes was reported to be 52.647 ± 14.63 and 32.08 ± 12.78 % in in-vitro and ex-vivo studies, respectively. In-vivo studies demonstrated that topical application of berberine hydrochloride loaded aquasomes significantly alleviated psoriasis symptoms like hyperkeratosis, scaling and inflammation, due to the reduction in the inflammatory cytokines (IL-17 and IL-23). Therefore, aquasome formulation exhibits an innovative approach for targeted application of berberine hydrochloride in the management of psoriasis.


Assuntos
Administração Cutânea , Berberina , Epiderme , Psoríase , Absorção Cutânea , Berberina/administração & dosagem , Berberina/farmacocinética , Berberina/química , Psoríase/tratamento farmacológico , Animais , Epiderme/metabolismo , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Masculino , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Nanopartículas/administração & dosagem , Tamanho da Partícula , Permeabilidade , Ratos , Estabilidade de Medicamentos
18.
Behav Brain Res ; 466: 114981, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38580198

RESUMO

This study verified the effects of the natural compounds berberine and hesperidin on seizure development and cognitive impairment triggered by pentylenetetrazole (PTZ) in zebrafish. Adult animals were submitted to a training session in the inhibitory avoidance test and, after 10 minutes, they received an intraperitoneal injection of 25, 50, or 100 mg/kg berberine or 100 or 200 mg/kg hesperidin. After 30 minutes, the animals were exposed to 7.5 mM PTZ for 10 minutes. Animals were submitted to the test session 24 h after the training session to verify their cognitive performance. Zebrafish larvae were exposed to 100 µM or 500 µM berberine or 10 µM or 50 µM hesperidin for 30 minutes. After, larvae were exposed to PTZ and had the seizure development evaluated by latency to reach the seizure stages I, II, and III. Adult zebrafish pretreated with 50 mg/kg berberine showed a longer latency to reach stage III. Zebrafish larvae pretreated with 500 µM berberine showed a longer latency to reach stages II and III. Hesperidin did not show any effect on seizure development both in larvae and adult zebrafish. Berberine and hesperidin pretreatments prevented the memory consolidation impairment provoked by PTZ-induced seizures. There were no changes in the distance traveled in adult zebrafish pretreated with berberine or hesperidin. In larval stage, berberine caused no changes in the distance traveled; however, hesperidin increased the locomotion. Our results reinforce the need for investigating new therapeutic alternatives for epilepsy and its comorbidities.


Assuntos
Aprendizagem da Esquiva , Berberina , Hesperidina , Pentilenotetrazol , Convulsões , Peixe-Zebra , Animais , Pentilenotetrazol/farmacologia , Berberina/farmacologia , Berberina/administração & dosagem , Hesperidina/farmacologia , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Aprendizagem da Esquiva/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , Masculino , Modelos Animais de Doenças , Convulsivantes/farmacologia , Larva/efeitos dos fármacos , Relação Dose-Resposta a Droga , Anticonvulsivantes/farmacologia
19.
J Nat Med ; 78(3): 590-598, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38573419

RESUMO

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.


Assuntos
Berberina , Flavonoides , Berberina/química , Berberina/análogos & derivados , Flavonoides/química , Alcaloides de Berberina/química , Coptis/química , Água/química , Estrutura Molecular , Rizoma/química
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 639-642, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660879

RESUMO

Berberine, a traditional Chinese medicine, is an isoquinoline alkaloid extracted from the rhizome of Coptis chinensis. It has anti-inflammatory and antidiarrheal effects and is commonly used in the treatment of infections and gastrointestinal diseases. In recent years, studies have found that berberine can play a wide range of anti-cancer effects in the treatment of leukemia, lymphoma, multiple myeloma, etc. In hematologic malignancies, berberine can induce autophagy, promote apoptosis, regulate cell cycle, inhibit inflammatory response, cause oxidative damage to cancer cells and interact with miRNA to inhibit the proliferation, migration and colony formation of cancer cells. This paper will review the role and related mechanisms of berberine in hematological malignancies.


Assuntos
Apoptose , Berberina , Neoplasias Hematológicas , Berberina/farmacologia , Humanos , Neoplasias Hematológicas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , MicroRNAs
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