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1.
Front Immunol ; 12: 656419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745081

RESUMO

Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function. Here, we investigated the adjunct therapy of natural immune-modulatory compound berberine in C57BL/6 mouse model of pulmonary TB. Berberine treatment did not affect Mtb growth in axenic cultures; however, it showed increased bacterial killing in primary murine bone marrow-derived macrophages and human monocyte-derived macrophages. Ad libitum berberine administration was beneficial to the host in combination with rifampicin and isoniazid. Berberine adjunctive treatment resulted in decreased lung pathology with no additive or synergistic effects on bacterial burdens in mice. Lung immune cell flow cytometry analysis showed that adjunctive berberine treatment decreased neutrophil, CD11b+ dendritic cell and recruited interstitial macrophage numbers. Late onset of adjunctive berberine treatment resulted in a similar phenotype with consistently reduced numbers of neutrophils both in lungs and the spleen. Together, our results suggest that berberine can be supplemented as an immunomodulatory agent depending on the disease stage and inflammatory status of the host.


Assuntos
Antituberculosos/uso terapêutico , Berberina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Isoniazida/uso terapêutico , Rifampina/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Animais , Antituberculosos/farmacologia , Berberina/farmacologia , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/farmacologia , Isoniazida/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Rifampina/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/microbiologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
2.
Molecules ; 26(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34684819

RESUMO

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.


Assuntos
Berberina/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamação/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Humanos , Inflamassomos/química , Inflamação/metabolismo , Doenças Metabólicas/tratamento farmacológico , Modelos Biológicos , Proteína 3 que Contém Domínio de Pirina da Família NLR/química , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Compostos Fitoquímicos/farmacologia , Fitoterapia , Transdução de Sinais/efeitos dos fármacos
3.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641542

RESUMO

Cancer is the second leading cause of death in the world. Chemotherapy and radiotherapy (RT) are the common cancer treatments. In addition to these limitations, the development of adverse effects from chemotherapy and RT reduces the quality of life for cancer patients. Cellular radiosensitivity, or the ability to resist and overcome cell damage caused by ionizing radiation (IR), is directly related to cancer cells' response to RT. Therefore, radiobiological research is emphasizing chemical compounds 'radiosensitization of cancer cells so that they are more reactive in the IR spectrum. Recent years researchers have seen an increase in interest in natural products that have antitumor effects with minimal side effects. Natural products, on the other hand, are easy to recover and therefore less expensive. There have been several scientific studies done based on these compounds that have tested their ability in vitro and in vivo to induce tumor radiosensitization. The role of natural products in RT, as well as their usefulness and potential applications, is the goal of this current review.


Assuntos
Produtos Biológicos/farmacologia , Radioterapia/efeitos adversos , Berberina/farmacologia , Curcumina/farmacologia , Emodina/farmacologia , Genisteína/farmacologia , Humanos , Neoplasias/radioterapia , Triterpenos Pentacíclicos/farmacologia , Protetores contra Radiação/farmacologia , Radiossensibilizantes/farmacologia , Resveratrol/farmacologia , Sesquiterpenos/farmacologia , Triterpenos/farmacologia , Vitamina D/farmacologia , Vitanolídeos/farmacologia
4.
Nutrients ; 13(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34684666

RESUMO

Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disease in females of reproductive age and is characterized by multifactorial unhealthy conditions related to hormonal unbalance and also to dysmetabolism and inflammation. Recently, increasing evidence has shown that natural plant-based products may play a role in PCOS management. The aim of this one-group pretest-post-test explanatory study was to evaluate, in normal-overweight PCOS women with normal menses, the effectiveness of berberine on: Insulin resistance (IR) by Homeostasis Model Assessment (HOMA); Inflammation by C-Reactive Protein (CRP), Tumor Necrosis Factor α (TNF-α); Lipid metabolism; Sex hormone profile and symptoms correlated to hyperandrogenism, such as acne, by Global Acne Grading System (GAGS) and Cardiff Acne Disability Index (CADI); Body composition by DXA. Finally, adverse effects were assessed by liver and kidney functions and creatine phosphokinase (CPK). All these parameters were collected at baseline and 60 days after supplementation with a new bioavailable and safe berberine formulation. Twelve females (aged 26.6 ± 4.9, BMI 25.3 ± 3.6) were supplied for 60 days with two tablets/day (550 mg/table) of the bioavailable berberine. Results showed a statistically significant decrease in HOMA, CRP, TNF-α, Triglycerides, testosterone, Body Mass Index (BMI), Visceral Adipose Tissue (VAT), fat mass, GAGS and CADI scores, and a statistically significant increase in sex hormone-binding globulin (SHBG). Liver and kidney functions and CPK are not statistically significantly different. Therefore, berberine can represent a safe novel dietary supplement, helpful in treatment strategy for PCOS.


Assuntos
Berberina/farmacologia , Hormônios/metabolismo , Insulina/metabolismo , Fosfolipídeos/farmacologia , Síndrome do Ovário Policístico/metabolismo , Adulto , Composição Corporal/efeitos dos fármacos , Determinação de Ponto Final , Feminino , Humanos , Inflamação/patologia , Resistência à Insulina , Modelos Lineares , Lipídeos/sangue , Síndrome do Ovário Policístico/sangue
5.
Molecules ; 26(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34684678

RESUMO

BACKGROUND: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. METHODS: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. RESULTS: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. CONCLUSIONS: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.


Assuntos
Nefropatias/tratamento farmacológico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Antioxidantes/farmacologia , Berberina/farmacologia , Beta vulgaris , Betalaínas/farmacologia , Produtos Biológicos/farmacologia , Catequina/farmacologia , Curcumina/farmacologia , Dissulfetos/farmacologia , Flavonoides/farmacologia , Humanos , Isotiocianatos/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Romã (Fruta) , Resveratrol/farmacologia , Ácidos Sulfínicos/farmacologia , Sulfóxidos/farmacologia , Xantofilas/farmacologia
6.
J Integr Med ; 19(6): 545-554, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34686466

RESUMO

OBJECTIVE: To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms. METHODS: A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. RESULTS: FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation. CONCLUSION: BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.


Assuntos
Berberina , Hepatopatia Gordurosa não Alcoólica , Berberina/farmacologia , Colesterol , Proteína Forkhead Box O1/genética , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Sirtuína 1/genética , Proteínas de Ligação a Elemento Regulador de Esterol
7.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4201-4207, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467733

RESUMO

The present study aims to investigate the effects of the main components(aesculin, berberine hydrochloride, and anemoside B4) in the butyl alcohol extract of Baitouweng Decoction(BAEB) on the chemotaxis of neutrophils induced by dimethyl sulfoxide(DMSO). HL60 cells were cultivated in RPMI-1640 complete medium, and transferred into a 6-well plate(2 × 10~5 per mL) with 4 mL in each well, followed by incubation with DMSO at 1.3% for five days. The morphologic changes of cells were observed under an inverted microscope. The CD11 b expression after DMSO induction was analyzed by flow cytometry. The effects of aesculin, berberine hydrochloride, and anemoside B4 on the cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The effects of the main components on the production and polarization of F-actin protein were also examined by flow cytometry and laser confocal microscopy. PI3 K/Akt signaling pathway was checked by Western blot. As revealed by the results, neutrophil-like HL60 cells were observed after DMSO induction. The CD11 b expression in these cells increased significantly as indicated by the flow cytometry. Additionally, 100 µg·mL~(-1) aesculin, 8 µg·mL~(-1) berberine hydrochloride, and 80 µg·mL~(-1) anemoside B4 were potent in inhibiting the migration of neutrophils and reducing F-actin expression. Berberine hydrochloride was verified to be capable of diminishing phosphorylated PI3 K/Akt protein expression. The findings indicate that aesculin, anemoside B4, and especially berberine hydrochloride in the BAEB can inhibit the chemotaxis of neutrophils, which is possibly achieved by the inhibition of F-actin and PI3 K/Akt signaling pathway.


Assuntos
Berberina , Medicamentos de Ervas Chinesas , 1-Butanol , Berberina/farmacologia , Quimiotaxia , Medicamentos de Ervas Chinesas/farmacologia , Neutrófilos
8.
Nat Commun ; 12(1): 5503, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535644

RESUMO

Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease -4.8% vs. -2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes.


Assuntos
Berberina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estudo de Prova de Conceito , Adiposidade/efeitos dos fármacos , Adulto , Idoso , Berberina/efeitos adversos , Berberina/farmacologia , Feminino , Hemoglobina A Glicada/análise , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade
9.
Shanghai Kou Qiang Yi Xue ; 30(3): 258-262, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476441

RESUMO

PURPOSE: This study aimed at exploring the effect of berberine (C20H18NO4) on osteogenic differentiation of rat adipose-derived stem cells(ADSCs) and clarifying the related mechanism. METHODS: ADSCs were subjected to 5, 10, 20 µmol/L berberine culture solution. The untreated ADSCs were set as the control group. Cell proliferation activity was determined by MTT method. Alkaline phosphatase (ALP) staining, semi-quantitative assay and alizarin red staining (ARS) were applied to analyze the effect of berberine on osteogenic differentiation of ADSCs. The phosphorylation level of c-Jun amino terminal kinase (JNK) protein was tested by Western blot. Runx2, OCN were tested by Western blot before and after application of JNK pathway inhibitor SP600125. SPSS 22.0 software package was used for statistical analysis. RESULTS: There was no significant difference on cell proliferation activity of ADSCs treated with 5, 10 and 20 µmol/L berberine at 1, 3 and 7 day(P>0.05). ALP staining and ARS staining in groups treated by berberine were significantly darker than those of the control group, and ALP protein secretion in the experimental group was significantly up-regulated (P<0.05). The phosphorylation level of JNK was increased after treated with 10 µmol/L berberine culture medium. The expression of osteogenic related proteins Runx2 and OCN was up-regulated in the experimental group. After inhibition of JNK signaling pathway, the expression of Runx2 and OCN was down-regulated. CONCLUSIONS: Berberine has no effect on cell proliferation of ADSCs, and can up-regulate osteogenic differentiation of ADSCs through activation of JNK signaling pathway.


Assuntos
Berberina , Osteogênese , Animais , Berberina/farmacologia , Diferenciação Celular , Células Cultivadas , Sistema de Sinalização das MAP Quinases , Ratos , Células-Tronco
10.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576028

RESUMO

Lung cancer is one of the most common cancers and the leading cause of death in humans worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases and is often diagnosed at a late stage. Among patients with NSCLC, 50% die within 1 year after diagnosis. Even with clinical intervention, the 5-year survival rate is only approximately 20%. Therefore, the development of an advanced therapeutic strategy or novel agent is urgently required for treating NSCLC. Berberine exerts therapeutic activity toward NSCLC; therefore, its activity as an antitumor agent needs to be explored further. In this study, three terpenylated-bromide derivatives of berberrubine were synthesized and their anti-NSCLC activities were evaluated. Each derivative had higher anti-NSCLCs activity than berberrubine and berberine. Among them, 9-O-gernylberberrubine bromide (B4) and 9-O-farnesylberberrubine bromide (B5) showed greater growth inhibition, cell-cycle regulation, in vitro tumorigenesis suppression, and tumor migration reduction. In addition, some degree of apoptosis and autophagic flux blocking was noted in the cells under B4 and B5 treatments. Our study demonstrates that the berberrubine derivatives, B4 and B5, exhibit impressive anti-NSCLC activities and have potential for use as chemotherapeutic agents against NSCLC.


Assuntos
Berberina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células A549 , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Berberina/síntese química , Berberina/química , Berberina/farmacologia , Brometos/química , Carcinogênese/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Terpenos/síntese química , Terpenos/farmacologia
11.
J Food Biochem ; 45(10): e13936, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34523148

RESUMO

Berberine is one of the most important quinoline alkaloids, which has shown numerous pharmacological activities. There are pieces of evidence that berberine serves as a promising substance for treating Alzheimer's disease (AD). Recently, numerous studies on animal models have shown the neuroprotective role of berberine. AD is a complex disease having multiple pathological factors. Berberine restrains the deposition of amyloid plaques and neurofibrillary tangles. Substantial studies have demonstrated that berberine may also exhibit the protective effect against the risk factors associated with AD. This review illustrates the role of berberine in neuroinflammation, oxidative stress and its activity against acetylcholinesterase enzyme. It also focuses on the bioavailability and safety of berberine in AD. However, more investigations are required to explore the bioavailability and safety assessment of berberine and its new perspectives in limiting the AD-related pathogenesis and risk factors. PRACTICAL APPLICATIONS: Current therapeutic measures only provide symptomatic relief against AD by slowing memory loss, resolving thinking problems and behavioral issues. In recent past years, many biological actions and potential therapeutic applications have been observed by berberine particularly in neurological diseases. Berberine has been investigated by various researchers for its activity against AD. This review demonstrates a variety of mechanisms by which berberine imparts its neuroprotective roles and provides the possible mechanism of action of berberine by which it prevents the formation of neurofibrillary tangles and disaggregation of amyloid beta plaques in AD. It also focuses that berberine limits the neuroinflammation and oxidative stress in AD. Pre-clinical aspects of berberine against AD are also discussed. Eventually, a prospect is formulated that berberine might be a therapeutically significant agent for treating and preventing AD.


Assuntos
Doença de Alzheimer , Berberina , Acetilcolinesterase , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Estresse Oxidativo
12.
Life Sci ; 284: 119928, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480937

RESUMO

AIMS: Berberine is effective for type 2 diabetes mellitus (T2DM), but has limited use in clinic. This study aims to evaluate the effect of berberine combined with stachyose on glycolipid metabolism and gut microbiota and to explore the underlying mechanisms in diabetic rats. MAIN METHODS: Zucker diabetic fatty (ZDF) rats were orally administered berberine, stachyose and berberine combined with stachyose once daily for 69 days. The oral glucose tolerance and levels of blood glucose, insulin, triglyceride and total cholesterol were determined. The gut microbial profile, colonic miRNA and gene expression were assayed using Illumina sequencing. The quantitative polymerase chain reaction was used to verify the expression of differentially expressed miRNAs and genes. KEY FINDINGS: Repeated treatments with berberine alone and combined with stachyose significantly reduced the blood glucose, improved the impaired glucose tolerance, and increased the abundance of beneficial Akkermansiaceae, decreased that of pathogenic Enterobacteriaceae in ZDF rats. Furthermore, combined treatment remarkably decreased the abundances of Desulfovibrionaceae and Proteobacteria in comparison to berberine. Combined treatment evidently decreased the expression of intestinal early growth response protein 1 (Egr1) and heparin-binding EGF-like growth factor (Hbegf), and significantly increased the expression of miR-10a-5p, but berberine alone not. SIGNIFICANCE: Berberine combined with stachyose significantly improved glucose metabolism and reshaped gut microbiota in ZDF rats, especially decreased the abundance of pathogenic Desulfovibrionaceae and Proteobacteria compared to berberine alone, providing a novel strategy for treating T2DM. The underlying mechanisms may be associated with regulating the expression of intestinal Egr1, Hbegf and miR-10a-5p, but remains further elucidation.


Assuntos
Berberina/farmacologia , Colo/metabolismo , Diabetes Mellitus Experimental/genética , Microbioma Gastrointestinal , Regulação da Expressão Gênica , Glucose/metabolismo , MicroRNAs/genética , Oligossacarídeos/farmacologia , Animais , Colo/efeitos dos fármacos , Colo/microbiologia , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , MicroRNAs/metabolismo , Análise de Componente Principal , Ratos Zucker , Reprodutibilidade dos Testes , Transcriptoma/genética
13.
Gynecol Obstet Invest ; 86(4): 388-397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515131

RESUMO

OBJECTIVES: The aim of this study was to investigate the effects of berberine on polycystic ovary syndrome (PCOS) with insulin resistance (IR). DESIGN: This study performed 16S rRNA sequencing and metabolomic analysis on dehydroepiandrosterone (DHEA)-induced PCOS rats treated with berberine, focusing on the improvement of PCOS-IR by modifying gut microbiota and metabolism. METHODS: Forty-two female Sprague Dawley rats were randomly divided into 4 experimental groups of 8 rats each (PCOS + HFD, PCOS + HFD + BBR, NCD + PCOS, and NCD + PCOS + BBR groups). Homeostasis model assessment of insulin resistance (HOMA-IR) index-related indicators and hormone level in serum were analyzed. 16S rRNA sequencing and metabolomic analysis were performed on DHEA-induced PCOS rats treated with berberine. In addition, the differential microbiotas and metabolites were screened. Also, enrichment analysis was carried out on the differential metabolites. Finally, we constructed a correlation network to analyze the correlation between differential microbiotas and metabolites. RESULTS: Firmicutes and Bacteroidetes were changed at the phylum level, and Romboutsia, Bacteroides, and Clostridium_sensu_stricto_1 were changed at the genus level after berberine treatment. In addition, a total of 26 differential operational taxonomic units and 3 metabolites (glutamine, unsaturated acids [CH = CH], and glucose) between 2 groups were obtained. Moreover, these metabolites were mainly involved in type 2 diabetes mellitus, 2-component system, and ABC transporter Kyoto Encyclopedia of Genes and Genomes pathways. And, 3 microbiotas (Lachnospiraceae_NC2004_group, Flavonifractor, and Parasutterella) were regulated by glucose and glutamine. LIMITATIONS: The sample size involved in this study is relatively small. In addition, relevant experiments need to be performed to verify the obtained results from this study, and in-depth functional studies are needed. CONCLUSIONS: Berberine is effective in improving the pathological condition in PCOS by regulating the gut microbiotas and metabolites. This study will provide evidence for therapeutic efforts to treat PCOS-IR using berberine.


Assuntos
Berberina , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistência à Insulina , Síndrome do Ovário Policístico , Animais , Berberina/farmacologia , Desidroepiandrosterona , Feminino , Humanos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley
14.
Nat Commun ; 12(1): 5616, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556670

RESUMO

Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet ß-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.


Assuntos
Berberina/farmacologia , Canais de Potássio Éter-A-Go-Go/metabolismo , Hiperglicemia/metabolismo , Secreção de Insulina/efeitos dos fármacos , Secretagogos/farmacologia , Adolescente , Adulto , Animais , Linhagem Celular Tumoral , Estudos Cross-Over , Dieta Hiperlipídica/efeitos adversos , Canais de Potássio Éter-A-Go-Go/genética , Células HEK293 , Humanos , Hiperglicemia/etiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Adulto Jovem
15.
Phytomedicine ; 91: 153654, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333328

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a clinical syndrome with reproductive and endocrine disorders. Berberine is a monomer from Chinese herbs such as Coptis chinensis, whose effect on improving ovulation and endometrial receptivity of PCOS is uncertain. PURPOSE: To evaluate the effect of berberine on improving PCOS and explore the mechanism. METHODS: The rat model of PCOS was induced by intraperitoneal injection of testosterone propionate. Then they was divided into model (Mod) group, low-dose of berberine (BL) group, high-dose of berberine (BH) group and metformin (Met) group as well as a control (Con) group was established. Ovary morphology, hormone level, glucolipid metabolism were measured. UID-mRNA-seq of ovary tissue was conducted to seek the mechanism of berberine on improving ovulation. Three biomarkers of endometrial receptivity were also examined in endometrium by immunohistochemistry. RESULTS: The number of cystic follicles was increased while the number of corpus luteum was decreased in the rats of Mod group. These changes could be reversed by high-dose of berberine intervention. Berberine could also decrease the levels of serum luteinizing hormone (LH) and total cholesterol (TC) in PCOS rats. Meanwhile, berberine improved the impairment of abnormal oral glucose tolerance without affecting fasting insulin level and Homeostasis model assessment-insulin resistance (HOMA-IR). Luteinizing hormone/ choriogonadotropin receptor (LHCGR) and cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1) were focused via RNA-seq of ovary. Protein expression in ovary and mRNA expression in granulosa cell of LHCGR and CYP19A1 were decreased in Mod group and rescued by the intervention of berberine. A decrease of endometrial thickness and an increase of integrin αvß3 and lysophosphatidic acid receptor 3 (LPAR3) protein expression were observed in Mod group, which could be also reversed by berberbine. CONCLUSIONS: Berberine could improve ovulation in PCOS and the mechanism might be associated with up-regulating LHCGR and CYP19A1. Berberine could also improve endometrial receptivity through down-regualting αvß3 and LPAR3.


Assuntos
Berberina , Ovulação/efeitos dos fármacos , Síndrome do Ovário Policístico , Animais , Berberina/farmacologia , Endométrio/efeitos dos fármacos , Feminino , Metformina , Síndrome do Ovário Policístico/tratamento farmacológico , Ratos
16.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443321

RESUMO

Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR's pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Quinase I-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Linhagem Celular , Quimiocina CCL2/metabolismo , Ciclo-Oxigenase 2/metabolismo , Humanos , Interleucina-8/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
17.
Phytomedicine ; 91: 153678, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34385092

RESUMO

BACKGROUND: Demethyleneberberine (DMB) is a natural active component of medicinal plant Cortex phellodendri chinensis with favorable bioactivity. However, the role of DMB in suppressing non-small cell lung cancer (NSCLC) remains unknown. PURPOSE: In this study, we aimed to examine the effect and underlying mechanism of DMB in suppressing NSCLC. METHODS: CCK8 assay and colony formation assay were utilized to assess the efficiency of DMB on the viability and colony formation capacity of NSCLC cells. Flow cytometry and ß-Galactosidase Staining Kit were utilized to determine the efficiency of DMB on the cell cycle and cellular senescence of NSCLC cells. RT-qPCR and Western blot were used to detect the effect of DMB on cell cycle and cellular senescence related gene and protein expression of NSCLC cells. In vivo tumor model was established to evaluate the anti NSCLC effect of DMB. In addition, RNA-seq analysis was performed to detect the differential gene expression after DMB treatments. RESULTS: In this study, we revealed that DMB exhibits efficient inhibitory effect on NSCLC cell proliferation and tumor xenografts growth in vivo. We also demonstrated that DMB could inhibit cell migration by suppressing epithelial-mesenchymal transition (EMT) and trigger cell cycle arrest by down-regulating the expression of cell cycle related genes in NSCLC cells. In addition, DMB treatment efficiently induces cellular senescence of NSCLC cells. From the RNA-seq analysis, we found that DMB accelerates senescence through suppressing HIF-1α expression, which was further elucidated by overexpressing HIF-1α in NSCLC to reduce the inhibitory effect of DMB. Furthermore, we also revealed that DMB decreases the expression of c-Myc, an up-stream protein of HIF-1α. CONCLUSIONS: Taken together, we first report that DMB inhibits NSCLC progress through inducing cell cycle arrest and triggering cellular senescence by downregulating c-Myc/HIF-1α pathway.


Assuntos
Berberina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Berberina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Senescência Celular/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Life Sci ; 284: 119884, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389401

RESUMO

BACKGROUND: Liver injury results in excessive extracellular matrix (ECM) deposition in the liver, which is mainly produced by hepatic stellate cells (HSC). Alpha-smooth muscle actin (α-SMA) and liver enzymes are the two hallmarks of liver injury. Previously, it has been confirmed that berberine (BBR) attenuates liver injury. This study aimed to investigate the protective effect of Poly Lactic-co-Glycolic Acid (PLGA) encapsulated BBR against liver injury. METHODS: Nanoprecipitation, encapsulation, and physio-chemical characterization of BBR-PLGA nanoparticles (BBR-PLGA-NP) have been done. The protective effects of BBR-PLGA-NPs and BBR against carbon tetrachloride (CCl4)-treated Wistar rats were investigated. The serum levels of alanine aminotransferase and aspartate transaminase were measured, and the expression level of α-SMA was quantified by qRT-PCR. To evaluate the liver changes, morphological and histological staining was done. RESULTS: BBR-PLGA-NPs markedly reduced serum ALT and AST in rats treated with CCl4. Although the expression level of α-SMA was downregulated in the CCl4-injected rats that were treated with BBR, α-SMA expression in this group was still remarkably higher than the control group. α-SMA mRNA was significantly under-expressed (p < 0.05) by BBR-PLGA-NPs and the hepatic histology revealed BBR-PLGA-NPs made further improvements than free BBR. CONCLUSION: The use of nanoparticle to encapsulate BBR is a worthy approach to enhance the curative effect of BBR against liver injuries, which donate a safe and effective drug delivery strategy to treat liver injuries.


Assuntos
Actinas/genética , Berberina/farmacologia , Regulação da Expressão Gênica , Fígado/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Actinas/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
19.
Sci Rep ; 11(1): 15770, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349203

RESUMO

Berberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.


Assuntos
Berberina/farmacologia , Cardiolipinas/metabolismo , Diabetes Gestacional/etiologia , Dieta Hiperlipídica/efeitos adversos , Cardiopatias/etiologia , Cardiopatias/prevenção & controle , Troca Materno-Fetal/fisiologia , Mitocôndrias Cardíacas/metabolismo , Miocárdio/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Berberina/administração & dosagem , Transporte de Elétrons/efeitos dos fármacos , Ácidos Graxos/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Oxirredução/efeitos dos fármacos , Gravidez
20.
ACS Appl Mater Interfaces ; 13(27): 32295-32306, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34196538

RESUMO

Synthetic fungicides have been widely used to protect crops from fungal diseases. However, excessive use of synthetic fungicides leads to the generation of fungicide resistance in fungal pathogens. Recently, smart cargo delivery systems have been introduced for the construction of a pesticide delivery nanoplatform, benefiting from their controlled release performance. Herein, a fungal pathogen microenvironment-responsive supramolecular fungicide nanoplatform has been designed and constructed, using quaternary ammonium salt (Q)-modified mesoporous silica nanoparticles (MSN-Q NPs) as nanocarriers loaded with berberine hydrochloride (BH) and carboxylatopillar[5]arene (CP[5]A) as nanogates to form BH-loaded CP[5]A@MSN-Q NPs for effective inhibition of Botrytis cinerea. CP[5]A as nanogates can endow the fungicide nanoplatform with pH stimuli-responsive release features for the control of fungicide release. The loaded BH, as a natural plant fungicide, provides an ecofriendly alternative to synthetic fungicides for controlling B. cinerea. Interestingly, we use oxalic acid (OA) secreted by B. cinerea as a trigger so that BH can be released from the fungicide nanoplatform on demand under pathogen microenvironments for controlling B. cinerea. The experimental results indicate that the fabricated fungicide nanoplatform could effectively inhibit the mycelial growth and spore germination, providing a new way for the management of B. cinerea in actual application.


Assuntos
Portadores de Fármacos/química , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Nanopartículas/química , Dióxido de Silício/química , Berberina/química , Berberina/farmacologia , Botrytis/efeitos dos fármacos , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Porosidade , Compostos de Amônio Quaternário/química
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