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1.
Biosci Biotechnol Biochem ; 84(1): 63-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31462179

RESUMO

A natural isoquinoline alkaloid, berberine, has been known to exhibit anti-tumor activity in various cancer cells via inducing cell cycle arrest. However, it has not been investigated whether berberine and its analogs inhibit the growth of rhabdomyosarcoma (RMS), which is the most frequent soft tissue tumor in children. The present study examined the anti-tumor effects of berberine and palmatine on expansions of three human embryonal RMS cell lines; ERMS1, KYM1, and RD. Intracellular incorporation of berberine was relatively higher than that of palmatine in every RMS cell line. Berberine significantly inhibited the cell cycle of all RMS cells at G1 phase. On the other hand, palmatine only suppressed the growth of RD cells. Both of berberine and palmatine strongly inhibited the growth of tumorsphere of RD cells in three-dimensional culture. These results indicate that berberine derivatives have the potential of anti-tumor drugs for RMS therapy.Abbreviations: ARMS: alveolar rhabdomyosarcoma; ERMS: embryonal rhabdomyosarcoma; RMS: rhabdomyosarcoma.


Assuntos
Antineoplásicos/farmacologia , Alcaloides de Berberina/farmacologia , Berberina/farmacologia , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/patologia , Antineoplásicos/química , Berberina/análogos & derivados , Berberina/química , Alcaloides de Berberina/química , Linhagem Celular Tumoral , Ciclina D1/genética , Inibidor de Quinase Dependente de Ciclina p57/genética , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/genética , Conformação Molecular , Simulação de Acoplamento Molecular , Phellodendron/química , Rabdomiossarcoma Alveolar/metabolismo , Rabdomiossarcoma Embrionário/metabolismo
2.
Pestic Biochem Physiol ; 159: 51-58, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400784

RESUMO

Isoquinoline alkaloids possess broad pharmacological activities. In this study, the antifungal activity of twelve isoquinoline alkaloids, including berberine (1), jatrorrhizine (2), coptisine (3), corydaline (4), tetrahydroberberine (5), chelidonine (6), dihydrosanguinarine (7), chelerythrine (8), sanguinarine (9), palmatine (10), tetrahydropalmatine (11) and columbamine (12) were evaluated against eight plant pathogenic fungi in vitro. All the tested compounds showed varying degrees of inhibition against the eight tested plant fungi. Among them, sanguinarine exhibited high antifungal activity (EC50 ranging from 6.96-59.36 µg/mL). It displayed the best inhibitory activity against Magnaporthe oryzae (EC50 = 6.96 µg/mL), compared with azoxystrobin (EC50 = 12.04 µg/mL), and significantly suppressed spore germination of M. oryzae with the inhibition rate reaching 100% (50 µg/mL). The optical microscopy and scanning electron microscopy observations revealed that after treating M. oryzae mycelia with sanguinarine at 10 µg/mL, the mycelia appeared curved, collapsed and the cell membrane integrity was eventually damaged. Furthermore, the reactive oxygen species production, mitochondrial membrane potential and nuclear morphometry of mycelia had been changed, and the membrane function and cell proliferation of mycelia were destroyed. These results will enrich our insights into action mechanisms of antifungal activity of sanguinarine against M. oryzae.


Assuntos
Alcaloides/farmacologia , Antifúngicos/farmacologia , Benzofenantridinas/farmacologia , Isoquinolinas/farmacologia , Berberina/análogos & derivados , Berberina/farmacologia , Alcaloides de Berberina/farmacologia , Magnaporthe/metabolismo , Magnaporthe/patogenicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Espécies Reativas de Oxigênio/metabolismo
3.
Curr Protein Pept Sci ; 20(10): 996-1003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389311

RESUMO

Abstract:Throughout the last decade, extensive efforts have been devoted to developing a percutaneous catheter ablation and implantable cardioverter-defibrillator technique for patients suffering from ventricular arrhythmia. Antiarrhythmic drug efficacy for preventing arrhythmias remains disappointing because of adverse cardiovascular effects. Allocryptopine is an isoquinoline alkaloid widely present in medicinal herbs. Studies have indicated that allocryptopine exhibits potential anti-arrhythmic actions in various animal models. The potential therapeutic benefit of allocryptopine in arrhythmia diseases is addressed in this study, focusing on multiple ion channel targets and reduced repolarization dispersion. The limitations of allocryptopine research are clear given a lack of parameters regarding toxicology and pharmacokinetics and clinical efficacy in patients with ventricular arrhythmias. Much remains to be revealed about the properties of allocryptopine.


Assuntos
Antiarrítmicos , Arritmias Cardíacas/tratamento farmacológico , Alcaloides de Berberina , Plantas Medicinais/química , Traqueófitas/química , Animais , Antiarrítmicos/química , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/uso terapêutico , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
4.
Psychopharmacology (Berl) ; 236(11): 3169-3182, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31172225

RESUMO

RATIONALE: Levo-tetrahydropalmatine (l-THP), an active ingredient of Corydalis yanhusuo, has been reported to be a partial agonist for dopamine D1 receptors (D1R) and an antagonist for D2R. Although it has been safely used clinically in China for decades as an analgesic with sedative/hypnotic properties, there are few studies that address the mechanisms by which l-THP exerts its beneficial effects in chronic pain-induced sleep disturbance. OBJECTIVES: To investigate the effects and mechanisms of l-THP on sleep disturbance in a neuropathic pain-like condition. METHODS: A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSNL) was employed. The antinociceptive and hypnotic effects of l-THP were evaluated by measurement of mechanical allodynia, thermal hyperalgesia, and electroencephalogram (EEG) recordings in PSNL mice. Pharmacological approaches and c-Fos expression were used to clarify the mechanisms of l-THP. RESULTS: Intraperitoneal injection of l-THP at 5 and 10 mg/kg not only significantly increased the mechanical threshold by 134.4% and 174.8%, and prolonged the thermal latency by 49.4% and 69.2%, but also increased non-rapid eye movement sleep by 17.5% and 29.6%, and decreased sleep fragmentation in PSNL mice, compared with the vehicle control. Moreover, the antinociceptive effect of l-THP was prevented by D1R antagonist SCH23390 or D2R agonist quinpirole; meanwhile, the hypnotic effect of l-THP was blocked by quinpirole rather than by SCH23390. Immunohistochemistry demonstrated that l-THP inhibited c-Fos overexpression induced by PSNL in the cingulate cortex and the periaqueductal gray. CONCLUSIONS: These findings indicated that l-THP exerted analgesic effects by agonism D1R and antagonism D2R, and the antagonism of D2R mediated the hypnotic effect of l-THP in PSNL mice.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Alcaloides de Berberina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Neuralgia/tratamento farmacológico , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Analgésicos não Entorpecentes/farmacologia , Animais , Alcaloides de Berberina/farmacologia , Modelos Animais de Doenças , Antagonistas dos Receptores de Dopamina D2/farmacologia , Antagonistas dos Receptores de Dopamina D2/uso terapêutico , Eletroencefalografia/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/fisiopatologia , Receptores de Dopamina D1/agonistas
5.
Biochimie ; 162: 176-184, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31051209

RESUMO

Palmatine is a natural isoquinoline alkaloid and has been widely used in pharmaceutical field. The purpose of this review is to provide the latest and comprehensive information on the pharmacology, toxicity and pharmacokinetics of palmatine in the past, to explore the therapeutic potential of this compound and look for ways to reduce toxicity. Information on palmatine was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library and Europe PMC using a combination of keywords including "pharmacology", "toxicology", "pharmacokinetics". All studies of this genus were included in this review until March 2019. Palmatine has a wide spectrum of pharmacological effects, including anti-cancer, anti-oxidation, anti-inflammatory, neuroprotection, anti-bacterial, anti-viral and regulating blood lipids. However, palmatine has obvious DNA toxicity, and has a complex effect on metabolic enzymes in the liver. Pharmacokinetic studies have demonstrated that glucuronidation and sulfation are the main metabolic pathways of palmatine. Palmatine can be used in many diseases. Future research directions include: how the concentration of palmatine affects pharmacological effects and toxicity; the mechanism of synergy between palmatine and other protoberberine alkaloid; Structural modification of palmatine is one of the key methods to enhance pharmacological activity and reduce activity.


Assuntos
Bactérias/efeitos dos fármacos , Alcaloides de Berberina , Medicamentos de Ervas Chinesas , Extratos Vegetais , Animais , Alcaloides de Berberina/farmacocinética , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/toxicidade , Células Cultivadas , Bases de Dados Bibliográficas , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Coelhos , Ratos
6.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 69-75, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078155

RESUMO

Objective of this study was to investigate the sedative and hypnotic effects of palmatine and to observe whether its mechanism is related to 5-hydroxytryptamine (5-HT) and GABA. The sedative and hypnotic effects of palmatine on mice were observed with mouse autonomic activity test, direct sleep test, pentobarbital sodium in suprathreshold and subthreshold dose sleep test. The content of GABA and 5-HT in brain homogenate was determined by ELISA  method. Mouse brain specimens were observed by immunohistochemistry for 5-HT expression in the nucleus of mouse brain. Palmatine could reduce spontaneous activities of mice, prolong the sleep time of mice induced by pentobarbital sodium in suprathreshold dose and shorten the sleep latency.  And it could increase the number of mice falling asleep induced by pentobarbital sodium in subthreshold dose and the incidence of falling asleep, but with no direct sleep effect. In addition, it enhanced the 5-HT content in brain, but had no effect on GABA content, and had no toxicity to PC12 cells. Palmatine plays a significant role in sedation and hypnosis, which may be associated with the increase of intra-cerebral 5-HT.


Assuntos
Alcaloides de Berberina/farmacologia , Hipnóticos e Sedativos/farmacologia , Serotonina/metabolismo , Animais , Alcaloides de Berberina/química , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Células PC12 , Pentobarbital/administração & dosagem , Ratos , Receptores de GABA/metabolismo , Padrões de Referência , Sono/efeitos dos fármacos , Fatores de Tempo , Ácido gama-Aminobutírico/metabolismo
7.
J BUON ; 24(2): 701-708, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128026

RESUMO

PURPOSE: Το evaluate the effect of L-Tetrahydropalmatine (L-THP) on the sensitivity of a cisplatin resistant ovarian cancer (OC) cell line. As miR-93 is reported to be overexpressed in OC and cisplatin resistance, we also evaluated its pathway in OC. METHODS: The levels of miR-93 were evaluated using RT-PCR and Luciferase assay was performed to confirm the target of miR-93. The extent of apoptosis was evaluated by Annexin V and propidium iodide (PI) staining, whereas Hoechst 33258 staining was done for identifying the number of apoptotic cells. RESULTS: The cisplatin-resistant A2780/DDP cell line showed lower survival rate compared to control when incubated with L-THP along with cisplatin. L-THP caused G0/G1 cell cycle arrest and increased the sensitivity to cisplatin. Furthermore, we found that the levels of miR-93 in cisplatin-resistant cells were highly expressed compared to parental cells. L-THP suppressed the expression of miR-93 and increased the levels of PTEN, a crucial tumor suppressor in OC. It was further observed that the cells transfected with PTEN siRNA showed increased survival compared with the control group and this phenomenon could be reversed by the AKT inhibitor Triciribine. The A2780 cells treated with PTEN siRNA showed similar survival rate to the cells with miR-93 overexpression. CONCLUSION: The findings of this study suggested L-THP increased the sensitivity of ovarian cancer cells to cisplatin via modulating miR-93/PTEN/AKT pathway in A2780/DDP ovarian cancer cell line.


Assuntos
Alcaloides de Berberina/farmacologia , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , RNA Interferente Pequeno/genética , Ribonucleosídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transfecção
8.
Photochem Photobiol Sci ; 18(6): 1596-1605, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31099374

RESUMO

Oral squamous cell carcinoma (OSCC) is a common malignant tumor, accounting for about 7% of all malignant tumors. Palmatine hydrochloride (PaH) is the alkaloid constituent of Fibraurea tinctoria Lour. The present study aims to investigate the antitumor effect of photodynamic therapy (PDT) with PaH (PaH-PDT) on human OSCC cell lines both in vitro and in vivo. The results indicate that PaH-PDT exhibited a potent phototoxic effect in cell proliferation and produced cell apoptosis. PaH-PDT increased the percentage of cells in the G0/G1 phase and decreased the CDK2 and Cyclin E1 protein level. In addition, PaH-PDT markedly increased the generation of intracellular ROS, which can be suppressed using the ROS scavenger N-acetylcysteine (NAC). Furthermore, PaH-PDT increased the expression of p53 protein in vitro and in vivo. In vivo experiments revealed that the PaH-PDT resulted in an effective inhibition of tumor growth and prolonged the survival time of tumor-bearing mice. Moreover, no obvious signs of side effects or a drop in body weight was observed. These results suggested that PaH was a promising sensitizer that can be combined with light to produce significant anti-tumor effects in oral squamous cell carcinoma via enhanced ROS production and up-regulated expression of p53.


Assuntos
Antineoplásicos/farmacologia , Alcaloides de Berberina/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Alcaloides de Berberina/química , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Lasers , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
9.
Nucleic Acids Res ; 47(13): e73, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30949695

RESUMO

Regions of genomic instability are not random and often co-localize with DNA sequences that can adopt alternative DNA structures (i.e. non-B DNA, such as H-DNA). Non-B DNA-forming sequences are highly enriched at translocation breakpoints in human cancer genomes, representing an endogenous source of genetic instability. However, a further understanding of the mechanisms involved in non-B DNA-induced genetic instability is needed. Small molecules that can modulate the formation/stability of non-B DNA structures, and therefore the subsequent mutagenic outcome, represent valuable tools to study DNA structure-induced genetic instability. To this end, we have developed a tunable Förster resonance energy transfer (FRET)-based assay to detect triplex/H-DNA-destabilizing and -stabilizing ligands. The assay was designed by incorporating a fluorophore-quencher pair in a naturally-occurring H-DNA-forming sequence from a chromosomal breakpoint hotspot in the human c-MYC oncogene. By tuning triplex stability via buffer composition, the assay functions as a dual-reporter that can identify stabilizers and destabilizers, simultaneously. The assay principle was demonstrated using known triplex stabilizers, BePI and coralyne, and a complementary oligonucleotide to mimic a destabilizer, MCRa2. The potential of the assay was validated in a 384-well plate with 320 custom-assembled compounds. The discovery of novel triplex stabilizers/destabilizers may allow the regulation of genetic instability in human genomes.


Assuntos
Alcaloides de Berberina/farmacologia , Pontos de Quebra do Cromossomo , DNA/efeitos dos fármacos , Transferência Ressonante de Energia de Fluorescência/métodos , Genes myc , Instabilidade Genômica/efeitos dos fármacos , Indóis/farmacologia , Conformação de Ácido Nucleico/efeitos dos fármacos , Piridinas/farmacologia , Alcanossulfonatos/análise , Compostos Azo/análise , Tampões (Química) , Dicroísmo Circular , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Corantes Fluorescentes/análise , Genes myc/efeitos dos fármacos , Genoma Humano , Humanos , Ligantes , Oligodesoxirribonucleotídeos/química
10.
Toxins (Basel) ; 11(4)2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027283

RESUMO

Ovarian cancer ranks amongst the deadliest cancers in the gynaecological category of cancers. This research work aims to evaluate in vitro anti-ovarian cancer activities and identify phytochemical constituents of a rarely explored plant species-Rutidea parviflora DC. The aqueous and organic extracts of the plant were evaluated for cytotoxicity using sulforhodamine B assay in four ovarian cancer cell lines and an immortalized human ovarian epithelial (HOE) cell line. The bioactive compounds were isolated and characterized by gas/liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. Caspase 3/7 activity assay, western blotting and flow cytometry were carried out to assess apoptotic effects of active compounds. The extracts/fractions of R. parviflora showed promising anti-ovarian cancer activities in ovarian cancer cell lines. A principal cytotoxic alkaloid was identified as palmatine whose IC50 was determined as 5.5-7.9 µM. Palmatine was relatively selective towards cancer cells as it was less cytotoxic toward HOE cells, also demonstrating interestingly absence of cross-resistance in cisplatin-resistant A2780 cells. Palmatine further induced apoptosis by increasing caspase 3/7 activity, poly-ADP-ribose polymerase cleavage, and annexin V and propidium iodide staining in OVCAR-4 cancer cells. Our studies warranted further investigation of palmatine and R. parviflora extracts in preclinical models of ovarian cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Alcaloides de Berberina/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Rubiaceae , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Casca de Planta/química , Extratos Vegetais/química
11.
Phytother Res ; 33(6): 1689-1696, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30932278

RESUMO

The tumor suppressor p53 plays essential roles in cellular protection mechanisms against a variety of stress stimuli and its activation induces apoptosis or autophagy in certain cancer cells. Here, we identified protopine, an isoquinoline alkaloid isolated from Nandina domestica, as an activator of the p53 pathway from cell-based natural compound screening based on p53-responsive transcription. Protopine increased the p53-mediated transcriptional activity and promoted p53 phosphorylation at the Ser15 residue, resulting in stabilization of p53 protein. Moreover, protopine up-regulated the expression of p21WAF1/CIP1 and BAX, downstream genes of p53, and inhibited the proliferation of HCT116 colon cancer cells. Apoptosis was elicited by protopine as indicated by caspase-3/7 activation, poly ADP ribose polymerase cleavage, and increased population of Annexin V-FITC-positive cells. Furthermore, protopine induced the formation of microtubule-associated protein 1 light chain 3 (LC3) puncta and LC3-II turnover, typical biochemical markers of autophagy, in HCT116 cells. Our findings suggest that protopine exerts its antiproliferative activity by stimulating the p53 pathway and may have potential as a chemopreventive agent for human colon cancer.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Benzofenantridinas/isolamento & purificação , Benzofenantridinas/uso terapêutico , Alcaloides de Berberina/isolamento & purificação , Alcaloides de Berberina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Ranunculales/química , Apoptose/fisiologia , Autofagia/fisiologia , Benzofenantridinas/farmacologia , Berberidaceae/química , Berberidaceae/classificação , Alcaloides de Berberina/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Relação Dose-Resposta a Droga , Células HCT116 , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estabilidade Proteica/efeitos dos fármacos , Ranunculales/classificação , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
12.
J Photochem Photobiol B ; 194: 140-148, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30954873

RESUMO

Previously, we reported that coralyne and UVA combination sensitized a wide range of human carcinoma cells regardless of their p53 status. The coralyne induced photosensitization of cancer cells may be clinically attractive, as mutation in the p53 gene is prevalent in many types of tumors. Coralyne mediated photosensitization of cancer cells is attributable to its ability to cause extensive DNA single strand breaks (SSB). However, the precise mechanism of coralyne induced DNA photo-damage is not yet known. The present study was aimed to understand the hitherto unknown mechanism of the coralyne-induced DNA photo-cleavage process. To this end, we compared the DNA photo-nicking properties of berberine, jatrorrhizine and coralyne, and deciphered involvement of the photochemical processes in the photo-nuclease action of coralyne using absorption and electron spin resonance spectroscopy, high performance liquid chromatography and mass spectroscopy (MS) techniques in conjunction with relevant in vitro studies with plasmid DNA. In association with UVA, coralyne, but not berberine and jatrorrhizine induced significant nicking of plasmid DNA via an O2-independent photo-chemical process. The Job's plot of our spectrophotometric data suggested that one coralyne molecule remains intercalated with two DNA base pairs (i. e., 1:2) and starts forming aggregates beyond this molar ratio. The DNA photo-nicking by the combination of coralyne and UVA (designated as CUVA) was primarily caused by the coralyne aggregates without any significant contribution from the DNA-intercalated coralyne monomer.


Assuntos
Alcaloides de Berberina/farmacologia , Clivagem do DNA/efeitos dos fármacos , Clivagem do DNA/efeitos da radiação , Berberina/análogos & derivados , Berberina/farmacologia , Luz
13.
Fitoterapia ; 134: 210-220, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30836124

RESUMO

Hyperglycemia is a common endocrine system disease, which seriously affects people's health with a increasing morbidity in recent years. Rhizoma Coptidis (RC), one of the most commonly used traditional Chinese medicines, has been applied to treat diabetes in clinic for thousands of years. Since scientists demonstrated that alkaloids from RC owned the amazing anti-hyperglycemia activities 30 years ago, these compounds have been widely used for the treatment of diabetes and hyperglycemia with unconspicuous toxicities and side effects. With the help of molecular biology, immunology and other techniques, the mechanisms about anti-hyperglycemia effect of RC alkaloids have been extensively discussed. Numerous studies showed that RC alkaloids balanced the glucose homeostasis not only by widely recognizing insulin resistance pathways, but also by promoting insulin secretion, regulating intestinal hormones, ameliorating gut microbiota structures and many other ways. In this review, we combine the latest advances and systematically summarize the mechanisms of RC alkaloids in treating hyperglycemia and diabetic nephropathy to provide a deeper understanding of these natural alkaloids. In addition, the important role of gut microbiota associated with the glucose metabolism is also reviewed.


Assuntos
Alcaloides/farmacologia , Coptis/química , Hipoglicemiantes/farmacologia , Animais , Alcaloides de Berberina/farmacologia , Diabetes Mellitus/tratamento farmacológico , Microbioma Gastrointestinal , Glucose/metabolismo , Humanos , Hiperglicemia/tratamento farmacológico , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Rizoma/química
14.
Parasitol Res ; 118(1): 335-345, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30470927

RESUMO

Berberine chloride, a plant-derived isoquinoline alkaloid, has been demonstrated to have leishmanicidal activity, which is mediated by generation of a redox imbalance and depolarization of the mitochondrial membrane, resulting in a caspase-independent apoptotic-like cell death. However, its impact on mitochondrial function remains to be delineated and is the focus of this study. In UR6 promastigotes, berberine chloride demonstrated a dose-dependent increase in generation of reactive oxygen species and mitochondrial superoxide, depolarization of the mitochondrial membrane potential, a dose-dependent inhibition of mitochondrial complexes I-III and II-III, along with a substantial depletion of ATP, collectively suggesting inhibition of parasite mitochondria. Accordingly, the oxidative stress induced by berberine chloride resulting in an apoptotic-like cell death in Leishmania can be exploited as a potent chemotherapeutic strategy, mitochondria being a prime contributor.


Assuntos
Antiprotozoários/farmacologia , Alcaloides de Berberina/farmacologia , Leishmania/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Leishmania/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
15.
Int J Biol Macromol ; 121: 127-134, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30290263

RESUMO

Using bioinformatics analysis, we found some mature human miRNAs containing G-rich sequences with four G-tracts that had a high probability of forming G-quadruplex structures. Here, we chose G-rich miR-1587 as a model to characterize the function and regulation of miRNAs. Using electrospray ionization mass spectrometry, magnetic resonance imaging, circular dichroism spectrometry, we had confirmed that miR-1587 folded into a stable parallel G-quadruplex structure. By microarray, Q-RT-PCR and 3'UTR luciferase assay, TAGLN, an early marker of smooth muscle differentiation and tumor suppressor, was identified as a target gene of miR-1587, thus providing a direct target to study miR-1587 functions. We identified three aspects of miR-1587 regulation: 1) KCl induced miR-1587 G-quadruplex formation, reducing the interaction between miR-1587 and the target gene, and inhibiting miR-1587 function; 2) pseudopalmatine ligand further inhibited miR-1587 binding to TAGLN mRNA, which disrupted its function and increased the TAGLN expression; 3) the addition of TMPyP4 ligand interfered G-quadruplex formation, and significantly enhanced miR-1587 regulation of TAGLN expression. This study has revealed the possibility of using the G-quadruplex structure as a strategy to regulate miR-1587 function, showing potential for the development of up- and downregulation of mature G-rich microRNA function by modulating its G-quadruplex and using small molecules.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Quadruplex G , MicroRNAs/química , MicroRNAs/genética , Bibliotecas de Moléculas Pequenas/farmacologia , Regulação para Cima/efeitos dos fármacos , Alcaloides de Berberina/farmacologia , Células HeLa , Humanos , Cloreto de Potássio/farmacologia , Transcriptoma/efeitos dos fármacos
16.
Life Sci ; 218: 197-204, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30582951

RESUMO

Hepatocellular carcinoma (HCC) as primary liver cancer in adults is the most common cause led to internal cirrhosis responsible for patients' death, which resulted in nearly a million deaths worldwide on both males and females in the developing and developed countries. Unfortunately, up to date, there are no highly effective treatment of medicine on HCC as lack of comprehensive cellular and molecular mechanism. According to the sources of human ancient history of medicine, traditional medicine could provide unique treatment to discontinue the challenging HCC. In this study, we inspected the effect of Columbamine (Col; C20H21NO5), an alkaloid isolated from calumba, on HCC utilizing three HCC cell-lines i.e. SMMC7721, HepG2 and Hep3B. Our data collected from these cell-lines exhibit strong Col suppression on the cell growth accompanying the dosage-dependent suppression, and we further confirmed the suppression on the tumor-growth in animal model. Rational of the Col suppression presents cellular mechanism by limiting the proliferation and colony formation of the cells marked with decreased expression of PCNA. Meanwhile decreases of migration indicated with increasing expression of E-cadherin and decreasing expression of N-cadherin, and of invasion labelled with decreasing expressions of MMP2 and MMP9, are accompanying the Col suppression along with the Col promoted apoptosis of the tumor cells. This programmed cell death marketed with cleaved Caspase 3 plus PAPR proteins, up-regulation of BAD and down-regulation of BCL2 is linked the Col suppression to unique calcium-related pathways. Our results unveiled that the Columbamine suppression on HCC based on the traditional medicine are clearly associated with PI3K/AKT, p38 and ERK1/2 MAPKs signaling pathways and guide further research orientation for developing the Col medicine against hepatocellular carcinoma.


Assuntos
Alcaloides de Berberina/farmacologia , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Med Sci Monit ; 24: 6564-6572, 2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-30226834

RESUMO

BACKGROUND Hyperlipidemia is a major cause of atherosclerotic cardiovascular disease. Tetrahydropalmatine (THP) can exhibit hepatoprotective, anti-arrhythmic, and anti-inflammatory activities. The mechanism of THP on the hyperlipidemia remains unknown; therefore, the present study explored the role of THP in hyperlipidemia. MATERIAL AND METHODS We established an animal model of hyperlipidemia by high-fat diet (HFD) feeding. Blood samples were obtained for determination of serum cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), pro-inflammatory cytokines, and CYP7A1 expression. Histology was performed and inflammation was detected in the liver using hematoxylin-eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA and protein levels of TLR4 and TRAF-6 were determined by quantitative real-time PCR (qPCR) and Western blot, respectively. RESULTS THP suppressed hepatic lipid accumulation and reduced serum levels of TC, TG, LDL-c, and HDL-c in HFD-fed golden hamsters. THP increased cholesterol 7 a-hydroxylase (CYP7A1) expression and prevented inflammation by the limited reduction in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions in serum and liver. THP slightly increased the ratio of the body/liver weight. THP inhibited the mRNA and protein levels of Toll-like receptor 4 (TLR4) and TNF-receptor associated factor-6 (TRAF-6). CONCLUSIONS These results suggest that THP attenuates hyperlipidemia by multiple effects, including hepatoprotective and anti-inflammatory effects. Moreover, THP also suppressed the expressions of TLR4 and TRAF-6 in golden hamsters.


Assuntos
Alcaloides de Berberina/farmacologia , Hiperlipidemias/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Colesterol/sangue , Colesterol 7-alfa-Hidroxilase/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cricetinae/metabolismo , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado/metabolismo , Masculino , Mesocricetus/metabolismo , Triglicerídeos/sangue
18.
J Comput Aided Mol Des ; 32(9): 917-928, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30171419

RESUMO

The protein lysine methyltransferase G9a, which controls gene expression by epigenetic regulation of H3K9 methylation, is related to various human diseases, including cancer, drug addiction, and mental retardation. In recent years, genetic, biological, and physiological evidence has established G9a inhibitors as potential chemotherapeutic agents for cancer treatment. In this study, we identified protoberberine alkaloid pseudodehydrocorydaline (CT13) as a novel G9a inhibitor, by structure-based virtual screening of in-house library containing natural product compounds. The activity of CT13 was determined by biophysical analyses involving MALDI-TOF mass spectrometry and western blot analysis. CT13 showed selective inhibitory activity against G9a and suppressed the level of H3K9me2 in MCF7 human breast cancer cells. Molecular docking analysis suggested the binding mode of CT13 which occupies the binding site of histone H3 substrate. CT13 provides a novel scaffold for further development of analogous synthetic G9a inhibitors.


Assuntos
Alcaloides de Berberina/química , Histona Metiltransferases/antagonistas & inibidores , Alcaloides de Berberina/farmacologia , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , Histonas/química , Humanos , Células MCF-7 , Metilação , Simulação de Acoplamento Molecular , Ligação Proteica , Bibliotecas de Moléculas Pequenas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Relação Estrutura-Atividade
19.
Pharmacol Res ; 137: 34-46, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30243842

RESUMO

Inflammatory bowel disease (IBD), majorly include Crohn's disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days. Pal (50 and 100 mg kg-1) and the positive drug Sulfasalazine (SASP, 200 mg kg-1) were orally administered for 7 days. Disease activity index (DAI) was evaluated on day 8, and colonic tissues were collected for biochemistry analysis. The fecal microbiota was characterized by high-throughput Illumina MiSeq sequencing. And plasma metabolic changes were detected by UPLC-MS. Our results showed that Pal treatment significantly reduced DAI scores and ameliorated colonic injury in mice with DSS-induced colitis. Mucosal integrity was improved and cell apoptosis was inhibited. Moreover, gut microbiota analysis showed that mice received Pal-treatment have higher relative abundance of Bacteroidetes and Firmicutes, but reduced amount of Proteobacteria. Moreover, Pal not only suppressed tryptophan catabolism in plasma, but also decreased the protein expression of indoleamine 2,3-dioxygenase 1 (IDO-1, the rate-limiting enzyme of tryptophan catabolism) in colon tissue. This is consolidated by molecular docking, which suggested that Pal is a potent IDO-1 inhibitor. Taken together, our findings demonstrate that Pal ameliorated DSS-induced colitis by mitigating colonic injury, preventing gut microbiota dysbiosis, and regulating tryptophan catabolism, which indicated that Pal has great therapeutic potential for colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Alcaloides de Berberina/farmacologia , Alcaloides de Berberina/uso terapêutico , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Triptofano/metabolismo , Animais , Colite/metabolismo , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos BALB C , Mucinas/genética , Proteínas de Junções Íntimas/genética
20.
Biomed Res Int ; 2018: 8308640, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854796

RESUMO

This study aimed to investigate the effects of different microbial growth media on the laboratory assessment of antimicrobial activity of natural polyphenolic compounds. The inhibition of the tea polyphenol EGCG on growth of selected oral microorganisms was evaluated in complex media and a protein-free chemically defined medium (CDM). Other antimicrobial agents (polyphenolic grape seed extract, plant alkaloid berberine, methyl salicylate, and chlorhexidine gluconate) were also tested in the study. The presence of proteins and their effects on the antimicrobial activity of EGCG were investigated by the addition of BSA to the CDM. The MICs of EGCG against test oral microorganisms were 4 to 64 times higher in complex media than in CDM. The polyphenolic grape seed extract exhibited similar discrepancies. However, the MICs of the nonpolyphenolic compounds (berberine, methyl salicylate, and chlorhexidine) were not significantly different between the two growth media. The MIC of EGCG against S. mutans UA159 in CDM with added BSA was 16 times higher than that in CDM alone. Therefore, nonproteinaceous CDM should be used to avoid interference of proteins with the active ingredients when testing the antimicrobial activity of plant-derived polyphenolic compounds against microorganisms. This will also minimize the discrepancies noted in results obtained by different investigators.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Clorexidina/análogos & derivados , Clorexidina/química , Clorexidina/farmacologia , Meios de Cultura , Extrato de Sementes de Uva/química , Extrato de Sementes de Uva/farmacologia , Testes de Sensibilidade Microbiana/métodos , Salicilatos/química , Salicilatos/farmacologia , Chá/química
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