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1.
Int J Biol Macromol ; 261(Pt 1): 129667, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272401

RESUMO

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal condition characterized by regurgitating stomach contents into the esophagus, causing mucosal damage or erosion. Clinical physical protection treatment mainly relies on the use of floating rafts. Bletilla striata (BS) is widely regarded as the first-choice drug for treating digestive tract injuries in Chinese Medicine. The rapid-floating gel-raft (B-R) was prepared via a one-step swelling method using natural BS polysaccharide and glyceryl monooleate. Panax notoginseng saponins (PNS) were loaded to further prepare P/B-R according to clinical experience. Possessing hydrophobic dense, stratified porous structure and stable rheological properties, an outperforming floating performance of P/B-R was proven compared with Gaviscon® (alginate-antacid formulation) in vitro. In vivo imaging results showed that P/B-R can retain and adhere to the gastric mucosa of rats for up to 90 min, protecting and repairing the mucosa. Besides physical protection in situ, the systemic effects of antioxidant and anti-inflammatory actions for treating GERD were achieved through the intestinal release of PNS. Acid-labile PNS was protected by P/B-R against gastric acid, attaining the desired release and permeability. A significantly effective mucosa injury protective effect of P/B-R was found in ethanol-induced gastric damage model on rats. Moreover, P/B-R exhibits excellent biosafety at the cellular level.


Assuntos
Antiulcerosos , Refluxo Gastroesofágico , Ratos , Animais , Refluxo Gastroesofágico/tratamento farmacológico , Antiácidos
2.
Curr Psychol ; : 1-9, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-37359664

RESUMO

Most people worldwide suffer from resource scarcity in their lives. Perceived scarcity plays an important role in cognitive abilities and decision-making. This study employed the perceived scarcity, self-control, self-efficacy, and delayed gratification scales to explore the relationship among perceived scarcity, self-efficacy, self-control, and delayed gratification as well as the mediating role of self-efficacy and self-control between perceived scarcity and delayed gratification. A cross-sectional survey was conducted via an online survey platform with 1,109 Chinese college students. The results showed that perceived scarcity was negatively correlated with individual self-efficacy, self-control, and delayed gratification, while self-efficacy and self-control played a partial parallel-mediated role between perceived scarcity and delayed gratification. The mediation model accounted for 28% of the variance in delayed gratification. Moreover, the results indicated that perceived scarcity can reduce the delay in gratification through its negative impact on individual self-efficacy and self-control. To some extent, this result explains how perceived scarcity delays gratification from the perspective of motivation and cognition and provides support for further research on the intervention of perceived scarcity's psychological and behavioral consequences.

3.
Drug Dev Res ; 84(2): 262-274, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36658700

RESUMO

Dendrobium nobile Lindl. is registered in the Chinese Pharmacopoeia as a traditional medicine. Phytochemical investigation of the ethanol extract of D. nobile Lindl. stems yielded three alkaloid compounds, including two new compounds dendroxine B (2) and denrine B (3) as well as one known compound dendrobine (1). Here, we identified the structure of these compounds using spectroscopic analyses and compared them with those described in previous studies. Compounds 1-3 were found to show protective effect against amyloid-ß 1-42 (Aß1-42 )-induced neurotoxicity in rat pheochromocytoma (PC12) cells, among which dendrobine exhibited the most significant neuroprotective effect. Hoechst 33342/propidium iodide staining indicated that dendrobine ameliorated Aß1-42 -induced apoptosis. Moreover, quantitative real-time polymerase chain reaction and western blot analysis analysis demonstrated that dendrobine suppressed the activation of cyclin-dependent kinase 5 (CDK5), upregulated Bcl-2 expression, and downregulated Bax, cyto-c, and caspase-3 expression. Molecular docking analysis and surface plasmon resonance assay suggested that dendrobine directly bound to CDK5 protein with a KD value of 2.05 × 10-4 M. In summary, alkaloids are the neuroprotective constituents of D. nobile Lindl., and dendrobine protected PC12 cells against Aß1-42 -induced apoptosis by inhibiting CDK5 activation.


Assuntos
Alcaloides , Dendrobium , Animais , Ratos , Dendrobium/química , Quinase 5 Dependente de Ciclina/farmacologia , Células PC12 , Simulação de Acoplamento Molecular , Alcaloides/farmacologia , Apoptose
4.
Front Oncol ; 12: 857068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936711

RESUMO

Electromagnetic Field (EMF) influences melanoma in various ways. EMF can be classified into extremely low-frequency electromagnetic field, low-frequency magnetic field, static moderate magnetic field, strong electromagnetic field, alternating magnetic field, and magnetic nanoparticles. Each type of EMF influences melanoma development differently, and the detailed influence of each specific type of EMF on melanoma is reviewed. Furthermore, EMF influences melanoma cell polarity and hence affects drug uptake. In this review, the impacts of EMF on the effectiveness of drugs used to treat melanoma are listed according to drug types, with detailed effects according to the types of EMF and specific melanoma cell lines. EMF also impacts clinical therapies of melanoma, including localized magnetic hyperthermia, focalized thermotherapy, proton radiation treatment, nanostructure heating magnetic hyperthermia, radiation therapy, Polycaprolactone-Fe3O4 fiber mat-based bandage, and optune therapy. Above all, EMF has huge potential in melanoma treatment.

5.
Cell Commun Signal ; 19(1): 24, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627137

RESUMO

BACKGROUND: The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis. METHODS: A luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT. RESULTS: Acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity. CONCLUSIONS: The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment. Video Abstract.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/uso terapêutico , Iridoides/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Proteínas Proto-Oncogênicas c-maf/antagonistas & inibidores , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cisteína Endopeptidases/genética , Inibidores de Cisteína Proteinase/farmacologia , Feminino , Humanos , Iridoides/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-maf/genética , Proteínas Proto-Oncogênicas c-maf/metabolismo
6.
Nat Neurosci ; 22(2): 205-217, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30664766

RESUMO

Nuclear receptor corepressor 1 (NCOR1) and NCOR2 (also known as SMRT) regulate gene expression by activating histone deacetylase 3 through their deacetylase activation domain (DAD). We show that mice with DAD knock-in mutations have memory deficits, reduced anxiety levels, and reduced social interactions. Mice with NCOR1 and NORC2 depletion specifically in GABAergic neurons (NS-V mice) recapitulated the memory deficits and had reduced GABAA receptor subunit α2 (GABRA2) expression in lateral hypothalamus GABAergic (LHGABA) neurons. This was associated with LHGABA neuron hyperexcitability and impaired hippocampal long-term potentiation, through a monosynaptic LHGABA to CA3GABA projection. Optogenetic activation of this projection caused memory deficits, whereas targeted manipulation of LHGABA or CA3GABA neuron activity reversed memory deficits in NS-V mice. We describe de novo variants in NCOR1, NCOR2 or HDAC3 in patients with intellectual disability or neurodevelopmental disorders. These findings identify a hypothalamus-hippocampus projection that may link endocrine signals with synaptic plasticity through NCOR-mediated regulation of GABA signaling.


Assuntos
Região CA3 Hipocampal/metabolismo , Neurônios GABAérgicos/metabolismo , Hipotálamo/metabolismo , Transtornos da Memória/genética , Memória/fisiologia , Correpressor 1 de Receptor Nuclear/genética , Correpressor 2 de Receptor Nuclear/genética , Animais , Bases de Dados Factuais , Potenciais Pós-Sinápticos Excitadores/genética , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Transtornos da Memória/metabolismo , Camundongos , Camundongos Transgênicos , Vias Neurais/metabolismo , Plasticidade Neuronal/fisiologia , Correpressor 1 de Receptor Nuclear/metabolismo , Correpressor 2 de Receptor Nuclear/metabolismo , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo
7.
Eur J Cancer ; 100: 1-7, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29933095

RESUMO

BACKGROUND: Collecting duct carcinoma (CDC) is a rare type of renal cancer with a poor prognosis. As there are no standard guidelines for the management of metastatic CDC (mCDC), we evaluated the efficacy and safety of combined therapies of sorafenib, gemcitabine, plus cisplatin in patients with mCDC. MATERIALS AND METHODS: A prospective, multicentre, single-arm, open-label, phase 2 trial (ClinicalTrials.gov identifier NCT01762150) that enrolled 26 mCDC patients with no prior systemic chemotherapy. Patients were treated with sorafenib (400 mg orally, twice daily) combined with chemotherapy (gemcitabine 1000 mg/m2, intravenously for 30-60 min on days 1 and 8, plus cisplatin 25 mg/m2, intravenously on days 1-3, repeated every 28 days for 4 cycles), until disease progression, unacceptable toxicity, or study discontinuation for any other reason. The primary end-points were progression-free survival (PFS) and 6-month PFS rate. RESULTS: The 6-month PFS rate was 65%, and the median PFS was 8.8 months (95% confidence interval [CI]: 6.7-10.9) with a median overall survival of about 12.5 months (95% CI: 9.6-15.4). The objective response rate was 30.8%, and the disease control rate was 84.6%. The treatment was generally well tolerated. Major grade 3/4 toxicities included leucopenia (26.9%), thrombocytopenia (23.1%), anaemia (11.5%) and palmar-plantar erythrodysesthesia (7.7%). CONCLUSIONS: Though the combination of sorafenib and chemotherapy demonstrated a similar outcome as that of the previously reported regimens in patients with mCDC, this combination may be a suitable option for patients who have low Eastern Cooperative Oncology Group performance status or less metastatic sites.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , China , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Sorafenibe/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Gencitabina
8.
Artigo em Inglês | MEDLINE | ID: mdl-28656913

RESUMO

BACKGROUND: Late-onset vitiligo, defined as being aged 50 years and above at the point of clinical onset, remains poorly characterized till now. AIM: This study aims to describe the clinical characteristics and treatment response of patients with late-onset vitiligo. METHODS: We retrospectively reviewed the case records of all patients diagnosed with late-onset vitiligo, from January 1, 2010 to December 31, 2014. Information obtained included patient demographics, characteristics of vitiligo and treatment responses. RESULTS: Of the 3128 patients diagnosed with vitiligo over the 5-year period, 461 (14.7%) had late-onset disease. The study had more females (n = 260, 56.4%) than males, with an average onset age of 59.4 ± 7.4 years. Majority of patients were Chinese (n = 308, 66.8%) and 45 (9.8%) patients had an associated autoimmune disease. Focal vitiligo, defined as the localized presence of depigmented patches, was most common (n = 209, 45.3%). Treatment response was evaluated in 359 patients, of which 216 received monotherapy (topical creams: n = 210, 97.2%; phototherapy: n = 6, 2.8%) and 143 received both modalities. Fifty six (15.6%) patients received oral steroids. Patients who were treated with both topical creams and phototherapy yielded better clinical responses compared to those on monotherapy (P < 0.001) with 56.6% (n = 81) of them achieving good epidermal repigmentation, defined as >50% return of pigmentation compared to baseline (vs. n = 66, 30.6% in the monotherapy group). The choice of phototherapy (targeted, narrowband ultraviolet B or psoralen + ultraviolet A) did not significantly affect clinical response (P = 0.774). LIMITATIONS: This study is limited by its retrospective nature, the nonstandardized documentation resulting in the inability to determine disease progression and associated metabolic comorbidities and also by the gradual loss to follow-up of patients. CONCLUSION: Late-onset vitiligo is not uncommon and tends to be of the focal vitiligo subtype. Nonsegmented vitiligo is more prevalent than segmental vitiligo. Combination therapy with topical medications and phototherapy is superior to monotherapy.


Assuntos
Vitiligo/diagnóstico , Vitiligo/terapia , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/métodos , Fármacos Dermatológicos/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fototerapia/métodos , Estudos Retrospectivos , Esteroides/administração & dosagem , Resultado do Tratamento , Terapia Ultravioleta/métodos
9.
Sci Rep ; 7: 39597, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28054548

RESUMO

The PI3K/mTOR/AKT pathway is activated in most melanomas, but mTOR inhibitors used singly have limited activity against advanced melanomas. The application of nanosecond pulsed electric fields (nsPEFs) is a promising cancer therapy approach. In this study, we evaluated the synergistic anti-tumour efficacy of the mTOR inhibitor everolimus in conjunction with nsPEFs against melanoma. The combined treatment of nsPEFs and everolimus gradually decreased cell growth concurrent with nsPEF intensity. nsPEFs alone or combined with everolimus could promote melanoma cell apoptosis, accompanied with a loss in cellular mitochondrial membrane potential and an increase in Ca2+ levels. In vivo experiments showed that a combination of the mTOR inhibitor everolimus and nsPEFs improved the inhibitory effect, and all skin lesions caused by nsPEFs healed in 1 week without any observed adverse effect. Combination treatment induced caspase-dependent apoptosis through the upregulation of the pro-apoptotic factor Bax and downregulation of the anti-apoptotic factor Bcl-2. Everolimus and nsPEFs synergistically inhibited angiogenesis by decreasing the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and CD34. Our findings indicate that nsPEFs in combination with an mTOR inhibitor can be used as a potential treatment approach for advanced melanoma.


Assuntos
Antineoplásicos/administração & dosagem , Terapia por Estimulação Elétrica/métodos , Everolimo/administração & dosagem , Melanoma/terapia , Neoplasias Cutâneas/terapia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Apoptose , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Humanos , Melanoma/complicações , Melanoma Experimental/complicações , Melanoma Experimental/terapia , Camundongos Endogâmicos BALB C , Neovascularização Patológica/complicações , Fatores de Tempo
10.
Biomed Environ Sci ; 29(8): 574-583, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27660221

RESUMO

OBJECTIVE: To investigate whether recuperating lung decoction (RLD) can modulate the composition of gut microbiota in rats during asthma treatment. METHODS: Fifteen Sprague-Dawley rats were divided randomly and equally into control group, model group, dexamethasone (DEX) group, RLD medium-dose group, and RLD high-dose group. The asthma model was established in all groups, except for the control group. The rats in the DEX and RLD groups were treated orally with DEX and RLD, respectively. The rats in the control and model groups were treated orally with 0.9% saline. The intestinal bacterial communities were compared among groups using 16S rRNA gene amplification and 454 pyrosequencing. RESULTS: The microbial flora differed between the control and model groups, but the flora in the RLD groups was similar to that in the control group. No significant differences were observed between the RLD high-dose and medium-dose groups. RLD treatment resulted in an increase in the level beneficial bacteria in the gut, such as Lactobacillus and Bifidobacterium spp. CONCLUSION: Oral administration of RLD increased the number of intestinal lactic acid-producing bacteria, such as Lactobacillus and Bifidobacterium, in asthma model rats.


Assuntos
Asma/tratamento farmacológico , Bactérias/isolamento & purificação , Medicamentos de Ervas Chinesas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Asma/imunologia , Asma/microbiologia , Bactérias/classificação , Bactérias/genética , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Humanos , Masculino , Plantas Medicinais/química , Ratos , Ratos Sprague-Dawley
11.
J Am Acad Dermatol ; 75(3): 564-571, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27180264

RESUMO

BACKGROUND: Noncultured cellular grafting is a known surgical technique for vitiligo. OBJECTIVE: This study evaluated our center's 12-month repigmentation outcome and its maintenance up to 60 months, factors influencing repigmentation and safety data. METHODS: Clinicoepidemiologic and repigmentation data were reviewed for patients with vitiligo who had undergone noncultured cellular grafting from March 2006 to December 2012 at the National Skin Center, Singapore. RESULTS: All 177 patients who received noncultured cellular grafting during the study period were included. For those with available data, good to excellent repigmentation was present in 83% at 60 months. At 12 months, 88% of patients (n = 52) with segmental vitiligo achieved good to excellent repigmentation compared with 71% (n = 55) with nonsegmental vitiligo (P < .05). More patients on collagen dressings (82%) achieved good to excellent repigmentation compared with those who received hyaluronic acid (63%) (P < .05). Sites of lesions and postgrafting phototherapy did not significantly affect repigmentation outcome. Adverse reactions were uncommon and mild. LIMITATIONS: The study is limited by its retrospective nature, the progressive loss to follow-up of patients, the absence of blinding, and the lack of use of standardized assessment tools. CONCLUSION: Noncultured cellular grafting was successful in allowing more than 80% of patients to achieve good to excellent repigmentation for at least 60 months.


Assuntos
Epiderme/transplante , Pigmentação da Pele/fisiologia , Transplante de Pele/métodos , Vitiligo/cirurgia , Adulto , Bases de Dados Factuais , Células Epidérmicas , Estética , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Singapura , Transplante de Pele/efeitos adversos , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento , Vitiligo/diagnóstico , Cicatrização/fisiologia , Adulto Jovem
13.
J Biomol Screen ; 18(9): 1072-83, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24062352

RESUMO

Transporter proteins are known to play a critical role in affecting the overall absorption, distribution, metabolism, and excretion characteristics of drug candidates. In addition to efflux transporters (P-gp, BCRP, MRP2, etc.) that limit absorption, there has been a renewed interest in influx transporters at the renal (OATs, OCTs) and hepatic (OATPs, BSEP, NTCP, etc.) organ level that can cause significant clinical drug-drug interactions (DDIs). Several of these transporters are also critical for hepatobiliary disposition of bilirubin and bile acid/salts, and their inhibition is directly implicated in hepatic toxicities. Regulatory agencies took action to address transporter-mediated DDI with the goal of ensuring drug safety in the clinic and on the market. To meet regulatory requirements, advanced bioassay technology and automation solutions were implemented for high-throughput transporter screening to provide structure-activity relationship within lead optimization. To enhance capacity, several functional assay formats were miniaturized to 384-well throughput including novel fluorescence-based uptake and efflux inhibition assays using high-content image analysis as well as cell-based radioactive uptake and vesicle-based efflux inhibition assays. This high-throughput capability enabled a paradigm shift from studying transporter-related issues in the development space to identifying and dialing out these concerns early on in discovery for enhanced mechanism-based efficacy while circumventing DDIs and transporter toxicities.


Assuntos
Descoberta de Drogas , Drogas em Investigação/farmacologia , Ensaios de Triagem em Larga Escala , Proteínas de Membrana Transportadoras/metabolismo , Transporte Biológico/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Drogas em Investigação/química , Drogas em Investigação/metabolismo , Corantes Fluorescentes , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas de Membrana Transportadoras/química , Relação Estrutura-Atividade
14.
ACS Appl Mater Interfaces ; 5(16): 7931-6, 2013 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-23844847

RESUMO

In this work, the synthetic alumina nanochannels with bi-, tri-, and tetra-branched geometry structures exhibited ionic current rectifications with nonlinear I-V curves. Such diode performance of the branched alumina nanochannel is mainly dependent on the cooperative asymmetry of the branched structure and the surface-charge distribution on inner walls. By regulating the geometry, electrolyte pH, and solution concentration, the tunable ionic rectification properties are effectively obtained including both the rectification ratios and the rectifying direction that were deduced from the converted ion selectivity. This nanofluidic diode may open up a new opportunity for the application of the complex nanofluidic devices in contrast to previously reported channels to provide molecular analysis, controlled mass transport, drug release, and various logic gate operations.


Assuntos
Óxido de Alumínio/química , Sistemas de Liberação de Medicamentos , Nanoestruturas/química , Humanos , Concentração de Íons de Hidrogênio , Canais Iônicos/química , Íons/química
15.
Chin J Integr Med ; 19(11): 844-52, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23090360

RESUMO

OBJECTIVE: To investigate the preventive effects and possible underlying mechanism of different extracts of Kanggushu () on osteoporosis in ovariectomized rats. METHODS: One hundred and sixtyfive female SD rats were divided into 11 groups: control, sham, model, Xianling Gubao Capsule (), nilestriol, Kanggushu aqueous extract high-, medium-, and low-dose and suet extract high-, medium-, and low-dose groups. The osteoporosis model was made by ovariectomizing the rats. The latter 8 groups were administered intragastricly with Xianling Gubao Capsule, nilestriol, Kanggushu aqueous extract and suet extract for 12 weeks, respectively, while the other 3 groups were administered orally saline. The whole body bone mineral density, bone mineral content, organ coefficient of uterus, serum estradiol and alkaline phosphatase contents, blood calcium, phosphorus, interleukin 6 and bone Gla-protein levels after treatment were monitored. Additionally, three-point bending test of femur, HE staining, and scanning electron microscope were performed to explore the pharmacodynamics and underlying mechanisms. RESULTS: In comparison with ovariectomized rats of model group, Kanggushu aqueous extract high-dose resulted in an increased bone mineral density, bone mineral content and organ coefficient of uterus, improved estradiol level, and improved maximum load and structural stiffness (P<0.05 or P<0.01). Two-dimensional and three-dimensional trabecular structure was also observed under HE staining and scanning electron microscopy, and the number and thickness of trabecular bone in Kanggushu aqueous extract high-dose group was significantly increased compared to the model group, while the lipid droplets in bone marrow cavity were significantly less. However, there were no significant differences in blood calcium, total serum alkaline phosphatase and bone Gla protein among different treatment groups. Overall, the osteoprotective effects of Kanggushu aqueous extract were comparable to those of nilestriol and were significantly more effective than those of Xianling Gubao Capsule. CONCLUSION: The preventive effects of Kanggushu aqueous extract might be partly due to the increased estradiol level, accelerated restoration of bone trabecular reticulate structure, and accordingly increased bone mineral density in osteoporosis rats.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Fosfatase Alcalina/metabolismo , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Cálcio/metabolismo , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fêmur/fisiopatologia , Fêmur/ultraestrutura , Interleucina-6/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Osteocalcina/metabolismo , Osteoporose/sangue , Osteoporose/fisiopatologia , Ovariectomia , Fósforo/metabolismo , Ratos , Ratos Sprague-Dawley , Útero/efeitos dos fármacos , Útero/patologia
16.
J Asian Nat Prod Res ; 15(1): 1-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23231586

RESUMO

Liquid chromatography-photodiode array detector-mass spectrometry-based chemical investigation of the leaves and stems of Premna fulva yielded one new iridoid glycoside (1), one new triterpenoid glycoside (2) along with six known compounds isolated for the first time from the genus. Their structures were established on the basis of extensive spectroscopic data analyses and chemical methods.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Glicosídeos/isolamento & purificação , Glicosídeos Iridoides/isolamento & purificação , Triterpenos/isolamento & purificação , Verbenaceae/química , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos Iridoides/química , Glicosídeos Iridoides/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Caules de Planta/química , Triterpenos/química , Triterpenos/farmacologia
17.
Artigo em Inglês | WPRIM | ID: wpr-293343

RESUMO

<p><b>OBJECTIVE</b>To investigate the preventive effects and possible underlying mechanism of different extracts of Kanggushu () on osteoporosis in ovariectomized rats.</p><p><b>METHODS</b>One hundred and sixtyfive female SD rats were divided into 11 groups: control, sham, model, Xianling Gubao Capsule (), nilestriol, Kanggushu aqueous extract high-, medium-, and low-dose and suet extract high-, medium-, and low-dose groups. The osteoporosis model was made by ovariectomizing the rats. The latter 8 groups were administered intragastricly with Xianling Gubao Capsule, nilestriol, Kanggushu aqueous extract and suet extract for 12 weeks, respectively, while the other 3 groups were administered orally saline. The whole body bone mineral density, bone mineral content, organ coefficient of uterus, serum estradiol and alkaline phosphatase contents, blood calcium, phosphorus, interleukin 6 and bone Gla-protein levels after treatment were monitored. Additionally, three-point bending test of femur, HE staining, and scanning electron microscope were performed to explore the pharmacodynamics and underlying mechanisms.</p><p><b>RESULTS</b>In comparison with ovariectomized rats of model group, Kanggushu aqueous extract high-dose resulted in an increased bone mineral density, bone mineral content and organ coefficient of uterus, improved estradiol level, and improved maximum load and structural stiffness (P<0.05 or P<0.01). Two-dimensional and three-dimensional trabecular structure was also observed under HE staining and scanning electron microscopy, and the number and thickness of trabecular bone in Kanggushu aqueous extract high-dose group was significantly increased compared to the model group, while the lipid droplets in bone marrow cavity were significantly less. However, there were no significant differences in blood calcium, total serum alkaline phosphatase and bone Gla protein among different treatment groups. Overall, the osteoprotective effects of Kanggushu aqueous extract were comparable to those of nilestriol and were significantly more effective than those of Xianling Gubao Capsule.</p><p><b>CONCLUSION</b>The preventive effects of Kanggushu aqueous extract might be partly due to the increased estradiol level, accelerated restoration of bone trabecular reticulate structure, and accordingly increased bone mineral density in osteoporosis rats.</p>


Assuntos
Animais , Feminino , Ratos , Fosfatase Alcalina , Metabolismo , Fenômenos Biomecânicos , Peso Corporal , Densidade Óssea , Cálcio , Metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Estradiol , Sangue , Fêmur , Patologia , Interleucina-6 , Metabolismo , Tamanho do Órgão , Osteocalcina , Metabolismo , Osteoporose , Sangue , Tratamento Farmacológico , Patologia , Ovariectomia , Fósforo , Metabolismo , Ratos Sprague-Dawley , Útero , Patologia
18.
Assay Drug Dev Technol ; 9(5): 522-31, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21561374

RESUMO

Activation of G(i)-coupled G protein-coupled receptor (GPCRs) by their ligands leads to inhibition of adenylyl cyclase (AC) and reduction of cyclic adenosine monophosphate (cAMP) levels in cells. The traditional cAMP assay for G(i)-coupled GPCRs commonly uses forskolin, a nonspecific AC activator, to increase the basal cAMP level in cells to create an assay window for ligand detection. However, there is still a need to develop a nonforskolin-based cAMP assay because of the challenges inherent in titrating the concentration of forskolin to achieve a reliable assay window, along with issues related to the cAMP-independent effects of forskolin. Herein, we describe such an assay by utilizing the endogenous activity of the calcitonin receptor in Chinese hamster ovary (CHO) cells. The calcitonin receptor is a G(s)-coupled GPCR that, when activated by calcitonin, leads to the stimulation of AC and increases cAMP in cells. Thus, we use calcitonin, instead of forskolin, to increase the basal cAMP level in CHO cells to achieve an assay window. We demonstrated that calcitonin peptides robustly increased cAMP accumulation in several CHO cell lines stably expressing well-known G(i)-coupled GPCRs, such as the Dopamine D2 receptor, the Opioid µ receptor, or the Cannabinoid receptor-1. Agonists of these G(i)-coupled GPCRs attenuated calcitonin-induced cAMP production in their receptor stable cell lines. On the other hand, antagonists and/or inverse agonists blocked the effects of their agonists on calcitonin-induced cAMP production. This calcitonin-based cAMP assay has been demonstrated to be sensitive and robust and exhibited acceptable assay windows (signal/noise ratio) and, thus, can be applied to screen for agonists and antagonists/inverse agonists of G(i)-coupled GPCRs in high-throughput screening formats.


Assuntos
Calcitonina/fisiologia , AMP Cíclico/análise , Receptores da Calcitonina/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , 1-Metil-3-Isobutilxantina/farmacologia , Inibidores de Adenilil Ciclases , Animais , Células CHO , Técnicas de Cultura de Células , Colforsina/metabolismo , Colforsina/farmacologia , Cricetinae , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Concentração Inibidora 50 , Ligantes , Terapia de Alvo Molecular , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Ensaio Radioligante , Ratos , Receptores da Calcitonina/agonistas , Receptores da Calcitonina/análise , Receptores da Calcitonina/antagonistas & inibidores , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores de Polipeptídeo Amiloide de Ilhotas Pancreáticas/antagonistas & inibidores , Receptores Opioides mu/análise , Receptores Opioides mu/antagonistas & inibidores , Salmão
19.
Zhongguo Zhen Jiu ; 27(2): 106-8, 2007 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-17370491

RESUMO

OBJECTIVE: To observe the effect of early treatment with acupuncture and motortherapy on developmental quotient (DQ) of cerebral palsy high risk infants. METHODS: Sixty cerebral palsy high risk infants were divided into an acupuncture combined with motortherapy group (treatment group) and a control group, 30 cases in each group. Changes of DQ were investigated by the children mental development scale. RESULTS: The DQ in the treatment group was significantly higher than that in the control group (P < 0.001), with a very significant difference between the two groups in the different grades of DQ (P < 0.005). Incidence of cerebral palsy in the treatment group significantly lower than that in the control group (P < 0.005). CONCLUSION: Acupuncture combined with motortherapy can effectively improve intelligence level and motor function, and reduce the incidence of cerebral palsy for cerebral palsy high risk infants at early stage.


Assuntos
Terapia por Acupuntura , Paralisia Cerebral/terapia , Terapia por Exercício , Paralisia Cerebral/psicologia , Desenvolvimento Infantil , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
20.
Zhongguo Zhong Yao Za Zhi ; 31(13): 1045-7, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-17048595

RESUMO

OBJECTIVE: To understand the effect of illumination, temperature on the germination of the Prunella vulgaris seeds. METHOD: The general germination method. RESULT: Illumination showed no clearly effect on the germination rate of the P. vulgaris seeds under proper temperature condition; However, illumination was the main factor to determine the germination rate of the P. vulgaris seeds when the temperature condition was unsuitable. The germination rate of the P. vulgaris seeds decreased with the time and increased when the marinating time was from 12 to 36 hours. When temperature reached 5-25 9 degrees C, the trend of the germination rate increased at frst and then decreased. CONCLUSION: The optimal germination condition of P. vulgaris seeds is 12 h of marinating time at the temperature of 20 degrees C under illumination.


Assuntos
Germinação , Plantas Medicinais/crescimento & desenvolvimento , Prunella/crescimento & desenvolvimento , Iluminação , Sementes/crescimento & desenvolvimento , Temperatura
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