RESUMO
Chinese cordyceps, also known as Dong-Chong-Xia-Cao, is widely recognized as a famous precious tonic herb, and used as traditional Chinese medicine for centuries. It is mainly used for regulating the immune system and improving functions of the lung and kidney, with anti-tumor, anti-inflammatory, and anti-diabetic activities. Due to its rarity and preciousness, a few chemical components are isolated and identified. Moreover, most of them are common chemical components and widely distributed in other natural resources, such as nucleosides, sterols, fatty acids, sugar alcohols, and peptides. Therefore, a large number of active substances of Chinese cordyceps is still unclear. During our search for chemical constituents of Chinese cordyceps, a new thiazole alkaloid, cordythiazole A (1), was isolated and identified. Its structure was elucidated by comprehensive spectroscopic analysis and single-crystal X-ray diffraction analysis. This is the first report of the presence of thiazole alkaloid in Chinese cordyceps, which adds a new class of metabolite of Chinese cordyceps. Furthermore, a putative biosynthesis pathway of cordythiazole A was proposed based on possible biogenic precursor, genes, and literatures. In addition, it showed α-glucosidase inhibitory activity with potency close to that of acarbose. The discovery of cordythiazole A with α-glucosidase inhibitory activity adds a new class of potential anti-diabetes ingredient in Chinese cordyceps.
Assuntos
Alcaloides , Antineoplásicos , Cordyceps , Cordyceps/química , alfa-Glucosidases , Alcaloides/farmacologiaRESUMO
Based on the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway, this study investigated the effect of medicated serum of Sparganii Rhizoma(SR) and Curcumae Rhizoma(CR) on the proliferation, apoptosis, migration, and secretion of inflammatory factors of ectopic endometrial stromal cells(ESCs). Specifically, human ESCs were primary-cultured. The effect of different concentration(5%, 10%, 20%) of SR-, CR-, and SR-CR combination-medicated serum, and AG490 solution(50 µmol·L~(-1)) on the proliferation of ESCs was detected by methyl thiazolyl tetrazolium(MTT) assay, and the optimal dose was selected accordingly for further experiment. The cells were classified into normal serum(NS) group, SR group(10%), CR group(10%), combination(CM) group(10%), and AG490 group. The apoptosis level of ESCs was detected by flow cytometry, and the migration ability was examined by wound healing assay. The secretion of interleukin(IL)-1ß, IL-6, and tumor necrosis factor(TNF)-α was determined by enzyme-linked immunosorbent assay(ELISA). The protein levels of cysteinyl aspartate specific protei-nase-3(caspase-3), B-cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) and the levels of phosphorylated(p)-JAK2 and p-STAT3 were detected by Western blot. The results showed that the viability of ESCs cells was lowered in the administration groups compared with the blank serum group(P<0.01), especially the 10% drug-medicated serum, which was selected for further experiment. The 10% SR-medicated serum, 10% CR-medicated serum, and 10% CM-medicated serum could increase the apoptosis rate(P<0.01), up-regulate the protein expression of caspase-3 and Bax in cells(P<0.05 or P<0.01), down-regulate the expression of Bcl-2(P<0.01), decrease the cell migration rate(P<0.05 or P<0.01), and reduce the secretion levels of IL-1ß, IL-6, and TNF-α(P<0.05 or P<0.01), and levels of p-JAK2 and p-STAT3(P<0.05 or P<0.01). Compared with the SR and CR groups, CM group showed low cell viability(P<0.01), high protein expression of caspase-3 and Bax(P<0.05 or P<0.01), and low protein expression of Bcl-2 and p-JAK2(P<0.05). After incubation with CM, the apoptosis rate was higher(P<0.05) and the migration rate was lower(P<0.01) than that of the CR group. The p-STAT3 protein level of CM group was lower than that of the RS group(P<0.05). The mechanism of SR, CR, and the combination underlying the improvement of endometriosis may be that they blocked JAK2/STAT3 signaling pathway, inhibited ESC proliferation, promoted apoptosis, weakened cell migration, and reduced the secretion of inflammatory factors. The effect of the combination was better than that of RS alone and CR alone.
Assuntos
Interleucina-6 , Janus Quinase 2 , Feminino , Humanos , Caspase 3 , Proteína X Associada a bcl-2 , Interleucina-6/genética , Apoptose , Transdução de Sinais , Proliferação de Células , Fator de Transcrição STAT3/genéticaRESUMO
Neuroinflammation has been suggested to be involved in the pathogenesis of postoperative cognitive dysfunction (POCD). Electroacupuncture (EA) is an irreplaceable method in traditional Chinese medicine that is used for treating neurodegenerative diseases in clinical and experimental studies. The aim of this study was to examine whether EA improves cognitive dysfunction caused by surgery and to investigate the pathological mechanism of TLR2 and TLR4 in the hippocampus of aged rats. A rat model of POCD was established and treated with EA or minocycline. Both EA- and minocycline-treated rats performed significantly better than untreated operated rats in spatial memory tasks of the Morris water maze (MWM) test, spending comparatively greater amounts of time in the target zone during the probe test. Additionally, decreased levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α, and HMGB1) and decreased TLR2 and TLR4 protein expression in the hippocampus of EA- and minocycline-treated rats were detected. Our data suggested that EA treatment alleviated the cognition performance deficit and neuroinflammation in aged rats following surgery, which may be mediated by inhibiting the expression of hippocampal neuroinflammatory cytokines through the microglia/TLR2/4 pathway.
RESUMO
OBJECTIVE: To observe the clinical effect of Ziyin Huoxue Granule (ZHG) combined glucocorticoids and antibiotics in treatment of radiation pneumonitis. METHODS: Totally 70 radiation pneumonitis patients were assigned to the treatment group and the control group according to random digit table, 35 in each group. All patients received glucocorticoids and antibiotics. Patients in the treatment group additionally took ZHG, one dose per day for 4 successive weeks. Watters clinical-radiologic-physiologic (CRP) score, Karnofsky Performance Status Scale (KPS) , and acute radiation injury classification [set by Radiation Therapy Oncology Group (RTOG)] were observed in the two groups before and after treatment. The application time for antibiotics and glucocorticoids was compared between the two groups. RESULTS: All patients completed this trial, and nobody dropped out or died. There was no statistical difference in Watters-CRP scores, KPS, or RTOG between the two groups before treatment (P > 0.05). Compared with before treatment in the same group, RTOG classification was obviously improved in the two groups (P < 0.05). Compared with the control group, Watters-CRP scores decreased, KPS increased, the application time for antibiotics and glucocorticoids was reduced (P < 0.05). The efficacy of RTOG classification was better in the treatment group than in the control group, but with no statistical difference between the two groups (P > 0.05). CONCLUSION: ZHG combined glucocorticoids and antibiotics was superior in treating radiation pneumonitis to using glucocorticoids or antibiotics alone in elevating Watters-CRP scores, shortening the application time for glucocorticoids and antibiotics, and improving patients' physical conditions.
Assuntos
Antibacterianos/uso terapêutico , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Glucocorticoides/uso terapêutico , Pneumonite por Radiação/tratamento farmacológico , Humanos , Avaliação de Estado de KarnofskyRESUMO
To investigate the effect of Tanreqing injection on immune activity of peripheral blood lymphocytes of patients with lung cancer. The peripheral blood lymphocytes of patients with lung cancer and healthy persons were separated by the density gradient centrifugation method for subsequent experiments, with those from healthy persons as the positive control. The effect of Tanreqing injection on stimulating the proliferation of lymphocytes with phytohemagglutinin (PHA) was determined by MTT method. The effect of Tanreqing injection on the lymphocyte secretions of IFN-γ and TNF-α and the subset ratio of lymphocytes cultured separately or with Tanreqing injection of different concentrations were examined by ELISA and flow cytometry (FCM) respectively. In addition, the LDH release assay was used to detect the cytotoxicity of cytotoxic T cells (CTL) and natural killer cells (NK). According to the findings, all of immunological indexes of lymphocytes from patients with lung cancer were weaker than that of healthy persons, but with the obvious increases in proliferation activity and IFN-γ and TNF-α secretions of lymphocytes co-cultured with Tanreqing Injection (P < 0.05). Among lymphocyte subsets co-cultured with Tanreqing Injection, CD3+, CD3+ CD4+ and CD3- CD16 + 56+ cell ratios notably increased, whereas CD4+ CD25+ Treg cell ratio obviously decreased (P < 0.05). In the meantime, Tanreqing injection can markedly promote the cytotoxicities of CTL and NK (P < 0.05). In conclusion, Tanreqing injection shows a significant effect in promoting the immune activity of lymphocytes from patients with lung cancer and their anti-tumor immunity.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Linfócitos T Citotóxicos/imunologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Interferon gama/genética , Interferon gama/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
In this study, we investigate the efficacy of SP (Schisandra polysaccharide) in prevention of radiation-induced immune dysfunction and discussed the underlying mechanisms with a Bal/bc mouse model. The data demonstrated that SP could reverse the decreases in the number of white blood cells and lymphocytes in peripheral blood. In addition, the immunoglobulin G (IgG) and complement C3 in blood serum were all decreased after radiation and SP could restore this radiation disorder. Furthermore, SP could reverse the deregulation of CD3(+)CD4(+) and CD3(+)CD8(+) T cell subsets in peripheral blood and thymus of mice after radiotherapy. We also performed terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and Immunohistochemistry (IHC) to investigate the apoptosis and underlying mechanisms of SP in thymus. Data showed that radiation-induced apoptosis of thymocytes could be reversed by SP through inducing upregulation of Bcl-2 expression and downregulation of Fas and Bax levels. Furthermore, SP has no any side-effects on immunity of normal mice. In conclusion, our results indicated that SP could effectively prevent immune injury during radiotherapy by protecting the immune system. This valuable information should be of assistance in choosing a rational design for therapeutic interventions of prevention immune system damage in the radiation treatment.
Assuntos
Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/efeitos da radiação , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Radiação , Schisandra/química , Animais , Complemento C3 , Regulação da Expressão Gênica/efeitos dos fármacos , Imunoglobulina G/sangue , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/efeitos da radiação , Timócitos/efeitos dos fármacos , Timócitos/efeitos da radiação , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Receptor fas/genética , Receptor fas/metabolismoRESUMO
Suxiao Jiuxin Pill, a compound Chinese traditional medicine with main components of tetramethylpyrazine and borneol, is widely used for antiangina treatment in China but its pharmacological effect on human blood vessels is unknown. We investigated the effect and possible mechanism of SJP in the human internal mammary artery (IMA, n = 78) taken from patients undergoing coronary surgery. SJP caused full relaxation in KCl- (99.4 ± 10.5%, n = 6) and U46619- (99.9 ± 5.6%, n = 6) contracted IMA. Pretreatment of IMA with plasma concentrations of SJP (1 mg/mL), calculated from the plasma concentration of its major component borneol, significantly depressed the maximal contraction to KCl (from 35.8 ± 6.0 mN to 12.6 ± 5.6 mN, P = 0.03) and U46619 (from 19.4 ± 2.9 mN to 5.7 ± 2.4 mN, P = 0.007) while SJP at 10 mg/mL abolished the subsequent contraction. Endothelium denudation and inhibition of eNOS significantly altered the SJP-induced relaxation without changes of eNOS expression. We conclude that SJP has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors in human arteries. The vasorelaxation involves both endothelium-dependent and -independent mechanisms. Thus, the effect of SJP on human arteries demonstrated in this study may prove to be particularly important in vasorelaxing therapy in cardiovascular disease.
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OBJECTIVE: To establish an HPLC method for simultaneous determination of six organic acids in Lonicerae japonicae Flos and Lonicerae Flos in different habitats. METHODS: The chromatographic separation was carried out on a Waters C18 column (4. 6 mm x 250 mm, 5 microm) with gradient elution of acetonitrile and 0.1% phosphoric acid at a flow rate of 1 mL/min. The detection wave-length was 326 nm. RESULTS: The contents of neochlorogenic acid and cryptochlorogenic acid in Lonicerae japonicae Flos in different habitats were very low. The contents of chlorogenic acid in Lonicerae japonicae Flos in Pingyi, Fei County, Fengqiu and Jvlu were significantly higher than that in Shangluo, but the contents of other organic acids were similar. The contents of six kinds of organic acids in Lonicerae Flos in different origins were obviously higher than those in Lonicerae japonicae Flos. CONCLUSION: A simple, accurate and credible method is developed and validated for quality control of six organic acids from Lonicerae japonicae Flos and Lonicerae Flos.
Assuntos
Ácido Clorogênico/análise , Medicamentos de Ervas Chinesas/análise , Flores/química , Lonicera/química , Ácido Quínico/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Flores/crescimento & desenvolvimento , Lonicera/classificação , Lonicera/crescimento & desenvolvimento , Controle de Qualidade , Ácido Quínico/análise , Reprodutibilidade dos TestesRESUMO
The optimal neoadjuvant and adjuvant treatment for gastric cancer remains controversial. We conducted a phase II study using preoperative chemotherapy with modified FOLFOX6 followed by surgical resection and postoperative chemoradiation in patients with gastric carcinoma. Preoperative chemotherapy (two or three cycles) consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2). Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 45 Gy and 5-FU continuous infusion (350 mg/m2/day). The primary end points were feasibility, overall response rate, and R0 resectability rate after preoperative chemotherapy. The secondary end points were tolerability, treatment-associated complications, disease-free survival, and overall survival. Nineteen patients were enrolled in this study. After neoadjuvant treatment, four patients (21.1%) experienced progressive disease, six patients (31.6%) showed partial remission, and nine patients (47.3%) showed stable disease. In 15 patients (78.9%) R0 resectability could be achieved. Eleven of these patients (73.3%) were able to undergo postoperative chemoradiation. Notably, eight (72.7%) of these patients were disease free and alive at median follow-up of 60 months. Chemotherapy associated neutropenia, neutropenic fever, and anastomotic dehiscence were observed. The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.
Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia Adjuvante/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório , Intervalo Livre de Doença , Feminino , Fluoruracila , Humanos , Estimativa de Kaplan-Meier , Leucovorina , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Compostos Organoplatínicos , Neoplasias Gástricas/mortalidadeRESUMO
Cochinchina momordica seeds (CMS) have been widely used due to antitumor activity by Mongolian tribes of China. However, the details of the underlying mechanisms remain unknown. In the present study, we found that an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition of melanoma B16 F1 cells. CMSEE at the concentration of 5-200 µg/ml exhibited strongest anti-proliferative effects on B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanoma B16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, as well as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAP accompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1 cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducing differentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cells through modulating MAPKs activity, which may throw some light on the development of potentially therapeutic strategies for melanoma treatment.
Assuntos
Diferenciação Celular/efeitos dos fármacos , MAP Quinase Quinase 4/metabolismo , Melanoma Experimental/patologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Momordica/química , Fitoterapia , Sementes/química , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Ésteres/química , Citometria de Fluxo , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Camundongos , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais , Células Tumorais CultivadasRESUMO
In situ micro-suction cups were used to collect samples of soil solution with Arundo donax Linn and Typha latifolia from defined segments at rhizosphere in field. The experiment was conducted to elucidate the contribution of iron plaque while wetland plants were used to remove phosphorus. The reddish iron plaque was observed and measured on the surfaces of roots of Arundo donax Linn and Typha latifolia in the field, 20,170.8 mg/kg (fresh weight) for Arundo donax Linn and 7640.3 mg/kg (fresh weight) for Typha latifolia were collected. Olsen-P contents of Arundo donax Linn with iron plaque were 28.85 mg/kg, 46.2% more than that of without, 34.99 mg/kg for Typha latifolia 21.9% more than that of without. The phosphate concentrations in the in situ rhizosphere soil solution of Arundo donax Linn with iron plaque were 0.65 mg/kg, 9.2% more than that of without, 0.56 mg/kg for Typha latifolia, 33.9% more than that of without. The phosphorus contents adsorbed by iron plaque were 81.7% for Arundo donax Linn and 85.7% for Typha latifolia of the wetland plants with iron plaque. Phosphate use efficiency of Arundo donax Linn with iron plaque was 16.5% more than that of without, 31.4% for Typha latifolia. The contents of phosphorus of single plant of the two wetland plants with iron plaque are higher than that of without. Due to adsorb phosphate with iron plaque, the transfer speeds of phosphate from non-rhizosphere to rhizosphere and from soil to soil solution are increasing. The phosphorus contents with iron plaque accumulated at rhizosphere and depleted at rhizosphere without iron plaque of Arundo donax Linn and Typha latifolia.