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1.
J Ethnopharmacol ; 249: 112423, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31765764

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia kansui is a toxic Chinese herbal medicine and exhibits promising treatment to the malignant ascites (MA) in its traditional use. Ingenane-type and jastrophane-type diterpenes are demonstrated to be responsible for the toxicity and efficacy of kansui. Two representative compounds, kansuiphorin C (KPC) and kansuinin A (KA) in each type were proved to effectively reduce the ascites. The biological and toxicological effects are closely associated with the gastrointestinal tract, but the possible mechanism and related metabolic functions of KPC and KA treating MA through modulating the gut microbiota remain unclear. AIM OF THE STUDY: To investigate the possible mechanism and related metabolism of KPC and KA ameliorating malignant ascites through modulating gut microbiota. MATERIALS AND METHODS: MA rats and normal rats were divided into different groups and administrated with KPC, KA, and positive drug, respectively. 16S rDNA gene sequencing and metagenomes analysis combined with the quantification of short-chain fatty acids of feces were performed to reflect the modulation of gut microbiota. Then, the metabolites of KPC and KA in rat feces under the normal and pathological circumstances were detected by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) to explore the in-vivo bacterial biotransformation. RESULTS: KPC and KA were modulatory compounds for gut microbiota. The richness of Lactobacillus and the decreased abundance of Helicobacter involved in the carbohydrate metabolism and amino acid metabolism could be responsible for their prohibitory effects on malignant ascites. KPC exhibited stronger modulation of gut microbiota through making the abundance of Helicobacter about 3.5 times lower than KA. Besides, in-vivo microbial biotransformation of KPC and KA contained oxidation, hydrolysis, dehydration, and methylation to form metabolites of lower polarity. Besides, at the dosage of 10 mg kg-1, the toxicity of both compounds had weaker influences on the gut microbiota of normal rats. CONCLUSION: KPC and KA could ameliorate malignant ascites by modulating gut microbiota mainly containing the increase of Lactobacillus and the decrease of Helicobacter and related carbohydrate and amino acid metabolism, providing a basis for their promising clinical usage.

2.
J Ethnopharmacol ; 245: 112109, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31395303

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata, a traditional herbal medicine, has long been used in Asia and South America for the therapy of hemorrhagic diseases (e.g. hemoptysis, hematemesis, hematuria, epistaxis and uterine bleeding), skin diseases, respiratory disorders, coronary heart disease, hair loss, vitiligo, snake bite and those caused by the deficiency of liver and kidney. AIM OF THE REVIEW: In this review, we highlight relatively comprehensive and up-to-date information of E. prostrata on traditional uses, phytochemistry, pharmacology and toxicity, along with featuring the gaps in current knowledge, aiming to provide references for future research and possible opportunities for well applications of this medicinal plant. MATERIALS AND METHODS: Information on E. prostrata was gathered from scientific databases (Google Scholar, Web of Science, Scifinder, Baidu Scholar, PubMed and CNKI). Information was also obtained from local books, Ph.D. theses and M.Sc. dissertations and Chinese Pharmacopoeia. The plant taxonomy was validated by the database "The Plant List". RESULTS: Various phytochemical classes has been identified and isolated from the plant covering triterpenes, flavonoids, thiopenes, coumestans, steroids and others. Among these, coumestans are reported as the most common ingredients. The isolated crude extracts and individual compounds have been reported to exhibit promising pharmacological properties, such as hepatoprotective, osteoprotective, cytotoxic, hypoglycaemic, anti-inflammatory, anti-microbial, hypolipidemic, promoting hair growth, rejuvenative and neuroprotective effects. CONCLUSIONS: Until now, significant progress has been witnessed in phytochemistry and pharmacology of E. prostrata. Thus, some traditional uses has been well supported and clarified by modern pharmacological studies. Moreover, E. prostrata also showed therapeutic potential in some refractory diseases such as cancer, dementia and diabetes. But, present findings are still insufficient that cannot satisfactorily explain some mechanisms of action. More well-designed studies in vitro especially in vivo are required to establish links between the traditional uses and bioactivities, discover new skeletons and activity molecules, as well as ensure safety before clinical use.

3.
Chin J Integr Med ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31065990

RESUMO

OBJECTIVE: To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice. METHODS: According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01). CONCLUSION: The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.

4.
J Pharm Biomed Anal ; 170: 254-263, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947126

RESUMO

Malignant ascites (MA) is one of the severe complications of gastrointestinal tumors, affecting the patients' survival time and quality of life. Euphorbia kansui is a commonly used toxic Chinese herbal medicine for malignant ascites. Our previous study showed that the biological and toxicological effects of kansui were closely related to the gastrointestinal tract. The ingenane-type and jastrophane-type diterpenoids are both toxic and active components of kansui. The contents of kansuiphorin C (KPC) and kansuinin A (KA) take highest accounts in each type of diterpene. Hence, in this study, the efficacy and toxicity of KPC and KA on normal rats and MA rats were firstly evaluated by serum liver enzymes (ALT and AST), oxidative damage indicators (GSH, SOD, MDA and LDH), inflammatory indexes (TNF-α, IFN-γ and IL-2) and the volume of ascites. Changes in the levels of these indices showed that although the toxicity of KPC on normal rats was stronger than KA, KPC exhibited better efficacy to the malignant ascites with no obvious side effects at the dose of 10 mg·kg-1. Then, accurate and reliable methods for the determination of KPC and KA in the rat feces by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) were established, detected by the multiple reaction monitoring mode. The chromatographic separation was conducted on an XBbridge C18 column (50 mm × 2.1 mm, 2.5 µm) using gradient elution composed of 0.1% formic acid in water and acetonitrile. The flow rate was 0.5 mL·min-1 and column temperature was 30 °C. The method was finally applied to the comparative study on normal and malignant ascites rats given KPC and KA, respectively. Interestingly, the results showed that KPC's accumulative fecal excretion rate (normal, 19.22%±5.36%; model, 15.96%±3.47%) were much higher than that of KA (normal, 2.928%±0.741%; model, 2.835%±0.873%) at the same dose within 48 h. This suggested KPC had higher in-vivo transformations in comparison with KA, providing guidance for the further preclinical research of KPC and KA as promising compounds treating MA.


Assuntos
Ascite/tratamento farmacológico , Diterpenos/química , Fezes/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Euphorbia/química , Masculino , Qualidade de Vida , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
5.
Chin J Nat Med ; 16(11): 846-855, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30502766

RESUMO

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg-1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.


Assuntos
Ceco/cirurgia , Medicamentos de Ervas Chinesas/administração & dosagem , Coração/fisiopatologia , Fenantrenos/administração & dosagem , Punções/efeitos adversos , Salvia miltiorrhiza/química , Sepse/tratamento farmacológico , Animais , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Medicamentos de Ervas Chinesas/química , Feminino , Coração/efeitos dos fármacos , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Ligadura/efeitos adversos , Masculino , Miocárdio/imunologia , Fenantrenos/química , Ratos , Sepse/etiologia , Sepse/imunologia , Sepse/fisiopatologia , Troponina T/genética , Troponina T/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
6.
J Ethnopharmacol ; 219: 257-268, 2018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-29559373

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kansui, the root of Euphorbia kansui S.L.Liou ex S.B.Ho (E.kansui), is a classical traditional Chinese medicine (TCM) with certain toxicity. According to the theory of TCM, kansui fry-baked wtith vinegar (VEK) possesses low toxicity and mild diuretic and purgative efficacy. In clinical practice, it is commonly used for the treatmtablent of ascites and oliguria. The present study aimed to evaluate the toxicity and efficacy of different fractions of VEK and reveal the underlying material basis by employing an animal model of malignant ascites effusion (MAE) in rats. MATERIALS AND METHODSTA: The MAE rats as the model were constructed in SPF male wistar rats by intraperitoneal injection of Walker-256 tumor cells. The MAE rats were used and randomly divided into the control group (normal rats), control groups with different fractions (VEKA, VEKB, VEKC and VEKD), model group (MAE rats), positive control group (model group with furosemide), model groups with different fractions (VEKA, VEKB, VEKC and VEKD). Histopathological observation was used to confirm Walker-256 tumor-bearing organ injuries in rats. For the efficacy evaluation, the ascites and urine volumes, the urinary electrolyte concentrations (Na+, K+ and Cl-) and pH, the ascites levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, IFN-γ and VEGF), PRA, the serum levels of Ang II, ALD and ADH, as well as AQP8 protein expression in the gastrointestinal tract were detected. Furthermore, different levels of indicators were measured in the toxicity evaluation of different fractions both on normal and model rats, including serum liver enzymes (AST and ALT), serum oxidative damage parameters (GSH, MDA, LDH and SOD), expressions of inflammatory parameters (NF-κB, ICAM-1 and E-cadherin) and apoptosis signals (caspase-3, -8, -9, Bcl-2 and Bax) in the liver and gastrointestinal tract. RESULTS: Walker-256 tumor-bearing malignant ascites effusion rats showed obvious hepatic and gastrointestinal injuries by histopathological observation. In the efficacy evaluation, model rats treated with VEKB and VEKC showed significant urine increase (VEKB, P < 0.01; VEKC, P < 0.01) and ascites reduction (VEKB, P < 0.01; VEKC, P < 0.01). These two fractions also balanced the concentrations of Na+, K+ and Cl- in urine (VEKB, all P < 0.05; VEKC, all P < 0.05), remarkably decreased urinary pH (VEKB, P < 0.01; VEKC, P < 0.01), and reduced the ascites levels of IL-2, IL-6, TNF-α, IFN-γ and VEGF (VEKB, all P < 0.01; VEKC, all P < 0.01) in the model rats. Moreover, levels of PRA, the serum Ang II, ALD and ADH of model rats were decreased after treated by VEKB and VEKC (VEKB, all P < 0.05; VEKC, all P < 0.05). Meanwhile, the expression of gastrointestinal AQP8 of the model rats was also enhanced after treated by VEKB and VEKC (VEKB, P < 0.01; VEKC, P < 0.01). In the toxicity evaluation, although VEKB and VEKC caused toxic indexes moved to the worse aspects in normal rats, nearly all of these indicators notably improved in the model rats. Additionally, VEKA showed no effect on the indicators, either in the efficacy evaluation or in the toxicity evaluation. And VEKD could significantly improve some indicators (urine volume, concentration of K+ in urine, serum MDA, AI and caspase-9) in MAE rats. CONCLUSIONS: VEKB and VEKC were demonstrated a significant efficacy in treating malignant ascites effusion, which could reduce hepatic and gastrointestinal damage on the model rats but cause the same damage to the normal. These data embody the traditional Chinese medicine application principle: You Gu Wu Yun. And these results will provide reference for the safer and better clinical utilization of kansui.


Assuntos
Ácido Acético/uso terapêutico , Ascite/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Euphorbia , Raízes de Plantas , Animais , Ascite/metabolismo , Ascite/patologia , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Masculino , Ratos , Ratos Wistar , Resultado do Tratamento
7.
Acta Pharmacol Sin ; 39(2): 230-242, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28816232

RESUMO

Osteoporotic treatments have largely depended on antiresorptive or anabolic drugs; but the former also suppresses new bone formation, and the latter only includes human parathyroid hormone. There is no drug that has a dual effect to inhibit bone resorption and to stimulate bone formation simultaneously. Here, we report a small molecule, a quinoxaline derivative of oleanolic acid (QOA-8a) that plays such dual roles in osteoblasts and osteoclasts in the treatment of osteoporosis. Osteoclast differentiation was induced by incubation of primary mouse bone marrow-derived macrophages in the presence of RANKL and M-CSF, treatment with QOA-8a dose-dependently inhibited the osteoclast formation with an IC50 value of 0.098 µmol/L. QOA-8a also directly acted on osteoblasts, and stimulated new bone formation in murine calvarial bones in vitro and in vivo. In an OVX rat model, administration of QOA-8a (1, 5 mg·kg-1·d-1, po) for 16 weeks effectively prevented OVX-induced bone loss, accompanied by decreased serum levels of the bone resorption marker CTX-1 and increased serum levels of osteoblast marker N-MID-OT. Meaningfully, our preliminary study revealed that QOA-8a down-regulated the ERK1/2 signal in osteoclasts and up-regulated the signal in osteoblasts. QOA-8a showed dual functions in both animal and human osteoclastogenesis and osteoblastogenesis. Our results demonstrate that QOA-8a might serve as a lead compound with a dual function of bone anabolic and anti-resorptive effects in the development of anti-osteoporosis agents.


Assuntos
Reabsorção Óssea/prevenção & controle , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/uso terapêutico , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Quinoxalinas/uso terapêutico , Animais , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Substâncias Protetoras/uso terapêutico , Ligante RANK/farmacologia , Células RAW 264.7 , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
8.
J Ethnopharmacol ; 219: 152-160, 2018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-29126989

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rubia cordifolia is a common traditional Chinese medicine that promotes blood circulation and eliminates blood stasis, and has been used to cure diseases related to blood stasis syndrome (BSS) clinically for many years. It has been previously demonstrated that anti-thrombosis and pro-angiogenesis can improve BSS. However, the anti-thrombotic and pro-angiogenic activities of Rubia cordifolia have not been well investigated. AIM OF STUDY: To determine the potential anti-thrombotic and pro-angiogenic activities of Rubia cordifolia and to elucidate the underlying mechanisms. In addition, the major chemical constituents of Rubia cordifolia extract (QC) were qualitatively analysed by UPLC-Q-TOF/MS to explore the association between pharmacological activity and chemical constituents. MATERIAL AND METHODS: The QC samples were composed of a 95% ethanol extract and an aqueous extract following extraction using 95% ethanol. UPLC-Q-TOF/MS was used to analyse the major chemical constituents of QC. For the anti-thrombotic experiment of QC, a phenylhydrazine (PHZ)-induced AB strain zebrafish thrombosis model was used. The zebrafish larvae were stained using O-dianisidine, and the heart and caudal vein of the zebrafish were observed and imaged with a fluorescence microscope. The staining intensity of erythrocytes in the heart (SI) of each group and the morphology of thrombus in the caudal vein were used to assess the anti-thrombotic effect of QC. For the pro-angiogenic assay of QC, the intersegmental blood vessel (ISV) insufficiency model of Tg(fli-1: EGFP)y1 transgenic zebrafish (Flik zebrafish), which was induced by the VEGF receptor tyrosine kinase inhibitor II (VRI), was used. The morphology of the intact ISVs and defective ISVs was observed to evaluate the pro-angiogenic activity of QC. The mechanism involved in promoting angiogenesis was studied with real-time PCR. RESULTS: A total of 12 components in QC were identified based on standard compounds and references, including nine anthraquinones and three naphthoquinones. After treatment with QC, the PHZ-induced thrombosis in AB strain zebrafish larvae decreased to a certain degree, which we believe was related to its dosages, and the therapeutic effect within the 50-200 µg/mL QC treatment groups was especially prominent (P < 0.01, P < 0.001) compared to that in the PHZ model group. Similarly, QC also recovered the loss of the ISVs, which was induced by VRI in Flik zebrafish larvae, which have a certain dose-effect relationship. The pro-angiogenic activity of QC was also conspicuous (P < 0.01, P < 0.001) compared to that of the VRI model group. The following real-time PCR assay proved that QC significantly restored the VRI-induced downregulation of vWF, VEGF-A, kdrl, and flt-1 in Flik zebrafish (P < 0.05, P < 0.01, P < 0.001). CONCLUSIONS: A total of 12 compounds from QC were analysed by UPLC-Q-TOF/MS. The data of the pharmacological experiments demonstrated that QC presented anti-thrombotic and pro-angiogenic activities in zebrafish, and the principal active components were likely anthraquinones and naphthoquinones. Thus, the current study provided a theoretical basis for the clinical use of Rubia cordifolia as a traditional Chinese medicine in promoting blood circulation and eliminating stasis.


Assuntos
Indutores da Angiogênese/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fibrinolíticos/farmacologia , Rubia , Indutores da Angiogênese/isolamento & purificação , Indutores da Angiogênese/uso terapêutico , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrinolíticos/isolamento & purificação , Fibrinolíticos/uso terapêutico , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/agonistas , Fator A de Crescimento do Endotélio Vascular/biossíntese , Peixe-Zebra
9.
Artigo em Inglês | MEDLINE | ID: mdl-30671128

RESUMO

The traditional processing method for the slices preparation of Rehmanniae roots is time- and energy-consuming and is prone to result in loss of active components during twice water-treatment (once for wash and the other for softening) and drying steps. In this study, we firstly explored an integrative processing technique for Rehmanniae Radix by 2x3 factorial experiment based on the contents of catalpol and verbascoside as measured by HPLC. The potential differences between the traditional stepwise processing technique and the integrative processing technique for catalpol and verbascoside in the prepared slices were investigated. To further confirm the effectiveness of drugs using the integrative processing technique, some pharmacological variables, such as rectal temperature, hematologic parameters (RBC, HGB, HCT, and blood viscosity), and coagulation parameters (TT, APTT, PT and FIB), were detected in a blood-heat and hemorrhage syndrome rat model. Two-way ANOVA analysis showed that drying for 18 h at 50°C was considered as the best combination of process conditions. The mean catalpol and verbascoside contents in the integrative method-processed samples (4.30% and 0.33%, respectively) were higher than those in the traditional method-processed samples (2.61% and 0.21%, respectively). Significant increases in rectal temperature, and hematologic parameters, TT, APTT, and FIB, were observed in the model group rats, compared to the blank group animals (P<0.01). Both in the integrative groups and traditional groups, the extracts caused significant decreases in rectal temperature, RBC, HGB, and HCT with increased concentration compared to the model group animals. All coagulation parameters tested were shortened in model rats received two kind prepared slices. There were no significant therapeutic differences between the integrative and the traditional method-processed slices on the hemostasis and hemorheological parameters in this blood-heat and hemorrhage syndrome rat model, indicating that our integrative method may be a feasible technique for processing Rehmanniae Radix slices.

10.
Artigo em Inglês | MEDLINE | ID: mdl-28359984

RESUMO

Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder affects many adults. Sinomenine, a natural product, has been clinically available for the treatment of RA in China. SND-117, a sinomenine derivative with much more potent activity, might serve as a candidate for anti-arthritis. The aim of the present study was to develop a sensitive and rapid high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for quantification of SND-117 in rat plasma and to understand its absolute bioavailability. The HPLC-MS/MS method was developed and fully validated for determination of SND-117 in rat plasma, and the pharmacokinetic differences were investigated after different administration routes. The pharmacokinetics parameters were calculated by non-compartment model with DAS 3.0 software. After the oral or intravenous administration of different doses of SND-117, the time to peak is 1.5h, half-life time is 8-10h. The absolute oral bioavailability of SND-117 in rats was 9.60%. The results showed that SND-117 in rats was quickly absorbed, slowly eliminate, and the kinetics were linear. This method was suitable for pharmacokinetic studies of SNA-117 in rats.


Assuntos
Antirreumáticos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Morfinanos/sangue , Espectrometria de Massas em Tandem/métodos , Administração Intravenosa , Administração Oral , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/química , Área Sob a Curva , Artrite Reumatoide/tratamento farmacológico , Limite de Detecção , Morfinanos/administração & dosagem , Morfinanos/química , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Zhong Yao Za Zhi ; 41(16): 2975-2980, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28920334

RESUMO

According to the technology requirements of the fourth national survey of Chinese Materia Medica resources (pilot), suitable investigation method of exploration and suggestions for investigating Chinese Materia Medica resources was proposed based on the type of wetland and artificial water of Hongze Lake region. Environment of Hongze Lake and overview of wetland, present situation of ecology and vegetation and vegetation distribution were analyzed. Establishment of survey plan, selection of sample area and sample square and confirmation of representative water area survey plan were all suggested. The present study provide references for improving Chinese materia medica resources survey around Hongze Lake, and improving the technical specifications. It also provide references for investigating Chinese Materia Medica resources survey on similar ecological environment under the condition of artificial intervention.


Assuntos
Conservação dos Recursos Naturais , Materia Medica , Áreas Alagadas , China , Medicamentos de Ervas Chinesas , Ecologia , Lagos , Água
12.
Eur J Pharm Sci ; 76: 33-47, 2015 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-25930119

RESUMO

Tryptophan hydroxylase 1 (Tph-1) initiates the biosynthesis of peripheral serotonin. As peripheral serotonin suppresses bone formation, inhibitor of Tph-1 provides a useful tool to discover anabolic agents for osteoporosis. In the present study, series of ursolic acid (UA) derivatives were synthesized, and their inhibitory activity on serotonin biosynthesis and cytotoxicity were evaluated. Among the derivatives, 8d with potent inhibitory activity on serotonin was applied for further research. The data revealed that 8d significantly inhibited protein and mRNA expressions of Tph-1, and an SPR study indicated that 8d directly interacted to Tph-1 with a binding affinity of KD=15.09µM. Oral administration of 8d significantly prevented bone loss via suppressing serotonin biosynthesis without estrogenic side-effects in ovariectomized (OVX) rats.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Inibidores Enzimáticos/farmacologia , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Serotonina/biossíntese , Triterpenos/farmacologia , Triptofano Hidroxilase/antagonistas & inibidores , Administração Oral , Animais , Sítios de Ligação , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/química , Conservadores da Densidade Óssea/metabolismo , Domínio Catalítico , Modelos Animais de Doenças , Regulação para Baixo , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Simulação de Acoplamento Molecular , Osteoporose Pós-Menopausa/enzimologia , Osteoporose Pós-Menopausa/fisiopatologia , Ovariectomia , Ligação Proteica , Conformação Proteica , RNA Mensageiro/metabolismo , Ratos , Serotonina/sangue , Relação Estrutura-Atividade , Triterpenos/administração & dosagem , Triterpenos/química , Triterpenos/metabolismo , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo
13.
Int Immunopharmacol ; 26(2): 423-31, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25887268

RESUMO

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that affects about 1% of the population worldwide. RA is mainly manifested by persistent synovitis and progressive joint destruction. The aim of the present study was to examine the anti-arthritis effects of SND-117, a sinomenine bivalent that is obtained from the structure modification of a clinically available anti-RA drug, sinomenine. The arthritis model (CIA) was established by immunizing DBA/1 mice with type II collagen, and the arthritis scores including inflammation, joint destruction and bone erosion were assessed after booster immunization for 3weeks. The levels of cytokines such as IL-1ß, IL-6 and TNF-α were analyzed by quantitative PCR and ELISA. The TNF-α induced NF-κB activation in fibroblast-like synovial cells (FLSCs) was analyzed by Western blot. SND-117 significantly relieved the inflammatory symptoms of collagen-induced arthritis, reduced bone erosion and joint destruction in CIA mice. The serum levels of IL-1ß, IL-6 and TNF-α of CIA mice were markedly decreased by SND-117. SND-117 also strongly inhibited the phosphorylation and nuclear translocation of NF-κB p65 in FLSCs upon TNF-α stimulation. These data demonstrated that SND-117 could effectively block the pathogenesis of collagen-induced arthritis in CIA mice via inhibition of NF-κB signaling, and might provide potential clinic benefits in rheumatoid arthritis management.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Fibroblastos/fisiologia , Morfinanos/administração & dosagem , Sinomenium , Sinovite/tratamento farmacológico , Animais , Artrite Reumatoide/imunologia , Osso e Ossos/patologia , Colágeno Tipo II/imunologia , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Imunização Secundária , Mediadores da Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos DBA , Morfinanos/química , NF-kappa B/metabolismo , Sinovite/induzido quimicamente
14.
J Med Chem ; 57(11): 4692-709, 2014 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-24844139

RESUMO

Tryptophan hydroxylase 1 (Tph-1), the principal enzyme for peripheral serotonin biosynthesis, provides a novel target to design anabolic agents for osteoporosis. Here, we present a design, synthesis of a novel series of ursolic acid derivatives under the guidance of docking technique, and bioevaluation of the derivatives using RBL2H3 cells and ovariectomized (OVX) rats. Of the compounds, 9a showed a potent inhibitory activity on serotonin biosynthesis. Further investigations revealed that 9a, as an efficient Tph-1 binder identified by SPR (estimated KD: 6.82 µM), suppressed the protein and mRNA expressions of Tph-1 and lowered serotonin contents in serum and gut without influence on brain serotonin. Moreover, oral administration of 9a elevated serum level of N-terminal propeptide of procollagen type 1 (P1NP), a bone formation marker, and improved bone microarchitecture without estrogenic side effects in ovariectomized rats. Collectively, 9a may serve as a new candidate for bone anabolic drug discovery.


Assuntos
Anabolizantes/síntese química , Osso e Ossos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Triterpenos/síntese química , Triptofano Hidroxilase/metabolismo , Anabolizantes/química , Anabolizantes/farmacologia , Animais , Osso e Ossos/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Humanos , Simulação de Acoplamento Molecular , Osteoporose/metabolismo , Ovariectomia , Ligação Proteica , Quinoxalinas/síntese química , Quinoxalinas/química , Quinoxalinas/farmacologia , RNA Mensageiro/metabolismo , Ratos , Serotonina/biossíntese , Relação Estrutura-Atividade , Ressonância de Plasmônio de Superfície , Triterpenos/química , Triterpenos/farmacologia , Triptofano Hidroxilase/genética
15.
Zhongguo Zhong Yao Za Zhi ; 30(9): 669-70, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-16075729

RESUMO

OBJECTIVE: To establish the determination method of pulegone in Herba Schizonepetae. METHOD: HPLC method was developed for the determination of pulegone in Herba Schizonepetae. The separation was performed on C18 column with MeOH-H2O (80:20) as a mobile phase. The detection wavelength was set at 252 nm. RESULT: The quantitation of pulegone in Herba Schizonepetae varied from 0.2-0.7 mg x g(-1). The average recovery is 96.2%, RSD 0.81%. CONCLUSION: The method is simple, rapid and accurate.


Assuntos
Medicamentos de Ervas Chinesas/química , Lamiaceae/química , Monoterpenos/análise , Plantas Medicinais/química , Cromatografia Líquida de Alta Pressão/métodos , Componentes Aéreos da Planta/química , Reprodutibilidade dos Testes
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