RESUMO
This research was designed to explore the effect of Ma Xing Shi Gan decoction (MXD) in alleviating particulate matter less than 2.5 µm in diameter (PM2.5) induced lung injury from the perspective of epithelial barrier protection and inhibition of epithelial-to-mesenchymal transition (EMT). Rats were exposed to PM2.5 to establish a lung injury model in vivo, and a PM2.5-stimulated primary cultured type II alveolar epithelial cell model was introduced in vitro. Our results indicated that MXD alleviated the weight loss and pathologic changes and improved the epithelial barrier dysfunction. MXD also significantly inhibited the TGF-ß/Smad3 pathway, increased the level of ZO-1 and claudin-5, and reversed the EMT process. Notably, the protection of MXD was abolished by TGF-ß in vitro. Our results indicated that MXD has a protection against PM2.5-induced lung injury. The proposed mechanism is reversing PM2.5-induced EMT through inhibiting TGF-ß/Smad3 pathway and then upregulating the expression of tight-junction proteins.
RESUMO
Ma Xing Shi Gan Decoction (MXD), a classical traditional Chinese medicine prescription, is widely used for the treatment of upper respiratory tract infection. However, the effect of MXD against particulate matters with diameter of less than 2.5 µm (PM2.5) induced lung injury remains to be elucidated. In this study, rats were stimulated with PM2.5 to induce lung injury. MXD was given orally once daily for five days. Lung tissues were harvested to assess pathological changes and edema. Myeloperoxidase (MPO) activity and malonaldehyde (MDA) content in lung were determined to evaluate the degree of injury. To assess the barrier disruption, the bronchoalveolar lavage fluid (BALF) was collected to determine the total protein content and count the number of neutrophils and macrophages. For evaluating the activation of macrophage in lung tissue, CD68 was detected using immunohistochemistry (IHC). The levels of inflammatory factors including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6) in BALF and serum were measured. In vitro, a PM2.5-activated RAW 264.7 macrophages inflammatory model was introduced. To evaluate the protective effect of MXD-medicated serum, the cell viability and the release of inflammatory factors were measured. The effects of MXD on the High mobility group box-1/Toll-like receptor 4/Nuclear factor-kappa B (HMGB1/TLR4/NFκB) pathway in lung tissue and RAW 264.7 cells were assessed by Western blot. For further confirming the protective effect of MXD was mediated by inhibiting the HMGB1/TLR4/NFκB pathway, RAW 264.7 cells were incubated with MXD-medicated serum alone or MXD-medicated serum plus recombinant HMGB1 (rHMGB1). MXD significantly ameliorated the lung injury in rats, as evidenced by decreases in the pathological score, lung edema, MPO activity, MDA content, CD68 positive macrophages number, disruption of alveolar capillary barrier and the levels of inflammatory factors. In vitro, MXD-medicated serum increased cell viability and inhibited the release of inflammatory cytokines. Furthermore, MXD treatment was found to inhibit HMGB1/TLR4/NFκB signal pathway both in vivo and in vitro. Moreover, the protection of MXD could be reversed by rHMGB1 in RAW 264.7. Taken together, these results suggest MXD protects rats from PM2.5 induced acute lung injury, possibly through the modulation of HMGB1/TLR4/NFκB pathway and inflammatory responses.
RESUMO
Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.
Assuntos
Berberina/uso terapêutico , Proteína HMGB1/antagonistas & inibidores , Infarto da Artéria Cerebral Média/tratamento farmacológico , Subunidade p50 de NF-kappa B/antagonistas & inibidores , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/patologia , Edema Encefálico/tratamento farmacológico , Regulação para Baixo , Ácido Glicirrízico/uso terapêutico , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Infarto da Artéria Cerebral Média/etiologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Traumatismo por Reperfusão/complicações , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
(3ß,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX001), a derivative of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effect of JLX001 on cerebral ischemia and researchits antiplatelet and antithrombosis activities via thromboxane (TXA2)/phospholipase C-ß-3(PLCß3)/protein kinase C (PKC) pathway suppression. The therapeutic effects of JLX001 was evaluated by infarct sizes, brain edema and neurological scores in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Brain TXA2 and prostacyclin (PGI2) were measured by enzyme-linked immunosorbentassay (ELISA). P-PLCß3and activated PKC were detected by immunohistochemical method. Adenosine diphosphate (ADP) or 9, 11-dieoxy-11α, 9α-epoxymethanoeprostaglandin F2α (U46619) was used as platelet agonist in the in vivo and in vitro platelet aggregation experiments. Clotting time and bleeding time were determined. Besides, two whole-animal experiments including arteriovenous shunt thrombosis and pulmonary thromboembolism model were conducted. Results showed that JLX001 treatment markedly alleviated cerebral infarcts, edema, and neurological scores in permanent middle cerebral artery occlusion (pMCAO) rats. Brain TXA2 level, p-PLCß3and activated PKC were decreased, while PGI2level had no significant change. Besides, JLX001 inhibited platelet aggregation induced by ADP or U46619 and exhibited anti-coagulation effects with a minor bleeding risk. In the two whole-animal experiments, JLX001 inhibited thrombus formation. In summary, JLX001 attenuates cerebral ischemia injury and the underlying mechanisms relate to inhibiting platelet activation and thrombus formation via TXA2/PLCß3/PKC pathway suppression.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/prevenção & controle , Trombose Intracraniana/prevenção & controle , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Aspirina/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Edema Encefálico/sangue , Edema Encefálico/patologia , Edema Encefálico/prevenção & controle , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Epoprostenol/metabolismo , Feminino , Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/enzimologia , Infarto da Artéria Cerebral Média/patologia , Trombose Intracraniana/sangue , Trombose Intracraniana/enzimologia , Trombose Intracraniana/patologia , Masculino , Camundongos Endogâmicos ICR , Fosfolipase C beta/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Proteína Quinase C/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tromboxano A2/metabolismo , Triterpenos/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. AIM OF THE STUDY: The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism. MATERIALS AND METHODS: Following induction of cerebral ischemia in rats by permanent middle cerebral artery occlusion (pMCAO). Neurological defect score, cerebral blood flow, infarct size, and brain edema were measured to evaluate the injury. Arteriovenous shunt thrombosis model and adenosine 5'-diphosphate (ADP) induced acute pulmonary embolism model were conducted to estimate the antithrombotic effect of SCED. In order to investigate the effects of SCED on platelet aggregation, rat platelet-rich-plasma (PRP) were incubated with SCED prior to the addition of the stimuli (ADP or 9, 11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α (U46619)). Aggregation was monitored in a light transmission aggregometer. Inhibitory effect of SCED on thromboxane A2 (TXA2) release was detected by ELISA kit. Phospholipase C (PLC)/ Protein kinase C (PKC) signaling pathway was analyzed by a Western blot technique. The effect of the SCED was also studied in vivo on bleeding time in mice. RESULTS: SCED improved the neurological defect score, increased cerebral blood flow, reduced infarct size and alleviated brain edema in rats exposed to pMCAO. After administration of SCED, thrombosis formation in arteriovenous shunt was inhibited and recovery time in pulmonary embolism was shortened. The inhibitory effect of SCED on platelet activation was further confirmed by TXB2 ELISA kit and Western blot analysis of PLC/PKC signaling pathway. CONCLUSIONS: SCED attenuates cerebral ischemic injury. The possible mechanism is that SCED inhibits thrombosis formation, platelet aggregation and activation of PLC/PKC pathway. On this basis, this new extract could be a promising agent to inhibit thrombosis formation and protect against cerebral ischemia injury.
Assuntos
Isquemia Encefálica/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Salvia miltiorrhiza/química , Acidente Vascular Cerebral/prevenção & controle , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Infarto da Artéria Cerebral Média , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ativação Plaquetária/efeitos dos fármacos , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Trombose/tratamento farmacológico , Fosfolipases Tipo C/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Shuang-Qi gout capsule, a traditional Chinese medicine prescription, has been used in the treatment of, gout arthritis, arthralgia and inflammation. Since renal urate overload associated with severe disability including gout, elimination of excess renal uric acid is highly essential. Therefore, in this study we evaluated the antihyperuricemic and the renoprotective effect of the Shuang Qi gout capsule (SQ) with elucidation of its mechanism. MATERIALS AND METHODS: We assessed the antihyperuricemic activity of SQ on urinary and serum uric acid, creatinine, blood urea nitrogen, fractional excretion of uric acid (FEUA) and glomerular filtration rate of creatinine and uric acid in potassium oxonate (PO) - induced mice as well as in non-induced mice. To illuminate the mechanism of antihyperuricemic activity, we investigated renal transport activity and the expression of mRNA levels in PO-induced and non-induced mice by western blot and RT-PCR methods. RESULTS: SQ showed significant reduction in serum uric acid, creatinine and blood urea nitrogen levels and marked elevation of urine uric acid, creatinine and FEUA levels only in hyperuricemic mice. Furthermore, SQ could recover the altered expressions of proteins and mRNA levels of all the main renal transporters significantly in dose dependent manner. CONCLUSIONS: SQ could effectively regulate the main renal transporters denoted its denote probable antihyperuricemic mechanism of SQ and its dose dependent uricosuric effect. In addition, SQ attenuated the deleterious effects of hyperuricemia with renal dysfunction. Thus SQ could be a potent antihyperuricemic agent which can perform as a safer and effective agent in the management of hyperuricemia via regulating the renal transporters.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Supressores da Gota/farmacologia , Gota/metabolismo , Substâncias Protetoras/farmacologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Cápsulas , Proteínas de Transporte/metabolismo , Creatinina/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Gota/induzido quimicamente , Gota/tratamento farmacológico , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos ICR , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ácido Oxônico , Substâncias Protetoras/uso terapêutico , Membro 5 da Família 22 de Carreadores de Soluto , Simportadores , Ácido Úrico/sangue , Ácido Úrico/urinaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Clematichinenoside AR (AR) has been defined as a major active ingredient of triterpenoid saponins extracted from Clematidis Radix et Rhizoma, which is a traditional Chinese herbal medicine that has long been used in the treatment of rheumatoid arthritis (RA). To further explore the mechanism of AR in the treatment of RA, we investigated whether its immunomodulatory effects are related to Treg-mediated suppression derived from Peyer׳s patches (PPs) in adjuvant induced arthritis (AIA) rat model. MATERIALS AND METHODS: AR (8, 16, 32 mg/kg) was orally administered daily from Day 18 to Day 31 after immunization. The effect of AR on AIA rats was evaluated by hind paw swelling and histopathological examination. Percentages of CD4(+)CD25(+)Foxp3(+) T regulatory cells were determined by flow cytometry. Levels of IL-10, TGF-ß1, IL-17A and TNF-α were measured by ELISA. Expressions of Foxp3 and RORγ in synovium were detected using immunohistochemical analysis. RESULTS: AR treatment significantly reduced paw swelling of AIA rats, and histopathological analysis confirmed it could suppress severity of established arthritis. AR treatment upregulated the percentages of CD4(+)CD25(+)Foxp3(+) Treg cells among CD4+ T cells in PPs lymphocytes, and increased the levels of IL-10 and TGF-ß1 secreted from ConA-activated PPs lymphocytes, whereas decreased the levels of IL-17 A and TNF-α. Similar tendency of circulating CD4(+)CD25(+)Foxp3(+) Treg cells percentages and serum cytokine levels were observed. Moreover, AR decreased the expression levels of Foxp3 and RORγ in joint synovial membrane. CONCLUSIONS: In conclusion, these results suggested AR has a potent protective effect on the progression of AIA, probably by augmenting CD4(+)CD25(+)Foxp3(+) Treg cells in PPs to induce immunosuppression, and modulating the balance between Treg cells and Th17 cells systemically. These findings may help to develop AR as a potent immunosuppressive agent for the treatment of RA.
Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Imunossupressores/farmacologia , Articulações/efeitos dos fármacos , Nódulos Linfáticos Agregados/efeitos dos fármacos , Saponinas/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Progressão da Doença , Relação Dose-Resposta a Droga , Adjuvante de Freund , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Articulações/imunologia , Articulações/metabolismo , Masculino , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/metabolismo , Fitoterapia , Plantas Medicinais , Ratos Sprague-Dawley , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo , Fatores de TempoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Shuang-Qi gout capsule is a traditional Chinese medicine prescription, which has been used in the treatment of joint pain, inflammation and gout arthritis. This study evaluates anti-inflammatory and antinociceptive effects of Shuang-Qi gout capsule and its modulation of pro-inflammatory cytokines with special reference to gout arthritis. MATERIALS AND METHODS: Anti-inflammatory effect of Shuang-Qi gout capsule was investigated bymice tail-flick response, acetic acid induced writhing response, Xylene-induced auricle inflammation and the hind paw volume of the monosodium urate (MSU) crystal induced rats with different time durations. To investigate the effects on gout arthritis, ankle joint of rats induced by MSU crystals and assessed for edema and histopathological changes. In vitro, prepared serum was incubated with urate crystal induced HUVE cells and the release of TNF-α and IL-1ß determined by ELISA. RESULTS: Shuang-Qi gout capsule showed significant and dose dependent anti-inflammatory effect via reducing edema and pain, throughout all the models. The high dose of Shuang-Qi gout capsule and Indomethacin significantly attenuated the edema. Histopathological results showed that high and medium dose of Shuang-Qi gout capsule and Indomethacin reduced gouty joint inflammatory features, while the high dose of Shuang-Qi gout capsule showed a better therapeutic effect. High and medium dose of Shuang-Qi gout capsule significantly reduced the release of TNF-α and IL-1ß (p<0.05). CONCLUSION: Shuang-Qi gout capsule can effectively inhibit the inflammation, analgesia, through the modulation of emission of pro-inflammatory cytokines and the curative effect is dose dependent. Conversely, these MSU induced in vivo and in vitro studies of Shuang-Qi gout capsule suggest that, Shuang-Qi gout capsule may be a potential agent for treatment in gouty arthritis.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Gotosa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Dor/tratamento farmacológico , Ácido Acético , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Artrite Gotosa/induzido quimicamente , Cápsulas , Células Cultivadas , Citocinas , Medicamentos de Ervas Chinesas/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Feminino , Temperatura Alta , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-1beta/metabolismo , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Dor/etiologia , Fitoterapia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico , XilenosRESUMO
The root of Clematis chinensis Osbeck has been used widely in rheumatoid arthritis in Chinese traditional medicine, and AR-6 is a triterpene saponin isolated from it. In this present study, we investigated the in vivo effects of oral AR-6 in chronic rat with collagen-induced arthritis (CIA) and possible molecular mechanism. CIA was induced by immunizing 56 female Sprague-Dawley (SD) rats with chicken typeIIcollagen (CII). Following eighteen days, the immunization rats with CIA were treated with AR-6 (32, 16, 8 mg/kg), cyclophosphamide (7 mg/kg), and TGP (Total Glucosides of Paeonia) (180 mg/kg) for 7 days, and rats without CIA were given the same volume of purified water. TNF-α and IL-1ß levels in peripheral blood will be measured by ELISA, and Western blot analysis will be used to detect the expression of NF-κB p65 subunits, TNF-α and COX-2, in synovial membrane. We found that therapeutic treatment with AR-6 markedly improves the paw swelling and histopathological changes. Moreover, the serum levels of pro-inflammatory cytokines TNF-α and IL-1ß were markedly lowered, and the expression of NF-κB p65 subunits, TNF-α and COX-2, in the synovial membrane of CIA rats was significantly inhibited in the AR-6-treated groups. These results enable to prove that AR-6 has a potential anti-inflammatory effect in CIA rats, and its mechanism may relate to the inhibition of the expression of NF-κB p65 subunits, TNF-α and COX-2.
Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Clematis , Ciclo-Oxigenase 2/metabolismo , Mediadores da Inflamação/metabolismo , Extratos Vegetais/farmacologia , Membrana Sinovial/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anti-Inflamatórios/isolamento & purificação , Artrite Experimental/sangue , Artrite Experimental/induzido quimicamente , Artrite Experimental/enzimologia , Artrite Experimental/imunologia , Western Blotting , Clematis/química , Colágeno Tipo II , Ciclofosfamida/farmacologia , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Glucosídeos/farmacologia , Mediadores da Inflamação/sangue , Interleucina-1beta/sangue , Paeonia , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Membrana Sinovial/enzimologia , Membrana Sinovial/imunologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangueRESUMO
Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Tetra-Hidroisoquinolinas/síntese química , Tetra-Hidroisoquinolinas/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Doxorrubicina/metabolismo , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Resistência a Múltiplos Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Humanos , Concentração Inibidora 50 , Células K562 , Terapia de Alvo Molecular , Óxido Nítrico/metabolismo , Rodamina 123/metabolismo , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/metabolismo , Triazóis/química , Triazóis/metabolismo , Verapamil/metabolismo , Verapamil/farmacologiaRESUMO
Tanshinone A is a novel derivative of phenanthrene-quinone extracted from Salvia miltiorrhiza BUNGE, a traditional herbal medicine. Cytotoxic effect of tanshinone A was observed in this study. Additionally its mechanism of promoting apoptosis was also investigated. MTT and SRB assays were applied to measure the effects of tanshinone A on the cell viability, the cell cycle distribution and cell apoptosis were measured by flow cytometry using PI staining and Annexin V/PI double staining method respectively. The changes of mitochondrial membrane potential were also detected by flow cytometry. Spectrophotometric method was used to detect the changes of caspase-3 activity. Western blotting assay was used to evaluate the expression of bcl-2, bax and c-Myc proteins. Results indicated that tanshinone A displayed a significant inhibitory effect on the growth of K562 cells in a dose- and time-dependent manner, and showed obvious minor damage to LO2 cells. Tanshinone A could arrest K562 cells in the G(0)/G(1) phase and induce apoptosis, decrease the mitochondrial transmembrane potential, decrease the expressions of bcl-2 and c-Myc proteins, increase the expression of bax protein and the activity of caspase-3. Accordingly, it was presumed that the apoptosis induction may be through the endogenous pathway. Subsequently, tanshinone A could be a promising candidate in the development of a novel antitumor agent.
Assuntos
Abietanos/química , Abietanos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Leucemia Eritroblástica Aguda/patologia , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células K562 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismoRESUMO
The root of Clematis chinensis Osbeck has been used widely in rheumatoid arthritis in Chinese traditional medicine and AR-6 is a triterpene saponin isolated from it. In this present study, we investigated in vivo effects of oral AR-6 in chronic rat adjuvant-induced arthritis (AA) and in vitro effect in macrophage and synoviocytes cells. Arthritic scores and serum inflammatory mediators were evaluated 19 days after AA induction by endermic injection of Freund's complete adjuvant in Sprague-Dawley(S-D) rats. Oral administration of AR-6 to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. The synoviocyte and macrophage response ex vivo were then analyzed. Anti-arthritic effects of AR-6 correlated with significant decrease of NO and TNF-alpha produced by peritoneal macrophages, ex vivo and in vitro. AR-6 also significant decreased the proliferation of synoviocyte. These data indicate that AR-6 is a potential anti-inflammatory therapeutic and preventive agent.
Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Saponinas/administração & dosagem , Triterpenos/administração & dosagem , Administração Oral , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Mediadores da Inflamação/sangue , Macrófagos Peritoneais/imunologia , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Líquido Sinovial/citologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A new triterpenoid saponin named clematichinenoside AR(2), along with the six known compounds, was isolated and characterized from Clematis chinensis Osbeck (Ranunculaceae), a commonly used traditional Chinese medicine with anti-inflammatory and anti-rheumatoid activities. The structure of the new saponin was elucidated as 3-O-beta-[(O-alpha-L-rhamnopyranosyl-(1 --> 6)-O-beta-D-glucopyranosyl-(1 --> 4)-O-beta-D-glucopyranosyl-(1 --> 4)-O-beta-D-ribopyranosyl-(1 --> 3)-O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl)oxy]olean-12-en-21alpha-hydroxy-28-oic acid-O-alpha-L-rhamnopyranosyl-(1 --> 4)-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (1) by spectral analysis and chemical methods. The effects of two major saponins (clematichinenosides AR and AR(2)) on the secretion of TNF-alpha in murine peritoneal macrophages induced by lipopolysaccharides were further investigated. The result indicated that a majority of triterpenoid saponins of this herb may be useful in the exploration of lead compounds for the treatment of some autoimmune diseases.
Assuntos
Clematis/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Plantas Medicinais/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Raízes de Plantas/química , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
OBJECTIVE: To observe the effects of Naomaitai capsule on the learning and memory abilities and the content of acetylcholine(Ach) in the brain tissue of the model rat. METHOD: One vascular dementia(VD) model was produced by occlusion of bilateral common carotid arteries in rats with following steps: ischemia 20 minutes-reperfusion 10 minutes-ischemia 20 minutes. The learning and memory abilities were tested by water maze. The other VD model was formed by 4-vessel occlusion-reperfusion injury in rats. The time of right reflect recovery and the content of Ach in the brain tissue were determined. RESULT: Naomaitai capsule can significantly improve the learning and memory abilities of the dementia rats( P < 0.05, P < 0.01), increase the content of Ach (P < 0.05, P < 0.01) and reduce the time of right reflect recovery(P < 0.01). CONCLUSION: Naomaitai capsule can improve the learning and memory abilities by increasing the content of Ach of the VD rats.