RESUMO
The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66â µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.
Assuntos
Cumarínicos , NF-kappa B , NF-kappa B/metabolismo , Cumarínicos/farmacologia , Cumarínicos/metabolismo , Anti-Inflamatórios/farmacologia , Extratos Vegetais/química , Transdução de Sinais , Lipopolissacarídeos/farmacologiaRESUMO
A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities inâ vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96â µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.
Assuntos
Amidas , Ciclo-Oxigenase 2 , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Sulfonamidas , Animais , Camundongos , Células RAW 264.7 , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Relação Estrutura-Atividade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Estrutura Molecular , Relação Dose-Resposta a Droga , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/químicaRESUMO
Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC50 values ranging from 1.35 to 5.93 µM, which were more effective than the positive control indomethacin (IC50 = 13.18 µM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα.