RESUMO
Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20â µM (P<0.01) and 40â µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40â µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.
Assuntos
Anti-Inflamatórios , Simulação de Acoplamento Molecular , Óxido Nítrico , Solanum , Solanum/química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Farmacologia em Rede , Amidas/química , Amidas/farmacologia , Amidas/isolamento & purificação , Camundongos , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Linhagem Celular , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificaçãoRESUMO
The transcription suppressor factor FBI-1 (the factor that binds to inducer of short transcripts-1) is an important regulator of hepatocellular carcinoma (HCC). In this work, the results showed that FBI-1 promoted the Warburg effect and enhances the resistance of hepatocellular carcinoma cells to molecular targeted agents. Knockdown of FBI-1 via its small-interfering RNA (siRNA) inhibited the ATP level, lactate productions, glucose uptake or lactate dehydrogenase (LDH) activation of HCC cells. Transfection of siFBI-1 also decreased the expression of the Warburg-effect-related factors: hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), or GLUT1, and the epithelial-mesenchymal transition-related factors, Vimentin or N-cadherin. The positive correlation between the expression of FBI-1 with HIF-1α, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1α by binding to the 3'-untranslated region (3'-UTR) of HIF-1α in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1α and HIF-1α pathway's activation by repressing the expression of miR. By modulating the miR-30c/HIF-1α, FBI-1 promoted the Warburg effect or the epithelial-mesenchymal transition of HCC cells and promoted the resistance of HCC cells to molecular targeted agents.