Dihydromyricetin reverses Herceptin resistance by up-regulating miR-98-5p and inhibiting IGF1R/HER2 dimer formation in SKBR3 cells / 南方医科大学学报

OBJECTIVE@#To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells.@*METHODS@#The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation.@*RESULTS@#The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05).@*CONCLUSION@#Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.

Antibacterial activity of 3, 3', 4'-Trihydroxyflavone from Justicia wynaadensis against diabetic wound and urinary tract infection

ABSTRACT The present investigation was designed to study the effect of an active compound isolated from Justicia wynaadensis against multi drug resistant organisms (MDRO's) associated with diabetic patients. The drug resistant pathogens implicated in wound and urinary tract infection of diabetic patients were isolated and identified by molecular sequencing. Solvent-solvent fractionation of crude methanol extract produced hexane, chloroform, ethyl acetate and methanol-water fraction, among which chloroform fraction was found to be potent when compared with other three fractions. Further, chloroform fraction was subjected to preparatory HPLC (High-Performance Liquid Chromatography), that produced four sub-fractions; chloroform HPLC fraction 1 (CHF1) through CHF4. Among the sub-fractions, CHF1 inhibited the pathogens effectively in comparison to other three sub-fractions. The purity of CHF1 was found to be >95%. Therefore, CHF1 was further characterized by NMR and FTIR analysis and based on the structure elucidated, the compound was found to be 3,3',4'-Trihydroxyflavone. The effective dose of this bioactive compound ranged from 32 µg/mL to 1.2 mg/mL. Thus, the present study shows that 3,3',4'-Trihydroxyflavone isolated from J. wynaadensis is an interesting biopharmaceutical agent and could be considered as a source of antimicrobial agent for the treatment of various infections and used as a template molecule for future drug development.

Lipophilicity and antibacterial activity of flavonols: antibacterial activity of resinous exudates of Haplopappus litoralis, H. chrysantemifolius and H. scrobiculatus / Lipofilia y actividad antibacteriana de flavonoles: actividad antibacteriana de los exudados resinosos de Haplopappus litoralis, H. chrysantemifolius y H. scrobiculatus

The antibacterial properties of the resinous exudates from Haplopappus litoralis, H. chrysantemifolius and H. scrobiculatus from Central Chile were assessed against Gram negative and Gram-positive bacteria, and proved active against the latter. The results show that the antibacterial activities of the resinous exudates are independent from the flavonols isolated from each extract that proved to be inactive. The estimated lipophilicity of the flavonols isolated from the Haplopappus resinous exudates were compared with the lipophilicity of known antibacterial flavonols. This analysis showed that lipophilicity is an important variable to predict the antibacterial activity of flavonols.

La actividad antibacteriana de los exudados resinosos de Haplopappus litoralis, H. chrysantemifolius y H. scrobiculatus de la Zona Central de Chile fueron evaluadas frente a bacterias Gram-negativas y Gram-positivas, y resultaron activos frente a estas últimas. Los resultados mostraron que la actividad antibacteriana de los exudados resinosos es independiente de los flavonoles aisladas de cada extracto que no mostraron actividad antibacteriana. La lipofilia estimada de los flavonoles aislados de los exudados resinosos de Haplopappus se comparó con la lipofilia de conocidos flavonoles antibacterianos. Este análisis mostró que la lipofilia es una variable importante para predecir la actividad antibacteriana de los flavonoles.

Inhibition of peroxidase activity and scavenging of reactive oxygen species by astilbin isolated from Dimorphandra mollis (Fabaceae, Caesalpinioideae)

Astilbin (5,7,3’,4’-tetrahydroxy-2,3-dihydroflavonol-3-ß-o-rhamnoside), a flavonoid with a large range of biological activities, was isolated from Dimorphandra mollis, a shrub common to the Brazilian Cerrado. The purpose of this study is to verify the effects of astilbin on myeloperoxidase (MPO) and horseradish peroxidase (HRP), and its antioxidant activity against hypochlorous acid (HOCl) and total antioxidant activity (TAC) by the 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+). Astilbin inhibited MPO and HRP activities in a concentration-dependent relationship and effectively scavenged HOCl. The TAC by ABTS•+ of astilbin (IC50 ~ 20 mM) was higher than that of uric acid, which was used as a positive control. These data demonstrate that astilbin is a potent antioxidant and that it inhibits MPO and HRP activities efficiently.