RÉSUMÉ
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Sujet(s)
Animaux , Lapins , Fibrillation auriculaire/métabolisme , Protéine-1 de type kelch associée à ECH/métabolisme , Transduction du signal , Facteur-2 apparenté à NF-E2/pharmacologie , Simulation de docking moléculaire , Stress oxydatif , Métabolisme énergétique , Mitochondries/métabolisme , Inflammation/métabolisme , Heme oxygenase-1RÉSUMÉ
We have carried out the chemical investigation on the roots of Alangium chinense. The chemical constituents from the roots of A.chinense were isolated and purified by various chromatographic techniques, such as silica gel, MCI-Gel resin, Sephadex LH-20 and high performance liquid chromatography. As a result, three alkaloids (1-3) were isolated from 90% EtOH extracts of the roots of this plant. Their structures were elucidated by physical-chemical properties and spectral data. Among them, compound 1 is a new compound, determined as 8-hydroxy-3-hydroxymethyl-6,9-dimethyl-7H-benzo[de]isoquinolin-7-one. Cytotoxicity of the compounds was evaluated by the MTT method. Compound 1 displayed cytotoxicity against NB4, A-549, SHSY5Y, PC-3 and MCF-7 cell lines with IC₅₀ values of 4.2, 3.5, 5.7, 2.8 and 3.9 μmol•L⁻¹, respectively.
RÉSUMÉ
The phytochemistry investigation on the Cassia occidentalis, a Dai Medicine, was carried out. The C. occidentalis was extracted with ethanol and then partitioned with EtOAc. The EtOAc soluble materials were subjected repeatedly to column chromatography on silica gel and preparative RP-HPLC, leading to isolation of a nor-sesquiterpene, 3-isopropyl-1,6-dimethoxy-5-methyl-naphthalen-7-ol (1), and a sesquiterpene, 2,7-dihydroxy-4-isopropyl-6-methyl-naphthalene-1-carbaldehyde (2). Their structures were determined by means of spectroscopic studies. Compound 1 is a new compound. Compound 2 is also isolated from C. occidentalis for the first time. In addition, the cytotoxicity of compound 1 for NB4, A549, SHSY5Y, PC3, and MCF7 cells line was assayed by using the MTT method, and it displayed potential cytotoxicity for the tested cancer cell-line with IC₅₀ valves of (1.8±0.2), (1.2±0.2), (0.9±0.1), (2.2±0.3), (2.6±0.3) μmol•L⁻¹, respectively.
RÉSUMÉ
A new furan-2-carboxylic acid, 5-[3-(hydroxymethyl)-4,5-dimethoxyphenyl]-3-methylfuran-2-carboxylic acid(1),has been isolated from the bark of Cassia alata by using various chromatographic techniques. It displayed cytotoxicity against NB4, A549, SHSY5Y, PC3 and MCF7 cell lines with IC₅₀ values of 2.5, 1.2, 2.2, 3.6 and 1.9 μmol•L⁻¹, respectively.
RÉSUMÉ
A new isoindole alkaloid (1), has been isolated from the leaves of Cassia siamea by using various chromatographic techniques. Compound 1 is a new compound, determined as 5-(hydroxymethyl)-2-methyl-6-prenylisoindolin-1-one, and it displayed cytotoxicity against NB4, A549, SHSY5Y, PC3 and MCF7 cell lines with IC₅₀ values of 3.2,4.6,2.8,6.4, 2.5 μmol•L⁻¹, respectively.
RÉSUMÉ
For the purpose of finding new bioactive agents from ethnic medicines, the chemical study on Dai Medicine Cassia occidentalis was carried out. The chemical constituents from the seeds of C. occidentalis were isolated by column chromatographic methods on silica gel, MCI-Gel resin, Sephadex LH-20, and high performance liquid chromatography. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. The cytotoxicity of the compound for NB4, A549, SHSY5Y, PC3, and MCF7 cells line was also assayed by using the MTT method. Two sesquiterpenes (1 and 2) were isolated from this plant. Compound 1 is a new compound and named as methyl 6-(hydroxymethyl)-4-isopropyl-7-methoxynaphthalene-1-carboxylate. Compound 1 also displayed high cytotoxicity with the tested cancer cell-lines.
RÉSUMÉ
Objective: For the purpose of finding new bioactive agents from ethnic medicines, the chemical study on Dai Medicine Cassia alata was carried out. Methods: The chemical constituents from the twigs of C. alata were isolated by column chromatographic methods of silica gel, MCI-Gel resin, Sephadex LH-20, and HPLC. The structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. The cytotoxicity of this compound for NB-4, A-549, SHSY5Y, PC-3, and MCF-7 cells line was also evaluated by using the MTT method. Results: Four 2-arylbenzofuran compounds were isolated from this plant and identified as 7- methoxy-2-(4-methoxyphenyl)-3,5-dimethylbenzofuran (1), moracin N (2), 2-(2'-methoxy-4'-hydroxy-aryl)-3-methy-6-hydroxybenzofuran (3), and moracin P (4). Conclusion: Compound 1 is a new compound named as 7-methoxy-2-(4-methoxyphenyl)-3,5-dimethylbenzofuran. Compound 1 also displays the high cytotoxicity to tested cancer cell-line.
RÉSUMÉ
OBJECTIVE: To investigate the relationship between the ovarian response, induced by gonadotropin hormone, and levels of follicle-stimulating hormone receptor (FSHR). METHODS: The level of ovarian response was divided into three groups based on the number of follicles obtained during oocyte retrieval: poor responders (<4 follicles), normal responders (4 approximate, equals 13) and high responders(>13 follicles). FSHR mRNA was measured using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The expression of FSHR mRNA in the poor responders was 0.54+/-0.07. This was much lower than that of the normal responders who were at 0.90+/-0.17,and the high responders who were at 1.20+/-0.45(P<0.05). CONCLUSION: Ovarian response induced by gonadotropin hormone stimulation is correlated with the level of FSHR mRNA in the granulosa cells.