CHEMICAL & PHARMACEUTICAL BULLETIN
·
2019
·Vol. 67
·期 9
·1006-1014
·
IF 1.405
Pan Yu,Chao-Jie Xia,Dong-Dong Li,Zhenzhong Wang,Wei Xiao,Lin-Guo Zhao
Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.
研究领域:
药理学
·
药物化学
·
药物研发
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 9
·e13898
·
IF 2.72
Jing-Yu Duan,Wei Chen,Yang-Qi Zhao,Liang-Liang He,En-Chao Li,Zhong-Hui Bai,Yong-Jian Wang,Chun-Ping Zhang
Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound-healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin-resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)-treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n -dotriacontanol ( 1 ), shikimic acid ( 2 ), 1- O -caffeoylquinic acid methyl ester ( 3 ), 5- O -caffeoylquinic acid methyl ester ( 4 ), 5- O -coumaroylquinic acid methyl ester ( 5 ), 5- O -caffeoylquinic acid butyl ester ( 6 ), quercetin-3- O - α - L -rhamnoside ( 7 ), quercetin ( 8 ), quercetin-3- O -(4״-methoxy) -α-L -rahmnopyranosyl ( 9 ), hyperoside ( 10 ), and rutin ( 11 ). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin-resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 μM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 μM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA-treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. Practical applications Hypericum patulum is a well-known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin-resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA-treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1 , 2 , 3 , 5 , 6 , 9 , 10 , and 11 were isolated from the plant for the first time. Quercetin-3- O -(4"-methoxy)- α - L -rahmnopyranosyl ( 9 ) and hyperoside ( 10 ) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum .
研究领域:
药理学
·
生物化学
·
细胞生物学
·
药用植物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）