Effects of caffeoylquinic acid analogs derived from aerial parts of Artemisia iwayomogi on adipogenesis

Abstract

Artemisia iwayomogi (AI) is a perennial herb found in Korea. Its ground parts are dried and used in food and traditional medicine for treating hepatitis, inflammation, cholelithiasis, and jaundice. In this study, the anti-obesity effects of single compounds isolated from AI extracts on adipose tissue were investigated. Results demonstrated that caffeoylquinic acid analogs strongly inhibited adipocyte differentiation from 3T3-L1 preadipocytes and reduced neutral lipids in differentiated adipocytes. Accordingly, lipid accumulation in adipocytes decreased, and lipid droplets became granulated. Caffeoylquinic acid analogs suppressed the expression of adipocyte differentiation marker genes, namely, Cebpa, Lep, and Fabp4, but it induced the expression of Ucp1, Ppargc1a, and Fgf21, which are browning biomarkers. Therefore, caffeoylquinic acid analogs from AI inhibited preadipocyte differentiation and induced adipose tissue browning, suggesting that these compounds could be promising therapeutic agents for obesity.

Keywords: Adipogenesis; Adipose tissue; Artemisia iwayomogi; Caffeoylquinic acid; Preadipocyte.

Fig. 1

Cytotoxic effects of AIE and purified compounds isolated from AIE. Cytotoxicity was represented as the percentage of cell viability compared with the DMSO control. (A) Cytotoxicity of AIE. Cytotoxicity of compounds isolated from AIE at 100 μM (B), 50, 25, and 12.5 μM (C). Data were expressed as mean ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the DMSO control

Fig. 2

Effects of chemical compound on preadipocyte differentiation. 3T3-L1 cells were cultured under differentiation for 2 days, transferred to maintenance media, and cultured for > 7 days before ORO staining. The cells were treated with each chemical compound after they were cultured with differentiation media on day 0. (A) Representative light microscopy images of 3T3-L1 cells with ORO staining (×400). (B) Quantification of intracellular lipid droplets in the cells treated with AIE, scopolin, hispidulin, jaceosidin, arteanoflavone, 1,3-di-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 3,5-di-O-CQA methyl ester. Data were expressed as mean ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the adipocyte control

Fig. 3

Effects of chemical compounds on lipid accumulation. 3T3-L1 cells were cultured under differentiation for 2 days, transferred to maintenance media, and cultured for > 7 days before ORO staining. The cells were treated with each chemical compound after they were cultured in the maintenance media on day 2. (A) Representative light microscopy images of 3T3-L1 cells with ORO staining (×400). (B) Quantification of intracellular lipid droplet. Data were expressed as mean ± SEM. *p < 0.05; **p < 0.01 compared with the adipocyte control

Fig. 4

Changes in the expression of adipogenesis-related genes and brown adipose tissue marker genes. (A) Cebpa, (B) Lep, (C) Fabp4, (D) Ucp1, (E) Cidea, (F) Ppargc1a, (G) Tfam, (H) Fgf21, and (I) Nrf1. mRNA expression was measured through quantitative real-time PCR. The signals were normalized to β-actin internal control. Data were expressed as mean ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with control