探討黃連素在巨噬細胞對於抑制泡沫細胞形成及調控膽固醇細胞膜運載蛋白之機制

The Effects of Berberine on the Regulation of Cholesterol Membrane Transporters and Suppression of Foam Cell Formation in Macrophages

彭建中(Chien-Chung Peng)

指導教授 ： 呂平江 ； 徐松錕

國立清華大學/生命科學院/生物資訊與結構生物研究所/碩士(2009年)

摘要

ABSTRACT
Macrophage foam cell formation is the critical step in the development of atherosclerosis. Berberine, a botanical alkaloid, has been suggested to regulate lipid homeostasis by reducing serum cholesterol and triglyceride levels and to improve glucose metabolism. This study investigated the role of Berberine on lipid metabolism in macrophages. In THP-1-derived macrophages, Berberine suppressed lipid accumulation induced by oxidized-low density lipoprotein (ox-LDL). Berberine augmented the mRNA and protein expression of ATP-binding membrane cassette transport protein A1 (ABCA1) but did not alter the protein levels of ATP-binding membrane cassette transport protein G1 (ABCG1)、scavenger receptor B1 (SR-B1)、scavenger receptor A (SR-A) and clusters of differentiation 36 (CD36). Moreover, ABCA1 antibody or inhibitor abrogated the suppressive effect of Berberine on lipid accumulation. Finally, western blot analysis and confocal microscopy revealed that Berberine enhanced the nuclear translocation of liver X receptor-a but not its protein expression. These data suggest that Berberine inhibits the formation of foam cells by enhancing cholesterol efflux and could be effective for treatment of atherosclerosis.

關鍵字

黃連素 ； 粥狀動脈硬化 ； 泡沫細胞

參考文獻

Amin, A.H., Subbaiah, T.V., and Abbasi, K.M. (1969). Berberine sulfate: antimicrobial activity, bioassay, and mode of action. Can J Microbiol 15, 1067-1076.

Apfel, R., Benbrook, D., Lernhardt, E., Ortiz, M.A., Salbert, G., and Pfahl, M. (1994). A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily. Mol Cell Biol 14, 7025-7035.

Basha, S.A., Mishra, R.K., Jha, R.N., Pandey, V.B., and Singh, U.P. (2002). Effect of berberine and (+/-)-bicuculline isolated from Corydalis chaerophylla on spore germination of some fungi. Folia Microbiol (Praha) 47, 161-165.

Beyea, M.M., Heslop, C.L., Sawyez, C.G., Edwards, J.Y., Markle, J.G., Hegele, R.A., and Huff, M.W. (2007). Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol. J Biol Chem 282, 5207-5216.

Boisvert, W.A., Santiago, R., Curtiss, L.K., and Terkeltaub, R.A. (1998). A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 101, 353-363.