Defining the Cholesterol Lowering Mechanism of Bergamot (Citrus bergamia) Extract in HepG2 and Caco-2 Cells.
Defining the Cholesterol Lowering Mechanism of Bergamot (Citrus bergamia) Extract in HepG2 and Caco-2 Cells.
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DOI：
10.3390/nu13093156
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发表时间：
2021-09-10
期刊：
影响因子：
5.9
通讯作者：
Johnson JJ
中科院分区：
文献类型：
--
作者：
Huang Y;Tocmo R;Nauman MC;Haughan MA;Johnson JJ
佛手柑是一种原产于意大利南部的地中海柑橘类水果，据报道具有降低胆固醇的特性;然而，其作用机制尚不清楚。由于与3-羟基-3-甲基戊二酰-辅酶A还原酶（HMGCR）抑制剂的结构相似性，已经提出佛手柑中的酚类化合物也可以抑制HMGCR。他汀类药物因其降胆固醇特性而被广泛使用;然而，它们并不普遍耐受良好，这表明需要确定新的降胆固醇策略。在本研究中，我们研究了佛手柑果实提取物（BFE）及其主要成分（新圣草苷，柚皮苷，新橙皮苷，melitidin和brutieridin）调节HepG 2和Caco-2细胞胆固醇水平的能力。BFE在不断增加的浓度降低HepG 2细胞中的总胆固醇和游离胆固醇的水平。BFE及其组分不直接抑制HMGCR活性。然而，BFE和新橙皮苷降低HepG 2细胞中HMGCR的水平，表明新橙皮苷和BFE可能下调HMGCR的表达。在BFE和新橙皮苷处理的细胞中观察到AMP-激酶磷酸化的增加。在Caco-2细胞中，brutieridin表现出胆固醇摄取的显著降低，并降低了一种重要的胆固醇转运蛋白Niemann-Pick C1 Like 1的水平。总之，我们的数据表明佛手柑的降胆固醇活性与他汀类药物不同。我们推测BFE及其主要成分通过抑制胆固醇的合成和吸收来降低胆固醇。
Bergamot, a Mediterranean citrus fruit native to southern Italy, has been reported to have cholesterol-lowering properties; however, the mechanism of action is not well understood. Due to structural similarities with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors, it has been proposed that the phenolic compounds in bergamot may also inhibit HMGCR. Statins are widely used for their cholesterol-lowering properties; however, they are not universally well tolerated, suggesting there is a need to identify novel cholesterol-lowering strategies. In the present study, we investigated bergamot fruit extract (BFE) and its principal components (neoeriocitrin, naringin, neohesperidin, melitidin, and brutieridin) for their ability to regulate cholesterol levels in HepG2 and Caco-2 cells. BFE at increasing concentrations decreased the levels of total and free cholesterol in HepG2 cells. BFE and its constituents did not directly inhibit HMGCR activity. However, BFE and neohesperidin decreased HMGCR levels in HepG2 cells, suggesting that neohesperidin and BFE may downregulate HMGCR expression. An increase in AMP-kinase phosphorylation was observed in BFE and neohesperidin-treated cells. In Caco-2 cells, brutieridin exhibited a significant reduction in cholesterol uptake and decreased the level of Niemann-Pick C1 Like 1, an important cholesterol transporter. Taken together, our data suggest that the cholesterol-lowering activity of bergamot is distinct from statins. We hypothesize that BFE and its principal constituents lower cholesterol by inhibiting cholesterol synthesis and absorption.
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影响因子：
168.9
作者：
Mihaylova, B.;Emberson, J.;Blackwell, L.;Keech, A.;Simes, J.;Barnes, E. H.;Voysey, M.;Gray, A.;Collins, R.;Baigent, C.;de Lemos, J.;Braunwald, E.;Blazing, M.;Murphy, S.;Downs, J. R.;Gotto, A.;Clearfield, M.;Holdaas, H.;Gordon, D.;Davis, B.;Koren, M.;Dahlof, B.;Poulter, N.;Sever, P.;Knopp, R. H.;Fellstrom, B.;Holdaas, H.;Jardine, A.;Schmieder, R.;Zannad, F.;Goldbourt, U.;Kaplinsky, E.;Colhoun, H. M.;Betteridge, D. J.;Durrington, P. N.;Hitman, G. A.;Fuller, J.;Neil, A.;Wanner, C.;Krane, V.;Sacks, F.;Moye, L.;Pfeffer, M.;Hawkins, C. M.;Braunwald, E.;Kjekshus, J.;Wedel, H.;Wikstrand, J.;Barter, P.;Keech, A.;Tavazzi, L.;Maggioni, A.;Marchioli, R.;Tognoni, G.;Franzosi, M. G.;Maggioni, A.;Bloomfield, H.;Robins, S.;Collins, R.;Armitage, J.;Keech, A.;Parish, S.;Peto, R.;Sleight, P.;Pedersen, T. R.;Ridker, P. M.;Holman, R.;Meade, T.;Simes, J.;Keech, A.;MacMahon, S.;Marschner, I.;Tonkin, A.;Shaw, J.;Serruys, P. W.;Nakamura, H.;Knatterud, G.;Furberg, C.;Byington, R.;Macfarlane, P.;Cobbe, S.;Ford, I.;Murphy, M.;Blauw, G. J.;Packard, C.;Shepherd, J.;Kjekshus, J.;Pedersen, T.;Wilhelmsen, L.;Braunwald, E.;Cannon, C.;Murphy, S.;Collins, R.;Armitage, J.;Bowman, L.;Parish, S.;Peto, R.;Sleight, P.;Baigent, C.;Landray, M.;Collins, R.;La Rosa, J.;Rossouw, J.;Probstfield, J.;Shepherd, J.;Cobbe, S.;Macfarlane, P.;Ford, I.
通讯作者：
Ford, I.
影响因子：
5.1
作者：
Di Donna, Leonardo;De Luca, Giuseppina;Sindona, Giovanni
通讯作者：
Sindona, Giovanni
影响因子：
6.1
作者：
Miceli, Natalizia;Mondello, Maria R.;Trovato, Ada
通讯作者：
Trovato, Ada
影响因子：
3.7
作者：
Nekohashi M;Ogawa M;Ogihara T;Nakazawa K;Kato H;Misaka T;Abe K;Kobayashi S
通讯作者：
Kobayashi S
影响因子：
7.9
作者：
Giglio, Rosaria Vincenza;Patti, Angelo Maria;Rizzo, Manfredi
通讯作者：
Rizzo, Manfredi