Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin

Abstract

The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the ratelimiting enzyme of cholesterol biosynthesis, 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, respectively); mucosal total and esterified cholesterol concentrations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of 125 I-labeled LDL to mucosal membranes. Feeding 2% sitosterol or 0.04% lovastatin for 1 week significantly ( P Ͻ 0.01) decreased the amounts of cholesterol absorbed per day ( Ϫ 85% and Ϫ 63%, respectively). In contrast, feeding 2% cholesterol for 1 week increased the amounts of absorbed cholesterol 27-fold, even though the percent absorption significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reductase activity ( P Ͻ 0.05) and receptor-mediated LDL binding ( P Ͻ 0.01), whereas lovastatin-and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimulation of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reductase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentrations of mucosal cholesterol, and only cholesterol-fed animals had increased mucosal esterified cholesterol concentrations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and receptor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum. -

Evaluation of the Hypocholesterolemic Effect and Phytochemical Screening of the Hydroethanolic Extract of Crataegus Aronia from Jordan

“…On the other hand, it was found that phytosterols, in general, act as cholesterol analogues. Phytosterols inhibit cholesterol absorption by competing with cholesterol for solubilization in the micelles prior to absorption [24]. Since ßsitosterol was also isolated from C. aronia in the present study, the observed effects on TC and LDL could be further substantiated by the presence of ß-sitosterol.…”

Analisis Penambatan Molekul Kandungan Kimia Tanaman Kelor (Moringa oleifera Lam.) Terhadap Target Molekuler Terapi Penyakit Kardiovaskular

“…Glukosinolat dari biji, daun, dan akar kelor telah diidentifikasi memiliki aktivitas sebagai antihipertensi. Ekstrak daun kelor mengandung β-sitosterol sebesar 90 mg/g, di mana β-sitosterol dilaproakm dapat mengurangi biosintesis kolesterol (Nguyen et al, 2001;Rajanandh and Kavitha, 2010 (Keiser et al, 2007;Nickel et al, 2014;Daina, Michielin and Zoete, 2017). Studi pendahuluan tersebut menghasilkan 5 protein yang diprediksi akan menjadi target kerja senyawa-senyawa dalam daun kelor, yaitu ACE, reseptor adrenergik β1 (ADRβ1), HMGCR, trombin, dan reseptor aldosteron.…”

“…Senyawa daucosterol (suatu β-sitosterol) memiliki kesesuaian model interaksi dengan ligan asli yang paling baik, sehingga senyawa ini diprediksi mampu menghambat enzim HMGCR. Hal ini sejalan dengan penelitian yang melaporkan bahwa sitosterol menghambat enzim HMGCR, walaupun belum sebanding lovastatin (Nguyen et al, 2001). Kuersetin juga menunjukkan model interaksi dan energi ikatan yang baik.…”