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Wild melon ( Cucumis melo var. agrestis) seed oil (CO) contains 71.3% polyunsaturated fatty acids. The present study investigated the effects of CO on blood cholesterol and gut microbiota. Hamsters ( n = 32) were randomly divided into four groups and given one of four diets, namely noncholesterol diet (NCD), high-cholesterol diet containing 0.1% cholesterol (HCD), HCD containing 4.75% CO (COL), and HCD containing 9.5% CO (COH) for 6 weeks. CO supplementation at 9.5% in the diet reduced plasma cholesterol by 24% and enhanced the excretion of fecal bile acids by 150%. CO supplementation upregulated the gene expression of hepatic cholesterol 7α-hydroxylase (CYP7A1). In addition, supplementation of CO in the diet remarkably increased the production of fecal short-chain fatty acids and favorably altered the relative abundances of Eubacteriaceae , Clostridiales_vadinBB 60_group, Ruminococcaceae , Streptococcaceae , and Desulfovibrionaceae at a family level. It was concluded that CO could reduce plasma cholesterol via promoting the excretion of fecal acidic sterols and modulating gut microbiota.

Soybean germ phytosterols (SGP) largely exist in soybean germ oil. Our previous study demonstrated that soybean germ oil was effective in reducing plasma cholesterol. However, it remains unknown if its phytosterols are the active ingredients responsible for the plasma cholesterol-lowering activity. The present study aimed to test the effect of SGP on plasma cholesterol and to investigate its associated underlying mechanisms using hamsters as animal model. Male hamsters ( n = 40) were randomly divided into five groups ( n = 8/group) and fed one of the five diets: a non-cholesterol diet (NCD), a high cholesterol diet (HCD), a HCD diet containing 0.5% cholestyramine (PC), and two HCD diets containing 0.1% (LP) and 0.2% (HP) SGP, respectively, for six weeks. Results showed that SPG reduced plasma cholesterol level in a dose-dependent manner, whereas it dose-dependently increased the excretion of both fecal neutral and acidic sterols. SGP was also effective in displacing cholesterol from micelles. It was concluded that SGP possessed hypocholesterolemic activity, likely by inhibiting cholesterol absorption in the intestine and promoting fecal sterol excretion.

Health benefits of soybean germ oil have not yet been fully explored. The present study examined the blood cholesterol-lowering activity of soybean germ oil and the underlying mechanisms in hypercholesterolemic hamsters. Forty hamsters were randomly assigned into five groups and fed a non-cholesterol diet, a high cholesterol diet and one of three high cholesterol diets containing 0.50% cholestyramine, 4.75% soybean germ oil, and 9.50% soybean germ oil, respectively, for 6 weeks. The result showed that soybean germ oil significantly decreased plasma cholesterol by 18.5-31.5%, which was accompanied by 28.3-62.7% increase in excretion of fecal neutral sterols and bile acids. The effect was mediated by down-regulation of intestinal Niemann-Pick C1-like 1 protein (NPC1L1) and up-regulation of liver cholesterol-7α-hydroxylase (CYP7A1). We concluded that soybean germ oil favorably modulated the blood cholesterol concentration by inhibiting cholesterol absorption through inhibiting gene expression of NPC1L1 and by enhancing bile acid excretion via promoting gene expression of CYP7A1.

Rice bran oil (RBO) possesses a plasma cholesterol-lowering activity, while effect of wheat bran oil (WBO) on plasma cholesterol remains unknown. The present study compared the cholesterol-lowering activity of WBO with that of RBO in hamsters. Fifty-four male hamsters were divided into seven groups fed either a noncholesterol diet (NCD) or one of six high-cholesterol diets, namely HCD diet (0.2% cholesterol +9.5% lard), HCD+C diet (0.2% cholesterol +9.5% lard +0.5% cholestyramine), WL diet (0.2% cholesterol +4.8% Lard +4.8% WBO), WH diet (0.2% cholesterol +9.5% WBO), RL diet (0.2% cholesterol +4.8% Lard +4.8% RBO), and RH diet (0.2% cholesterol +9.5% RBO). Plasma total cholesterol (TC) in HCD group was 327.4 ± 31.8 mg/dL, while plasma TC in two WBO and two RBO groups was 242.2 ± 20.8, 243.1 ± 31.7, 257.1 ± 16.3, and 243.4 ± 46.0 mg/dL, respectively, leading to a decrease in plasma TC by 22-26% ( P < 0.01). No significant difference in cholesterol-lowering potency was seen between WBO and RBO. Plasma cholesterol-lowering activity of WBO and RBO was accompanied by down-regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase and fatty acid synthase, while up-regulation of cholesterol-7α-hydroxylase. WL, WH, RL, and RH diets increased the fecal excretion of total neutral sterols by 72.8%, 106.9%, 5.4%, and 36.8% ( P < 0.01) respectively. Results indicated WBO and RBO could inhibit cholesterol absorption via down-regulation of intestinal Niemann-Pick C1 like 1 protein, acyl CoA:cholesterol acyltransferase 2, and ATP binding cassette transporter 5. In summary, WBO was equally effective as RBO in decreasing plasma cholesterol in hypercholesterolemia hamsters.

Background: Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown., Hypothesis: The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion., Methods: Forty-four hamsters were randomly divided into five groups and fed one of the five diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD), a HCD diet supplemented with a low dose of 1% CrA (CL), a HCD diet supplemented with a high dose of 2% CrA (CH), and a HCD diet supplemented with 0.5% cholestyramine as a positive control drug (P-CTL), respectively, for six weeks. Plasma lipoprotein cholesterol was quantified using the enzymatic kits, while the gene expressions of transporters, enzymes and receptors involved in cholesterol absorption and metabolism were quantified using the quantitative RT-PCR. Fecal sterols were quantified using gas chromatography (GC)., Results: Plasma total cholesterol and aorta atherosclerotic plaque decreased dose-dependently with the increasing amounts of CrA added into diets. This was accompanied by a dose-dependent increase in excretion of both neutral and acidic sterols. CrA had no effect on the mRNA levels of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl CoA:cholesterol acyltransferase2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5) as well as hepatic cholesterol-7α-hydroxylase (CYP7A1), 3-Hydroxy-3-methylglutaryl reductase (HMG-CoA-R), sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDL-R), and Liver X receptor alpha (LXRα)., Conclusion: CrA as an herbal medicine could favorably modify the lipoprotein profile in hamsters fed a high cholesterol diet by enhancing excretion of fecal neutral and acidic sterols, most likely not mediated by interaction with genes of transporters, enzymes and proteins involved in cholesterol absorption and metabolism., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Sesame seed is rich in sesamin. The present study was to (i) investigate the plasma cholesterol-lowering activity of dietary sesamin and (ii) examine the interaction of dietary sesamin with the gene expression of sterol transporters, enzymes, receptors, and proteins involved in cholesterol metabolism. Thirty hamsters were divided into three groups fed the control diet (CON) or one of two experimental diets containing 0.2% (SL) and 0.5% (SH) sesamin, respectively, for 6 weeks. Plasma total cholesterol (TC) levels in hamsters given the CON, SL, and SH diets were 6.62 ± 0.40, 5.32 ± 0.40, and 5.00 ± 0.44 mmol/L, respectively, indicating dietary sesamin could reduce plasma TC in a dose-dependent manner. Similarly, the excretion of total fecal neutral sterols was dose-dependently increased with the amounts of sesamin in diets (CON, 2.65 ± 0.57; SL, 4.30 ± 0.65; and SH, 5.84 ± 1.27 μmol/day). Addition of sesamin into diets was associated with down-regulation of mRNA of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporters subfamily G members 5 and 8 (ABCG5 and ABCG8). Results also showed that dietary sesamin could up-regulate hepatic cholesterol-7α-hydroxylase (CYP7A1), whereas it down-regulated hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and liver X receptor alpha (LXRα). It was concluded that the cholesterol-lowering activity of sesamin was mediated by promoting the fecal excretion of sterols and modulating the genes involved in cholesterol absorption and metabolism.

The present study examined the cholesterol-lowering activity of sterol extract (SE) derived from alga Schizochytrium sp. and its interaction with gene expression of transporters, receptors, and enzymes involved in cholesterol absorption and metabolism. GC-MS analyses found that SE was a mixture of various sterols including lathosterol, ergosterol, stigmasterol, 24-ethylcholesta-5,7,22-trienol, stigmasta-7,24(24(1))-dien-3β-ol, and cholesterol. Results showed that SE at doses of 0.06 and 0.30 g/kg diet were able to decrease plasma cholesterol concentration by 19.5 and 34%, respectively, compared with the control, in hamsters maintained on a 0.1% high-cholesterol diet. SE at a dose of 0.30 g/kg diet was as effective as β-sitosterol in reducing plasma total cholesterol (TC). SE-induced reduction in plasma TC was accompanied by down-regulation of intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2) and hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and up-regulation of hepatic low-density lipoprotein (LDL) receptor. Addition of SE to the diet increased the excretion of total fecal sterols. It was concluded that SE possessed the same cholesterol-lowering activity as β-sitosterol and the underlying mechanisms were mediated by increasing sterol excretion and decreasing cholesterol absorption and synthesis.

This study was to examine the effect of free cholesterol (C) and individual cholesteryl ester (CE) species, namely cholesteryl palmitate (CP), cholesteryl stearate (CS), cholesteryl oleate (CO), and cholesteryl linoleate (CL) on plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triacylglycerols (TG) in hamsters. Results showed that addition of dietary CE species into diet at 0.1% differently raised plasma TC concentrations, with CO elevating plasma TC to 331 mg/dL, while CS raised plasma TC only to 220 mg/dL. It was found that CS was a poor substrate of pancreatic cholesterol esterase, while CO was a good substrate. The fecal analysis showed CS-fed hamsters had the highest fecal cholesterol concentration, while RT-PCR analysis found CS feeding was associated with down-regulations of intestinal Niemann-Pick C1 like 1 (NPC1L1) and acyl-CoA: cholesterol acyltransferase 2 (ACAT2) as well as microsomal triacylglycerol transport protein (MTP). It was therefore concluded that the plasma cholesterol-raising activity of CE species was partially governed by their hydrolysis rates in the intestine, and the relative low raising activity associated with CS was mediated by down-regulation of intestinal NPC1L1, ACAT2, and MTP.

The present study examined the cholesterol-lowering activity of algal powder (AP), algal lipids (AL), and algal residue (AR) and their interaction with genes of transporters, receptors, and enzymes involved in cholesterol absorption and metabolism. In this experiment, 48 hamsters were fed either control diet or one of the three experimental diets containing 2% AP, 1.0% AL, or 1.0% AR for 6 weeks. Plasma total cholesterol (TC) and non-high-density-lipoprotein-cholesterol (non-HDL-C) were significantly decreased in the AP and AL groups but not in the AR group compared with those in the control hamsters. It was found that the cholesterol-lowering activity of AP and AL was associated with down-regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, low-density lipoprotein receptor (LDLR), and intestinal Niemann-Pick C1-like 1 (NPC1L1) transporter. It was concluded that the alga possessed the cholesterol-lowering activity and its lipids were the active ingredients. The mechanisms underlying the cholesterol-lowering activity of algae were mediated most likely by increasing the sterol excretion and decreasing the cholesterol absorption and synthesis.

Ursolic acid (UA) is a natural triterpene carboxylic acid with an underlying anti-hyperlipidemia effect. This study examined the mechanism of interactions of UA with cholesterol esterase (CEase), pancreatic lipase (PL), and micellar cholesterol solubility in vitro. The half-maximal inhibitory concentration (IC50) of CEase, PL, and micellar cholesterol solubility was determined to be 0.07 ± 0.01 mg/mL, 1.81 ± 0.13 mg/mL, and 1.73 ± 0.08 mg/mL, respectively. Multispectral combination revealed that UA changed the secondary structure and quenched the intrinsic fluorescence by static quenching of the two enzymes. The interactions were exothermic reaction as determined by enthalpy. Furthermore, molecular docking confirmed that UA was bound to amino acids of two enzymes at active site through hydrophobic interaction and van der Waals forces. Molecular dynamics (MD) simulation found that CEase and PL rearranged with UA to form stable complexes. The strong inhibition effect of CEase and PL mediated by UA might provide additional insight into understanding the role of UA in the hypolipidemic effect. [ABSTRACT FROM AUTHOR]

Abstract: The present study examined the cholesterol-lowering activity of omega-3 docosapentaenoic acid (DPA n-3), omega-6 docosapentaenoic acid (DPA n-6) and docosahexaenoic acid (DHA), and their interaction with gene expression of transporters, receptors and enzymes involved in cholesterol absorption and metabolism as well as their effect on aortic function. Forty hamsters were fed either the control diet containing 0.4% stearic acid or one of the three experimental diets containing 0.4% DPA n-3, 0.4% DPA n-6 and 0.4% DHA. Results showed that supplementation of these three fatty acids reduced plasma total cholesterol (TC) and non high-density-lipoprotein cholesterol (non-HDL-C) by 29–33% and 29–50%, respectively, compared with the control. The reduction in TC and non-HDL-C was accompanied by down-regulation of hepatic SREBP-2 and HMG-CoA reductase. Aorta from DPA n-3 and DHA groups was found to have significantly lesser tension and relax better than that from the control and DPA n-6 hamsters, largely mediated by their inhibition on the gene expression of cycloxygense-2 (COX-2). It was concluded that all three fatty acids were beneficial in improving lipoprotein profile with DPA n-3 and DHA having better effect on aortic function. [Copyright &y& Elsevier]

Abstract: We investigated the relative hypocholesterolemic activity of linoleic acid (LA), conjugated linoleic acid (CLA), α-linolenic acid (LN) and conjugated linolenic acid (CLN) in hamsters. Five groups of hamsters (n =10 each) were fed either the control diet or one of the four fatty acids-supplemented diets for 6 weeks. Results demonstrated that the four octadecaenoic acids decreased plasma cholesterol differently, with CLA being the most effective. Western blotting and RT-PCR analysis demonstrated that the four octadecaenoic acids had no effect on sterol regulatory element binding protein-2 (SREBP-2), liver X receptor (LXR), 3-hydroxy-3-methylglutary-CoA reductase (HMGR), LDL receptor (LDLR), and cholesterol-7α-hydroxylase (CYP7A1). However, the four octadecaenoic acids increased the excretion of fecal neutral sterols with CLA being most effective followed by LN, LA and CLN, suggesting they all differentially affect cholesterol absorption. Dietary CLA was associated with the least intestinal acyl coenzyme A: cholesterol acyltransferase (ACAT) activity followed by LN, LA and CLN in a decreasing trend. Since esterification of cholesterol is catalyzed by intestinal ACAT, and is a rate-limiting step in cholesterol absorption, it was concluded that the varying effects of CLA, LN, LA and CLN on blood cholesterol were mediated, at least in part, by their inhibition on intestinal ACAT activity. [Copyright &y& Elsevier]