Synthesis of cholesterol analogues and comparison on their effect on plasma cholesterol with ß-Sitosterol.

The application of plant sterols in the treatment of hypercholesterolemia is promising. We hypothesize that plant sterols can reduce blood cholesterol because they have a side chain of at least three branches. Three cholesterol analogues were synthesized: CA0 (no side chain), CA3 (a 3­carbon chain with one branch), and CA14 (a 14­carbon side chain with two branches), and then compared their effect on blood cholesterol with that of ß-sitosterol. Structurally, ß-sitosterol has a 10­carbon side chain with three branches. Results demonstrated that ß-sitosterol could effectively reduce plasma total cholesterol (TC) by 20.3%, whereas CA0, CA3 and CA14 did not affect plasma TC in hypercholesterolemia hamsters. ß-Sitosterol was absent in the plasma and liver, indicating it was not absorbed. We concluded that ß-sitosterol with three branches had plasma TC-lowering activity. In contrast, cholesterol analogues with a side chain of two or fewer branches did not affect plasma cholesterol.

Mangiferin alleviates trimethylamine-N-oxide (TMAO)-induced atherogenesis and modulates gut microbiota in mice.

Trimethylamine-N-oxide (TMAO), originating from dietary trimethylamine-containing nutrients such as choline, has been recognized as a risk factor for atherosclerosis. Mangiferin is a bioactive xanthone initially extracted from mango (Mangifera indica). The present study aimed to investigate the effect of mangiferin on TMAO-induced atherogenesis in mice fed a high-choline diet. Female ApoE-/- mice were randomly divided into three groups and fed either a control diet, a high-choline diet with 1% free choline, or an experimental diet with 1% free choline plus 0.5% mangiferin for 15 weeks. Our results showed that a high-choline diet elevated plasma TMAO levels, accelerated atherogenesis, promoted cholesterol accumulation, and reduced the generation of short-chain fatty acids (SCFAs) by gut microbes. Mangiferin alleviated inflammation, and lowered plasma total cholesterol levels by facilitating the elimination of neutral and acidic sterols in feces, resulting in a 16.7-29.0% reduction in aortic atherosclerotic lesions. Notably, mangiferin could favorably remodel the composition of the gut microbiota by fostering the growth of the beneficial taxa Akkermansia, Parabacteroides, and Bifidobacteriaceae, while reducing the relative abundance of the pathogenic genus Helicobacter. This modulation led to a decrease in plasma lipopolysaccharide levels, enhanced the production of total SCFAs by gut microbes, and reduced susceptibility to atherosclerosis. In conclusion, mangiferin exhibited its ability to alleviate TMAO-induced atherosclerosis through its anti-inflammatory, cholesterol-lowering, and gut microbial modulatory activities.

Adverse effect of oxidized cholesterol exposure on colitis is mediated by modulation of gut microbiota.

Both cholesterol and oxidized cholesterol (OXC) are present in human diets. The incidence of inflammatory bowel diseases (IBDs) is increasing in the world. The present study was to investigate the mechanism by which OXC promotes colitis using C57BL/6 mice as a model. Results shown that more severe colitis was developed in OXC-treated mice with the administration of dextran sulfate sodium (DSS) in water. Direct effects of short-term OXC exposure on gut barrier or inflammation were not observed in healthy mice. However, OXC exposure could cause gut microbiota dysbiosis with a decrease in the relative abundance of short-train fatty acids (SCFAs)-producing bacteria (Lachnospiraceae_NK4A136_group and Blautia) and an increase in the abundance of some potential harmful bacteria (Bacteroides). OXC-induced symptoms of colitis were eliminated when mice were administered with antibiotic cocktails, indicating the promoting effect of OXC on DSS-induced colitis was mediated by its effect on gut microbiota. Moreover, bacteria-depleted mice colonized with gut microbiome from OXC-DSS-exposed mice exhibited a severe colitis, further proving the gut dysbiosis caused by OXC exposure was the culprit in exacerbating the colitis. It was concluded that dietary OXC exposure increased the susceptibility of colitis in mice by causing gut microbiota dysbiosis.

Physiological concentration of protocatechuic acid directly protects vascular endothelial function against inflammation in diabetes through Akt/eNOS pathway.

Background: Cardiovascular diseases (CVDs) have been the major cause of mortality in type 2 diabetes. However, new approaches are still warranted since current diabetic medications, which focus mainly on glycemic control, do not effectively lower cardiovascular mortality rate in diabetic patients. Protocatechuic acid (PCA) is a phenolic acid widely distributed in garlic, onion, cauliflower and other plant-based foods. Given the anti-oxidative effects of PCA in vitro, we hypothesized that PCA would also have direct beneficial effects on endothelial function in addition to the systemic effects on vascular health demonstrated by previous studies. Methods and results: Since IL-1ß is the major pathological contributor to endothelial dysfunction in diabetes, the anti-inflammatory effects of PCA specific on endothelial cells were further verified by the use of IL-1ß-induced inflammation model. Direct incubation of db/db mouse aortas with physiological concentration of PCA significantly ameliorated endothelium-dependent relaxation impairment, as well as reactive oxygen species overproduction mediated by diabetes. In addition to the well-studied anti-oxidative activity, PCA demonstrated strong anti-inflammatory effects by suppressing the pro-inflammatory cytokines MCP1, VCAM1 and ICAM1, as well as increasing the phosphorylation of eNOS and Akt in the inflammatory endothelial cell model induced by the key player in diabetic endothelial dysfunction IL-1ß. Upon blocking of Akt phosphorylation, p-eNOS/eNOS remained low and the inhibition of pro-inflammatory cytokines by PCA ceased. Conclusion: PCA exerts protection on vascular endothelial function against inflammation through Akt/eNOS pathway, suggesting daily acquisition of PCA may be encouraged for diabetic patients.

Effect of tea catechins on gut microbiota in high fat diet-induced obese mice.

BACKGROUND: Tea catechins have been shown to have beneficial effects on the alleviation of obesity, the prevention of diabetes, and the amelioration of metabolic syndrome. The purpose of the present work is to explore the underlying mechanisms linking the intestinal microbiota and anti-obesity benefits of green tea, oolong tea, and black tea catechins in C57BL/6J mice fed with a high-fat diet (HFD). RESULTS: The results indicated that, after the dietary intake of three tea catechins, obesity and low-grade inflammation were significantly alleviated. Hepatic steatosis was prevented, and this was accompanied by the upregulation of the mRNA and protein expressions of hepatic peroxisome proliferator-activated receptor α (PPARα). Metagenomic analysis of fecal samples suggested that the three tea catechins similarly changed the microbiota in terms of overall structure, composition, and protein functions by regulating the metabolites, facilitating the generation of short-chain fatty acids (SCFAs), and repressing lipopolysaccharides. CONCLUSION: The anti-obese properties of three tea catechins were partially mediated by their positive effect on gut microbiota, hepatic steatosis alleviation, and anti-inflammatory activity. © 2023 Society of Chemical Industry.

Dietary Oxidized Cholesterol Aggravates Chemically Induced Murine Colon Inflammation and Alters Gut Microbial Ecology.

Western diet with a higher intake of fat and cholesterol has been claimed as an intestinal inflammation trigger. Human diet contains both cholesterol and oxidized cholesterol. Oxidized cholesterol has been claimed to be associated with various inflammation diseases, but its effects on colitis and gut microbiome remain largely unknown. The present study was the first time to investigate the effect of the oxidized cholesterol on gut microbiota and dextran sodium sulfate-induced colitis using mice as a model. The results showed that oxidized cholesterol promoted colitis by exacerbating bleeding, body weight decrease, colon shortening, gut barrier damage, oxidative stress, and gut inflammation, whereas non-oxidized cholesterol had no effect. Meanwhile, oxidized cholesterol could adversely modulate the gut microbiota by increasing the relative abundance of pro-inflammatory bacteria (including Escherichia-Shigella and Bacteroides) and decreasing that of beneficial bacteria (Lachnospiraceae_NK4A136_group and Odoribacter). In addition, oxidized cholesterol significantly reduced the production of fecal short-chain fatty acids in colitis mice. It was concluded that oxidized cholesterol was a potential dietary factor of gut dysbiosis.

Effects of Thermally-Oxidized Frying Oils (Corn Oil and Lard) on Gut Microbiota in Hamsters.

Repeated reuse of frying oil raises health concerns due to the accumulation of oxidative products after each frying cycle. Gut microbiota is integral in lipid metabolism and immune regulation. The present study was designed to investigate the effects of thermally-oxidized corn oil and lard on gut microbiota in relation to atherosclerosis, inflammatory cytokines, and plasma lipids. Male Golden Syrian hamsters were randomly divided into four groups and fed one of four diets containing fresh corn oil (CF), oxidized corn oil (CO), fresh lard (LF), and oxidized lard (LO), for six weeks. CO and LO were prepared by deep-frying potatoes in corn oil or lard for seven days. Results indicated that oxidized oil and lard caused the loss of species diversity and richness of gut microbiota. Feeding CO and LO also reduced the body and adipose tissue weights, associated with genus Acetatifactor and Allobaculum. Plasma triacylglycerols significantly increased by 51% in the CO and 35% in the LO group compared with that in their CF and LF counterparts, respectively. CO could also affect the abundance of specific bacteria genera: Bacteroides, Barnesiella, Acetatifactor, Allobaculum, Clostridium_IV, Clostridium_XIVa, Coprococcus, Lactococcus, Paraprevotella, Parasutterella, and Oscillibacter. In addition, CO and LO could adversely remodel gut composition and affect intestinal production of short-chain fatty acids, pro-inflammatory biomarkers (LPS and IL-6), anti-inflammatory biomarker IL-10, and atherosclerotic progression. It was concluded that frying oil could adversely modulate the gut microbiota and exacerbate the atherosclerosis at least in a hypercholesterolemia hamster model.

Effects of hawthorn seed oil on plasma cholesterol and gut microbiota.

BACKGROUND: Hypercholesterolemia and gut microbiota dysbiosis are associated with the risk of cardiovascular diseases. Hawthorn fruits has shown to be cardioprotective and hypocholesterolemic. However, no studies to date have studied the biological activity of hawthorn seed oil (HSO). The present study was to investigate if HSO could favourably reduce plasma cholesterol and modulate gut microbiota in hypercholesterolemia hamsters. METHODS: Golden Syrian hamsters (age, 8 weeks) were randomly divided into five groups (n = 8, each) and fed one of the following five diets, namely a non-cholesterol diet, a high cholesterol diet containing 0.15% cholesterol (HCD); a HCD diet with addition of 4.75% HSO (LHSO), a HCD diet with addition of 9.5% HSO (HHSO), a HCD diet with addition of 0.50% cholestyramine as positive control diet. After 6-week dietary intervention, plasma lipids, inflammatory markers, atherosclerosis plaque, hepatic and fecal lipids were quantified. Microbiota in fresh feces were analysed by sequencing 16S rRNA genes, while RT-PCR and Western blot analyses were employed to quantify the expression of genes involved in cholesterol homeostasis. RESULTS: HSO at a dose of 9.5% HSO could decrease plasma cholesterol and non-HDL-cholesterol by 15%. Additionally, both HSO experimental groups also suppressed mRNA of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG-CoA-R). Supplementation of HSO at 4.75% could significantly increase the excretion of fecal acidic sterols, accompanied by elevation of short-chain fatty acid levels in feces. The analyses of gut microbiome indicated that HSO supplementation could selectively alter the genera abundance of gut bacteria that were correlated with cholesterol metabolism including unclassified_f__Christensenellaceae, Ruminococcaceae_NK4A214_ group, norank_o_Gastranaerophilales, Faecalibaculum, Peptococcus, norank_f__Clostridiales_vadinBB60_group and Ruminococcus_2. CONCLUSIONS: HSO supplementation was able to decrease plasma cholesterol by favourably modulating gut microbiota composition and gut-derived metabolites associated with cholesterol regulation.

Peony seed oil decreases plasma cholesterol and favorably modulates gut microbiota in hypercholesterolemic hamsters.

PURPOSE: Peony (Paeonia spp.) seed oil (PSO) contains a high amount of α-linolenic acid. The effects of PSO on hypercholesterolemia and gut microbiota remains unclear. The present study was to investigate effects of PSO supplementation on cholesterol metabolism and modulation of the gut microbiota. METHODS: Male Golden Syrian hamsters (n = 40) were randomly divided into five groups (n = 8, each) fed one of the following diets namely low-cholesterol diet (LCD); high cholesterol diet (HCD); HCD with PSO substituting 50% lard (LPSO), PSO substituting 100% lard (HPSO) and HCD with addition of 0.5% cholestyramine (PCD), respectively, for 6 weeks. RESULTS: PSO supplementation dose-dependently reduced plasma total cholesterol (TC) by 9-14%, non-high-density lipoprotein cholesterol (non-HDL-C) by 7-18% and triacylglycerols (TG) by 14-34% (p < 0.05). In addition, feeding PSO diets reduced the formation of plaque lesions by 49-61% and hepatic lipids by 9-19% compared with feeding HCD diet (p < 0.01). PSO also altered relative genus abundance of unclassified_f__Coriobacteriaceae, unclassified_f__Erysipelotrichaceae, Peptococcus, unclassified_f__Ruminococcaceae, norank_o__Mollicutes_RF9 and Christensenellaceae_R-7_group. CONCLUSIONS: It was concluded that PSO was effective in reducing plasma cholesterol and hepatic lipids and favorably modulating gut microbiota associated with cholesterol metabolism.

Cholesterol-lowering activity of protocatechuic acid is mediated by increasing the excretion of bile acids and modulating gut microbiota and producing short-chain fatty acids.

The present study aimed to investigate the effects of protocatechuic acid (PCA) on plasma lipid profiles and associated mechanisms with a focus on reshaping gut microbiota. Twenty-four male hamsters were randomly divided into three groups receiving a high-cholesterol diet (HCD) and two HCD diets containing 0.5% (PL) and 1% (PH) PCA, respectively. Feeding PL and PH diets for six weeks significantly reduced plasma total cholesterol by 18% and 24%, respectively. PL and PH diets also significantly lowered plasma non-HDL cholesterol by 37% and 44%, respectively. This was accompanied by an increase in fecal short-chain fatty acids (SCFAs) and fecal bile acids with up-regulation on gene of cholesterol 7α-hydroxylase and down-regulation of 3-hydroxy-3-methylglutaryl-CoA reductase in the liver. Dietary PCA supplementation decreased hepatic lipid accumulation, whereas it increased fecal excretion of lipids. The 16S rRNA analysis found that dietary PCA significantly reduced the ratio of Firmicutes to Bacteroidetes and increased the relative abundance of Bacteroidales S24-7, whereas it reduced the abundance of Lactobacillaceae. It was concluded that dietary PCA favorably modulated plasma lipid profiles and prevented the accumulation of hepatic cholesterol and lipid disposition. Such effect was mediated at least partially by increasing gut production of SCFAs and fecal excretion of bile acids via modulating the gut microbiome.

Rutin and Quercetin Decrease Cholesterol in HepG2 Cells but Not Plasma Cholesterol in Hamsters by Oral Administration.

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.

Hawthorn fruit extract reduced trimethylamine-N-oxide (TMAO)-exacerbated atherogenesis in mice via anti-inflammation and anti-oxidation.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is an independent risk factor for atherosclerosis. Consumption of hawthorn fruit is believed to be cardio-protective, yet whether it is able to suppress the TMAO-induced atherosclerosis remains unexplored. The present study was to investigate the effects of hawthorn fruit extract (HFE) on TMAO-exacerbated atherogenesis. METHODS: Five groups of male Apolipoprotein E knock-out (ApoE-/-) mice were fed a low-fat diet (LFD), a Western high-fat diet (WD), or one of the three WDs containing 0.2% TMAO (WD + TMAO), 0.2% TMAO plus 1% HFE (WD + TMAO + L-HFE), or 0.2% TMAO plus 2% HFE (WD + TMAO + H-HFE), respectively. After 12-weeks of intervention, plasma levels of TMAO, lipid profile, inflammatory biomarkers, and antioxidant enzyme activities were measured. Atherosclerotic lesions in the thoracic aorta and aortic sinus were evaluated. The sterols and fatty acids in the liver and feces were extracted and measured. Hepatic expressions of inflammatory biomarkers and antioxidant enzymes were analyzed. RESULTS: Dietary TMAO accelerated atherogenesis, exacerbated inflammation, and reduced antioxidant capacities in the plasma and the liver. TMAO promoted hepatic cholesterol accumulation by inhibiting fecal excretion of acidic sterols. HFE could dose-dependently reduce the TMAO-aggravated atherosclerosis and inflammation. HFE was also able to reverse the TMAO-induced reduction in antioxidant capacity by up-regulating the expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase 3 (GSH-Px3), and catalase (CAT) in the liver. Moreover, the hepatic cholesterol content was lowered by HFE via enhanced fecal excretion of neutral and acidic sterols. CONCLUSIONS: The present results indicated that HFE was able to reduce the TMAO-exacerbated atherogenesis by attenuating inflammation and improving antioxidant capacity at least in mice.

Blueberry and cranberry anthocyanin extracts reduce bodyweight and modulate gut microbiota in C57BL/6 J mice fed with a high-fat diet.

PURPOSE: Blueberry and cranberry are rich in anthocyanins. The present study was to investigate the effects of anthocyanin extracts from blueberry and cranberry on body weight and gut microbiota. METHODS: C57BL/6 J Mice were divided into six groups (n = 9 each) fed one of six diets namely low-fat diet (LFD), high-fat diet (HFD), HFD with the addition of 1% blueberry extract (BL), 2% blueberry extract (BH), 1% cranberry extract (CL), and 2% cranberry extract (CH), respectively. RESULTS: Feeding BL and BH diets significantly decreased body weight gain by 20-23%, total adipose tissue weight by 18-20%, and total liver lipids by 16-18% compared with feeding HFD. Feeding CH diet but not CL diet reduced the body weight by 27%, accompanied by a significant reduction of total plasma cholesterol by 25% and tumor necrosis factor alpha (TNF-α) by 38%. The metagenomic analysis showed that the supplementation of blueberry and cranberry anthocyanin extracts reduced plasma lipopolysaccharide concentration, accompanied by a reduction in the relative abundance of Rikenella and Rikenellaceae. Dietary supplementation of berry anthocyanin extracts promoted the growth of Lachnoclostridium, Roseburia, and Clostridium_innocuum_group in genus level, leading to a greater production of fecal short-chain fatty acids (SCFA). CONCLUSIONS: It was concluded that both berry anthocyanins could manage the body weight and favorably modulate the gut microbiota at least in mice.

Ursolic acid alleviates hypercholesterolemia and modulates the gut microbiota in hamsters.

Ursolic acid (UA) is a triterpenoid acid widely abundant in fruits and vegetables such as apple, blueberry and cranberry. The present study was carried out to investigate the effect of UA supplementation in diet on blood cholesterol, intestinal cholesterol absorption and gut microbiota in hypercholesterolemic hamsters. A total of thirty-two hamsters were randomly assigned to four groups and given a non-cholesterol diet (NCD), a high-cholesterol diet containing 0.1% cholesterol (HCD), an HCD diet containing 0.2% UA (UAL), or an HCD diet containing 0.4% UA (UAH) for 6 weeks. Results showed that UA supplementation reduced plasma cholesterol by 15-16% and inhibited intestinal cholesterol absorption by 2.6-9.2%. The in vitro micellar cholesterol solubility experiment clearly demonstrated that UA could displace 40% cholesterol from micelles. In addition, UA decreased the ratio of Firmicutes to Bacteroidetes, whereas it enhanced the growth of short chain fatty acid (SCFA)-producing bacteria in the intestine. In conclusion, UA possessed a cholesterol-lowering activity and could favorably modulate the gut microbiota.

Vinegars but not acetic acid are effective in reducing plasma cholesterol in hamsters fed a high-cholesterol diet.

The present study compares the effect of two types of vinegars, Balsamic vinegar of Modena (BV) and Chinese Shanxi vinegar (SV), with acetic acid on plasma cholesterol using hamsters as a model. Hamsters (n = 40) were divided into five groups (n = 8 each) with two control groups being fed a low-cholesterol diet (LCD) or a high-cholesterol diet containing 0.2% cholesterol (HCD). The three experimental groups were given a HCD diet and gavaged with 8 ml of BV, SV, and acetic acid solution (AC) per kg body weight, respectively. Acetic acid in BV, SV, and AC solutions was adjusted with water to be 20 mg ml-1. The whole experiment lasted for 9 weeks. Plasma total cholesterol (TC) in BV and SV groups but not in the AC group was reduced by 17% and 20%, respectively, compared with that in HCD hamsters. BV and SV significantly reduced cholesterol in the liver and increased the fecal excretion of neutral sterols and bile acids. Real-time PCR analysis demonstrated that BV and SV significantly up-regulated the mRNA of cholesterol 7 alpha-hydroxylase (CYP7A1) in the liver. In conclusion, BV and SV but not AC were effective in reducing plasma TC and non-HDL-C concentrations at least in hypercholesterolemic hamsters.

Wild Melon Seed Oil Reduces Plasma Cholesterol and Modulates Gut Microbiota in Hypercholesterolemic Hamsters.

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_vadinBB60_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.

Fish Oil Is More Potent than Flaxseed Oil in Modulating Gut Microbiota and Reducing Trimethylamine-N-oxide-Exacerbated Atherogenesis.

Trimethylamine-N-oxide (TMAO) is a risk factor for atherosclerosis. We compared the potency of fish oil with flaxseed oil in reducing TMAO-exacerbated atherogenesis. Five groups of ApoE-/- mice were given one of five diets, namely, a low-fat diet, a Western high fat diet (WD), a WD plus 0.2% TMAO, and two WDs containing 0.2% TMAO with 50% lard being replaced by flaxseed oil or fish oil. TMAO accelerated atherosclerosis and disturbed cholesterol homeostasis. Compared with flaxseed oil, fish oil was more effective in inhibiting TMAO-induced atherogenesis by lowering plasma cholesterol and inflammatory cytokines. Both oils could reverse TMAO-induced decrease in fecal acidic sterols. Fish oil promoted fecal output of neutral sterols and downregulated hepatic cholesterol biosynthesis. Fish oil was more effective than flaxseed oil in promoting the growth of short-chain fatty acid-producing bacteria and lowering microbial generation of lipopolysaccharide. In conclusion, fish oil is more potent than flaxseed oil to ameliorate TMAO-exacerbated atherogenesis.

Plasma Cholesterol-Lowering Activity of Soybean Germ Phytosterols.

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.

Isoflavones enhance the plasma cholesterol-lowering activity of 7S protein in hypercholesterolemic hamsters.

Previous studies have shown that 7S protein is the active ingredient responsible for the plasma cholesterol-lowering activity of soybean. It is hypothesized that isoflavones in soybean could enhance the blood cholesterol-lowering activity of 7S protein. Forty-eight hamsters were divided into six groups and fed a non-cholesterol diet or one of the five high-cholesterol diets containing 12.1% 7S protein with 0-15.62 mg g-1 isoflavones. The results showed that addition of isoflavones in diets dose-dependently enhanced the plasma total cholesterol-lowering activity of 7S protein. Addition of isoflavones in 7S protein-based diets significantly reduced hepatic cholesterol accumulation by 12.6-26.1%, compared with the high cholesterol control diet. Isoflavones could also facilitate excretion of neutral sterols in a dose-dependent manner. Supplementation of isoflavones in diets favourably modulated mRNA expression and the protein mass of HMG-CoA reductase. It was concluded that the enhancing effect of isoflavones on the blood cholesterol-lowering activity of 7S protein was mediated by inhibiting the cholesterol absorption and de novo cholesterol synthesis in hypercholesterolemic hamsters.

Sea buckthorn seed oil reduces blood cholesterol and modulates gut microbiota.

Sea buckthorn seed oil (SBSO) has been used as a functional food in the prevention of heart diseases. The present study investigates the effects of SBSO on blood cholesterol and the gut microbiota in hypercholesterolemia hamsters. Four groups of hamsters (n = 8 each) were given one of four diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD) containing 0.1% cholesterol, and an HCD diet with sea buckthorn seed oil replacing 50% lard (SL) or replacing 100% lard (SH). Feeding SL and SH diets could reduce blood total cholesterol by 20-22%. This was accompanied by the down-regulation of the gene expression of acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporter8 (ABCG8). SBSO supplementation also increased the production of intestinal short-chain fatty acids and fecal outputs of neutral sterols. Metagenomic analysis demonstrated that feeding SL and SH diets could favorably modulate the relative abundance of Bacteroidales_S24-7_group, Ruminococcaceae, and Eubacteriaceae. It was therefore concluded that SBSO was effective in reducing blood cholesterol in hypercholesterolemic hamsters via increasing intestinal cholesterol excretion and promoting the growth of SCFA-producing bacteria.