Fecal Total Cholesterol Research Articles

Heat-killed Lactiplantibacillus plantarum Shinshu N-07 exerts antiobesity effects in western diet-induced obese mice.

The aim of this study was to evaluate the antiobesity effects of heat-killed Lactiplantibacillus plantarum Shinshu N-07 (N-07) isolated from fermented Brassica rapa L. Male mice were divided into three groups (n=10/group); normal diet, western diet (WD), or WD+N-07 (N-07) group and administered each diet for 56 days. The N-07 group showed significant suppression of body weight gain and epididymal fat, perirenal fat, and liver weights compared with the WD group. Higher levels of fecal total cholesterol, triglyceride (TG), and free fatty acid (FFA) were observed in the N-07 group than in the WD group. The mRNA expression of the cholesterol transporter ATP-binding cassette transporter G5 (ABCG5) was significantly increased in the small intestine of N-07-fed mice compared with WD-fed mice. Moreover, N-07 supplementation significantly increased the mRNA expression of ABCG5 and ABCG8 in Caco-2 cells. Furthermore, the TG- and FFA-removal ability of N-07 was confirmed to evaluate its soybean oil- and oleic acid-binding capacities in in vitro experiments. The antiobesity effects of N-07 might be due to its ability to promote lipid excretion by regulating cholesterol transporter expression and lipid-binding ability.

Dan-shen Yin promotes bile acid metabolism and excretion to prevent atherosclerosis via activating FXR/BSEP signaling pathway

Ethnopharmacological relevanceDan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. Aim of the studyThis study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. Materials and methodsThe comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE−/− mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. ResultsA total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE−/− mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. ConclusionThis study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis.

Cow's Milk Allergy May Induce Lipid Metabolism Disorder in BALB/c Mice via Exosomes.

Allergic diseases and lipid-metabolism-disorder-derived diseases are both significant public health issues. Recent studies have shown that exosomes are associated with the course of allergic diseases and are involved in lipid metabolism. In this study, exosomes derived from cow's milk allergic (CMA) mice medially loaded lesser proteins favoring cholesterol metabolism. The levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the serum were increased in the CMA mice, and hepatic lipid deposition was observed in the liver, but these phenomena were improved by inhibiting the exosome release. Specifically, the higher expression of the sterol regulatory element binding factor 2 (SREBP2) protein and HMGCR gene in the liver of CMA mice indicated an increase in cholesterol synthesis. NPC1L1 was also highly expressed in the small intestine of CMA mice, and fecal TC level was decreased, suggesting that the reabsorption of cholesterol was elevated. The biosynthesis of cholesterol, the reverse cholesterol transport (RCT) process, and the synthesis of bile acid in the liver were improved by inhibiting exosome release, as well as the reabsorption of cholesterol in the small intestine. This study has for the first time demonstrated the lipid metabolism disorder caused by CMA, especially the important role of exosomes in food allergies and lipid metabolism.

Immature carob pods extract and its fractions prevent lipid metabolism disorders and lipoprotein-rich plasma oxidation in mice: A phytochemical and pharmacological study

Ethnopharmacological relevance: In Morocco carob fruits are used traditionally to treat hypercholesterolemia, diabetes and related diseases. Aims: This study was designed to evaluate the hypolipidemic activity of Ceratonia siliqua green pods extract and its fractions in Triton WR-1339 and high fat/cholesterol diet (HFCD) induced hyperlipidemia mice, as well as their ability to prevent lipoproteins oxidation in vitro. Materials and methods: High performance liquid chromatography (HPLC) analysis was used to determine the phenolic composition of the immature carob pods extract (HWCE). Antioxidant activities were evaluated using the DPPH radical scavenging test as well as MDA measurement in oxidized lipoprotein rich plasma. Plasma lipids, glucose and biliary total cholesterol, as well as lipids level in liver and feces, were analyzed. The acute oral toxicity was performed in mice single dosed with the HWCE at 2000 and 5000 mg/kg body weight. Results: HPLC analysis shows that gallic acid is the main phenolic compound in the HWCE. The acute oral toxicity assessment revealed that the HWCE is not toxic (LD50 is greater than 5000 mg/kg body weight). In the acute hypolipidemic study, mice treated with the HWCE and its fractions exhibited a significant (P < 0.001) reduction in plasma total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) levels. Importantly, immature carob aqueous extract was more effective in lowering mice hypercholesterolemia than its fractions. Indeed, mice fed the HFCD for 12 weeks showed a significant raise in plasma TC, TG and LDL-C, as well as in hepatic and fecal TC and TG levels. The HWCE at 100 and 200 mg/kg body weight significantly (P < 0.001) reversed the plasmatic levels of these lipid parameters, increased plasma HDL-C level, reduced hepatic lipids accumulation, but increased cholesterol level in the bile and fecal lipids excretion. The HWCE decreased also the atherogenic index, the LDL-C/HDL-C ratio and plasma glucose level after 12 weeks’ experiment. On the other hand, the HWCE was more effective in preventing mice lipoprotein-rich plasma oxidation than its fractions, with a concentration-dependent manner. Conclusion: C. siliqua green fruits extract could be effective in preventing atherosclerosis and related cardiovascular complications through the inhibition of lipoprotein oxidation and cholesterol clearance.

Phytosterol of lotus seed core powder alleviates hypercholesterolemia by regulating gut microbiota in high-cholesterol diet-induced C57BL/6J mice

The present study aimed to investigate the regulatory mechanisms of lotus seed core powder phytosterol extract (LSP-PE) on hypercholesterolemia and intestinal microbiota in high-cholesterol diet (HCD)-induced C57BL/6 J mice. Gavage with LSP-PE reduced levels of serum total cholesterol (TC), ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C), hepatic TC, hepatic triglyceride (TG), hepatic LDL-C, hepatic very low-density lipoprotein (VLDL), fecal TC and fecal total bile acid (TBA), while augmented hepatic HDL-C content. In contrast with HCD group, high-dose LSP triggered significant diminutions of serum ALT, serum AST, hepatic ALT and hepatic AST levels in HCD-fed mice, which were 16.49, 28.94, 43.42, and 44.47%, respectively, thus remarkably ameliorating the pathological changes of liver and small intestine. In-depth genetic research found that LSP was effective in down-regulating the expression of cholesterol metabolism related genes including Niemannpick C1-like protein 1 (NPC1L1), acyl-coA cholesterol acyl-transferase 2 (ACAT2), microsomal triglyceride transporter (MTP) and ATP binding cassette subfamily G member 5 (ABCG5). Moreover, LSP-PE could restore the disorder of intestinal flora via augmenting the Actinobacteria abundance as well as decreasing the Firmicutes/Bacteroidetes ratio and abundances of Proteobacteria and Verrucomicrobia to regulate cholesterol metabolism-related genes. In summary, LSP-PE possessed excellent cholesterol-lowering activity by positively regulating the gut microbiota and the expression levels of genes related to cholesterol absorption and metabolism. Therefore, this work suggested LSP phytosterol as a potential supplement to alleviate the symptoms of hypercholesterolemia.

Effects of fruits and vegetables on gut microbiota in a mouse model of metabolic syndrome induced by high-fat diet.

The aim of this study was to evaluate the effect of fruit and vegetable intake on gut microbiota using a mouse model of metabolic syndrome (MS) induced by a high-fat diet. Forty-eight male mice were randomly divided into four groups, control group (C), high-fat diet-fed model group (H), high fat plus low intake of fruits and vegetables diet-fed group (H.LFV), high fat plus high intake of fruits and vegetables diet-fed group (H.HFV), and each group were fed for 60 days. During the experiment, mouse body weights were recorded and fecal samples were collected. Cetyltrimethyl ammonium bromide (CTAB) method was used to extract fecal bacterial DNA, and the purity and concentration of the DNA were detected by electrophoresis. DNA samples underwent PCR amplification (primers in 16 S V4 (515F and 806R)). Raw sequencing data were processed, and sample complexity and multiple-sample comparisons were investigated. Mouse organ coefficient, serum lipid levels, fecal TC (total cholesterol) and TBA (total bile acid) levels, and hepatic glutathione and malondialdehyde levels were determined. Compared to the H group, the fecal TC and TBA levels decreased significantly in the H.HFV group (p < .05), and hepatic glutathione and malondialdehyde levels decreased significantly in both H.LFV and H.HFV groups (p < .05). Decreased abundance of Firmicutes, Burkholderiales, Syntrophomonas, and Pseudomonadales in gut microbiota was observed in H.LFV and H.HFV groups compared to the H group. The Anosim results showed significant differences in pairwise comparison between groups. The linear discriminant analysis effect size (LEfSe) results showed that k_bacteria not only exhibited statistically differences between H and C groups but also among H.LFV, H.LFV, and H groups, and hence, could be used as a biomarker between groups. To sum up, fruit and vegetable powder could increase the fecal excretion of TC and TBA, and the antioxidant capacity in C57BL/6N mice. Meanwhile, the mechanism that fruit and vegetable powder could prevent MS in C57BL/6N mice was related to the decreased abundance of gut microbiota, including Firmicutes, Syntrophomonadales, and Pseudomonadales. Hence, fruit and vegetable powder could be used as a recommended food to regulate gut microbiota and prevent the occurrence of MS-related diseases.

Effects of resistant starch III on the serum lipid levels and gut microbiota of Kunming mice under high-fat diet

Resistant starch III (RS3), as a prebiotic, provides health benefits. This study aimed to investigate the role of RS3 in lowering serum lipids and regulating gut microbiota by administering Novelose 330 to Kunming (KM) mice. The results demonstrated that RS3 intervention significantly decreased body weight, food intake, levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and liver fat. RS3 could remarkably improve the quality of the entire cecum, quality of the cecal wall, and wall surface area of mice; enhance the moisture content; and reduce the pH value. Moreover, the decrease in the liver TC content and the increase in the fecal TC content were related to RS3 intervention. The concentrations of total short-chain fatty acids (SCFAs) in the colon and individual levels of acetate, propionate, and butyrate increased with RS3 supplementation. An Illumina-based sequencing approach showed that RS3 notably increased the Bacteroides/Firmicutes ratio in the mice fed a high-fat diet. At the genus level, the relative abundance of Bacteroides, Ruminococcus, and Bifidobacterium and the number of main SCFA producers increased in the mice fed an RS3 diet. These findings provided insights into specific gut microbiota shifts to the hypolipidemic effect of RS3.

Anti‐obesity effect of Premature Citrus Extract in high‐fat diet induced obesity mice

BackgroundObesity is a worldwide health threat. Premature citrus extract (PCE) are known to contain high concentrations of flavonoids, polyphenols, and organic acids with health functions. The current study aimed to investigate the anti‐obesity effect of PCE on a high‐fat diet (HFD)‐induced obesity mice.MethodMice were fed on chow or HFD with or without Orlistat (ORL), Hesperidin (HES), and PCE treatment for 10 weeks. Triglyceride (TG) content and total cholesterol (TC), and low‐density lipoprotein cholesterol (LDL‐c), and high‐density lipoprotein cholesterol (HDL‐c) levels were determined by TG, HDL and LDL Assay Kit (BioAssay System). The phosphorylation levels of AMP‐activated protein kinase (AMPK) and acetyl Co‐A carboxylase (ACC); the expression of sterol regulatory element binding protein‐2 (SREBP‐2), 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGCR), Acyl‐coenzyme A: cholesterol acyltransferases (ACAT‐1) and mitochondrial uncoupling proteins (UCP‐3) were observed via western blot analysis.ResultsPCE and HES administered group significantly reduced the weights of body, liver, and white adipose tissue compared to the HFD group. Supplementation with PCE and HES significantly decreased the levels of TG, TC, and (LDL‐c), and increased (HDL‐c) levels in serum compared to the HFD group. Furthermore, treatment with PCE and HES significantly decreased the levels of TG and TC in the liver whereas increased the levels of TG and TC in feces compared to the HFD group. Western blot analysis revealed that PCE and HES increased the phosphorylation levels of both AMPK and ACC and significantly decreased the expression levels of SREBP‐2, HMGCR, and ACAT‐1 in the liver compared to the HFD group. In addition, both PCE and HES increased the expression level of UCP‐3 in skeletal muscle tissue.ConclusionOverall results suggest that PCE and HES exerts an anti‐obesity effect via activation of AMPK and associated signaling cascades related to lipid metabolism in HFD‐induced obesity mice

Prevention of High-Fat Diet-Induced Hypercholesterolemia by Lactobacillus reuteri Fn041 Through Promoting Cholesterol and Bile Salt Excretion and Intestinal Mucosal Barrier Functions

Objectives:Lactobacillus reuteri Fn041 (Fn041) is a probiotic isolated from immunoglobulin A coated microbiota in the human breast milk of Gannan in China with a low incidence of hypercholesterolemia. This study aims to explore the role and mechanism of Fn041 in preventing hypercholesterolemia caused by a high-fat diet in mice.MethodsC57BL/6N mice were fed a low-fat diet or a high-fat diet and gavage with Fn041 and Lactobacillus rhamnosus GG (LGG) for 8 weeks.ResultsBoth Fn041 and LGG prevented the occurrence of hypercholesterolemia, liver and testicular fat accumulation. In addition, a high-fat diet causes intestinal dysbiosis and mucosal barrier damage, which is associated with hypercholesterolemia. Fn041 prevented the high-fat diet-induced reduction in alpha diversity of intestinal microbiota and intestinal mucosal barrier damage. Fn041 treatment significantly increased fecal total cholesterol and total bile acids.ConclusionsFn041 prevented hypercholesterolemia by enhancing cholesterol excretion and mucosal barrier function.

Evaluation of the Cholesterol-Lowering Mechanism of Enterococcus faecium Strain 132 and Lactobacillus paracasei Strain 201 in Hypercholesterolemia Rats.

Hypercholesterolemia can cause many diseases, but it can effectively regulated by Lactobacillus. This study aimed to evaluate the cholesterol-lowering mechanism of Enterococcus faecium strain 132 and Lactobacillus paracasei strain 201. These results showed that both the strains decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), liver TC and TG and increased fecal TC, TG and total bile acid (TBA) levels. Additionally, both strains also reduced glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and levels of tissue inflammation levels to improve the lipid profile, and they reduced fat accumulation partially by alleviating inflammatory responses. Furthermore, both strains regulated the expression of the CYP8B1, CYP7A1, SREBP-1, SCD1 and LDL-R gene to promote cholesterol metabolism and reduce TG accumulation. Interventions with both strains also altered the gut microbiota, and decreasing the abundance of Veillonellaceae, Erysipelotrichaceae and Prevotella. Furthermore, fecal acetic acid and propionic acid were increased by this intervention. Overall, the results suggested that E. faecium strain 132 and L. paracasei strain 201 can alleviate hypercholesterolemia in rats and might be applied as a new type of hypercholesterolemia agent in functional foods.

Study on anti-hyperlipidemia effect of Linderae Radix via regulating reverse cholesterol transport

This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.

Evaluation of Beneficial and Adverse Effects of a Diet Supplemented with Schisandrae Fructus Seed Ethanol Extract on Lipid and Glucose Metabolism in Normal and Hypercholesterolemic/Hyperglycemic Mice.

Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baillon, has been used for the treatment of liver injury and metabolism-related disorders in China. The objective of this study was to investigate the effects of supplementation with ethanol extract of SF seed (EtSF-S) on serum/hepatic lipid and glucose levels as well as fecal total cholesterol (TC) contents in mice fed a normal diet (ND) or high-fat/fructose diet (HFFD) containing 15% lard oil and 15% fructose. Female ICR mice (18–20 g in body weight) were fed with ND or HFFD for 3 months, and then EtSF-S was added to both chow diets at increasing concentrations of 1, 5, and 10% (w/w). Thirty days later, serum and hepatic lipids, including TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose, were measured. Dietary supplementation with EtSF-S reduced hepatic TC (36 and 18%) and TG levels (38 and 28%) and increased serum HDL/LDL ratio (16 and 26%) in both ND- and HFFD-fed mice, respectively. Moreover, supplementation with EtSF-S elevated serum HDL (31%) in HFFD-fed mice and reduced serum LDL (27%) in ND-fed mice. EtSF-S treatment reduced fat mass (40%) in ND-fed mice and increased fecal TC contents (33%) in HFFD-fed mice. EtSF-S supplementation decreased hepatic glucose contents (29%) in both ND- and HFFD-fed mice. However, diet supplemented with EtSF-S elevated serum TG levels (up to 123%) and hepatic size (28%), but more importantly, suppressed the body weight gain (approximately 130%) in mice fed with HFFD. These findings suggested that dietary supplementation with EtSF-S as natural herbal function food may be a useful strategy for the treatment of patients with fatty liver disease or overweight without a high intake of sugar and fat.

Beneficial Effects of Algerian Green Alga Ulva lactuca and Its Hydroethanolic Extract on Insulin Resistance and Cholesterol Reverse Transport in High-Fat/Streptozotocin Diabetic Rats

The aim of this study was to evaluate the impact of the green algae Ulva lactuca and its hydroethanolic extract on insulin resistance and cholesterol reverse transport in type 2 diabetic (T2D) rats. Rats had T2D induced by a high-fat diet (HFD) for 5 weeks followed by intraperitoneal injection of streptozotocin. Diabetic rats were divided into three groups and were fed a HFD in the presence or absence of 1% alga (HFD-Alg) or 1% of its hydroethanolic extract (HFD-Ext), for 4 weeks. The control group consumed 20% casein combined with 5% lipids. Hyperglycemia, insulin resistance, hypercholesterolemia, and hypertriglyceridemia were noted in HFD rats vs control rats. Whole alga and its extract decreased these parameters vs the HFD. Moreover, fecal total cholesterol and triacylglycerols levels were lowered in HFD group vs C group, but were increased with HFD-Alg vs HFD. Compared with the Control, the HFD group had decreased lecithin:cholesterol acyltransferase (LCAT) activity, apolipoprotein A-I (ApoA-I), high-density lipoprotein (HDL3)-phospholipids (PL), and HDL2-cholesteryl ester (CE) levels, but increased HDL3-unesterified cholesterol (UC) levels. Furthermore, compared with the HFD group, the HFD-Alg and HFD-Ext groups had increased LCAT activity, ApoA-I, HDL3-PL, and HDL2-CE levels and decreased HDL3-UC levels. In addition, in the HFD-Ext group, LCAT activity and ApoA-1 levels were decreased vs the HFD-Alg whereas HDL3-UC levels were increased. In conclusion, these results indicate that U. lactuca and its hydroethanolic extract have curative effect on T2D. Therefore, this alga could be considered a functional food supplement for the treatment and prevention of diabetes.

Lactobacillus delbrueckii Interfere With Bile Acid Enterohepatic Circulation to Regulate Cholesterol Metabolism of Growing-Finishing Pigs via Its Bile Salt Hydrolase Activity.

Microbiota-targeted therapies for hypercholesterolemia get more and more attention and are recognized as an effective strategy for preventing and treating cardiovascular disease. The experiment was conducted to investigate the cholesterol-lowering mechanism of Lactobacillus delbrueckii in a pig model. Twelve barrows (38.70 ± 5.33 kg) were randomly allocated to two groups and fed corn–soybean meal diets with either 0% (Con) or 0.1% Lactobacillus delbrueckii (Con + LD) for 28 days. L. delbrueckii–fed pigs had lower serum contents of total cholesterol (TC), total bile acids (TBAs), and triglyceride, but higher fecal TC and TBA excretion. L. delbrueckii treatment increased ileal Lactobacillus abundance and bile acid (BA) deconjugation and affected serum and hepatic BA composition. Dietary L. delbrueckii downregulated the gene expression of ileal apical sodium-dependent bile acid transporter (ASBT) and ileal bile acid binding protein (IBABP), and hepatic farnesoid X receptor (FXR), fibroblast growth factor (FGF19), and small heterodimer partner (SHP), but upregulated hepatic high-density lipoprotein receptor (HDLR), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2), and cholesterol-7α hydroxylase (CYP7A1) expression. Our results provided in vivo evidence that L. delbrueckii promote ileal BA deconjugation with subsequent fecal TC and TBA extraction by modifying ileal microbiota composition and induce hepatic BA neosynthesis via regulating gut–liver FXR–FGF19 axis.

Comparison of main chemical composition of Plantago asiatica L. and P. depressa Willd. seed extracts and their anti-obesity effects in high-fat diet-induced obese mice

BackgroundNowadays, the pharmacological effects of Plantaginis semen was getting more and more attention because of the great effect of treating diuresis, hypertension, hyperlipidemia, and hyperglycemia. According to the Chinese Pharmacopoeia, Plantaginis semen is the seed of Plantago asiatica L. or P. depressa Willd. This was verified by examining chemical composition differences in a preliminary experiment, predicting their differences in pharmacology. PurposeIn this study, we aimed to compared the the differences in main components and anti-obesity effects of Plantago asiatica L. seed extract (PASE) and P. depressa Willd. seed extract (PDSE). Study design and methodsThe ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) analysis was used to characterize and compare the differences chemical constituents of PASE and PDSE. The difference therapeutic effects between PASE and PDSE on obesity and associated metabolic disorders was investigated by high-fat (HF) diet induced mice model. ResultsThe fingerprint of Plantaginis semen were established by screening and identified 15 main components, including iridoids, phenethanol glycosides, flavonoids, guanidines, and fatty acids. Pentahydroxy flavanone was observed only in PDSE but not in PASE. The quantitative analysis results indicated that the main bioactive components in PASE were geniposidic acid and acteoside; their concentrations were three times higher in PASE than in PDSE. In anti-obesity effects, the result show the levels of fasting blood glucose were improved in both PASE and PDSE when compared with the HF group, while the PASE is show a significant effect then the PDSE group and improved the glucose tolerance but not in PDSE. The results also displayed that the Plantaginis semen did not modify food intake or body weight but decreased abdominal white/brown adipocyte size, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), hepatic TG and TC, fecal TG and TC concentrations when compared with the HF group. Among these indicators, serum TG, liver TG, fecal TC and TG levels were significantly improved in PASE compared with PDSE. The results indicated that PASE treatment more effectively improved lipid and glucose metabolism in HF diet-induced obese mice than did PDSE. ConclusionAs Plantaginis semen sources, P. asiatica L. seeds demonstrated more bioactive components and favorable metabolic disorder treatment outcomes than did P. depressa Willd. seeds.

Palmatine regulates bile acid cycle metabolism and maintains intestinal flora balance to maintain stable intestinal barrier

ObjectivePalmatine (PAL) is a natural isoquinoline alkaloid that has been widely used in the pharmaceutical field. The current study aimed to investigate the function of PAL in improving hyperlipidemia induced by high-fat diet (HFD) in rats. MethodsBiochemical analysis of triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDLC) was performed on rats. Total bile acid (TBA) and stool TC and TBA were also measured to assess the changes in total bile acid excretion. RT-qPCR was employed to detect the expression of genes related to bile acid metabolism, and the Western blot assay was used to detect the levels of CYP7A1, ZO-1, ZO-2, and Claudin-1. The siRNA experiment was employed to further investigate whether PAL regulated CYP7A1 through PPARα. Lipopolysaccharide (LPS) and FITC-dextran (FD-4) were also tested to assess the intestinal permeability. ResultsAL-treated rats had lower TC, TG, LDL-C levels, lower serum TBA levels, and increased fecal TBA and TC levels. Furthermore, CYP7A1 protein expression was up-regulated in PAL-treated rats. Additionally, PAL regulated bile acid metabolism by up-regulating the expression of CYP7A1 and PPARα and down-regulating the expression of FXR. Besides, the area of plasma FD-4 and LPS content in the PAL group were reduced, and the expression of proteins ZO-1, ZO-2 and Claudin-1 related to intestinal permeability was increased. ConclusionAll in all, PAL could mediate the PPARα-CYP7A1 pathway to maintain the balance of intestinal flora, regulate the bile acid metabolism, and reduce the blood lipids of rats, thereby protecting against hyperlipidemia.

Comparative Effects and Mechanisms of Chitosan and Its Derivatives on Hypercholesterolemia in High-Fat Diet-Fed Rats.

The present study investigated and compared the effects of different molecular weights of chitosan (high molecular weight chitosan (HC) and low molecular weight chitosan (LC)) and its derivatives (chitosan oligosaccharide (CO)) on cholesterol regulation in high-fat (HF) diet-fed rats. A diet supplementation of 5% HC, 5% LC, or 5% CO for 8 weeks showed hypocholesterolemic potential in HF diet-fed rats. Unexpectedly, a 5% CO-supplemented diet exerted hepatic damage, producing increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-α). The supplementation of HC and LC, unlike CO, significantly decreased the hepatic total cholesterol (TC) levels and increased the fecal TC levels in HF diet-fed rats. The hepatic protein expression of the peroxisome proliferator-activated receptor-α (PPARα) in the HF diet-fed rats was markedly decreased, which could be significantly reversed by both HC and LC, but not CO, supplementation. Unlike the supplementation of CO, both HC and LC supplementation could effectively reverse the HF-inhibited/induced gene expressions of the low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1), respectively. The upregulated intestinal acyl-CoA cholesterol acyltransferase 2 (ACAT2) protein expression in HF diet-fed rats could be reversed by HC and LC, but not CO, supplementation. Taken together, a supplementation of 5% CO in HF diet-fed rats may exert liver damage via a higher hepatic cholesterol accumulation and a higher intestinal cholesterol uptake. Both HC and LC effectively ameliorated the hypercholesterolemia and regulated cholesterol homeostasis via the activation and inhibition of hepatic (AMPKα and PPARα) and intestinal (ACAT2) cholesterol-modulators, respectively, as well as the modulation of downstream signals (LDLR and CYP7A1).

Cholesterol Lowering and Antioxidative Effect of Pregerminated Brown Rice in Hypercholesterolemic Rats.

Pregerminated brown rice (GBR) is assumed to be more beneficial than polished white rice (WR), with regard to nutrition and cardiovascular health. To support this with scientific evidence, cholesterol-lowering and antioxidative effects of GBR were studied in the present investigation. The most popular rice variety in Bangladesh BIRI-29 was used to prepare GBR and WR. Initially, we analyzed the proximate composition, antioxidative phytochemicals, in vitro 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging ability and anti-hemolytic effects of GBR. To examine the dietary impact and possible benefits of the GBR, experimentally-induced hypercholesterolemic (HC, 1% cholesterol) rats were fed with GBR against WR for 12 wk. At the end, plasma total cholesterol (TC), low- and high-density lipoprotein-cholesterol (LDL-C and HDL-C), triglyceride (TG), fecal TC, and hepatic TC, lipid peroxide (LPO) and proinflammatory TNFα levels were determined. Relative to WR, GBR contained higher amounts of total polyphenols, total flavonoids, β-carotene and lycopene, and exhibited a stronger in vitro DPPH-free radical scavenging ability and antihemolytic potentials. Levels of plasma TC, LDL-C, TG, and hepatic TC and TG significantly decreased, while plasma HDL-C and fecal TC levels significantly increased in the GBR-fed HC-rats, indicating dietary GBR demonstrates a stronger antilipidemic effect than WR. The hepatic levels of LPO and TNFα also decreased (p<0.05) to a greater extent in GBR-fed HC-rats than those in the WR-fed rats. It is thus concluded that dietary GBR could be a natural treatment of hypercholesterolemia and related cardiovascular risk factors, and a source of antioxidants to reduce hemolysis and related anemia.

Effect of bile salt hydrolase-active Lactobacillus plantarum KLDS 1.0344 on cholesterol metabolism in rats fed a high-cholesterol diet

• L. plantarum KLDS 1.0344 was assayed for BSH activity and hypocholesterolemic effect. • L. plantarum KLDS 1.0344 improved lipid profiles and metabolic pathway in rats. • L. plantarum KLDS 1.0344 regulated hepatic CYP7A1 and HMGCR expression in rats. • L. plantarum KLDS 1.0344 modulated intestinal NPC1L1, ABCG5/8 and ABCA1 expression. The present study aimed to evaluate bile salt hydrolase (BSH) activity and hypocholesterolemic effect of Lactobacillus plantarum KLDS 1.0344. BSH activity of the strain KLDS 1.0344 varied with different bile salts. High-cholesterol diet-induced male Sprague-Dawley rats were simultaneously administrated with strain KLDS 1.0344 for 4 weeks. The strain KLDS 1.0344 significantly improved lipid profiles in serum and liver, and increased fecal total cholesterol and total bile acids levels in high-cholesterol diet-fed rats ( P < 0.05), and superior to L. rhamnosus GG. Moreover, expressions of genes related to cholesterol metabolism were regulated by the strain KLDS 1.0344, including down-regulation of hepatic HMGCR and FXR and intestinal NPC1L1, and up-regulation of intestinal LXRα, ABCG5, ABCG8 and ABCA1 and hepatic CYP7A1 ( P < 0.05). The hypocholeseterolemic effect of L. plantarum KLDS 1.0344 was modulated most likely by pathway of cholesterol absorption, synthesis, and catabolism, which might be partly due to its BSH activity.

Evaluation of hypolipidemic peptide (Val-Phe-Val-Arg-Asn) virtual screened from chickpea peptides by pharmacophore model in high-fat diet-induced obese rat

Chickpea peptides (ChPs) were found to significantly decrease serum total cholesterol (TC), total triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) content, and increase serum high-density lipoprotein cholesterol (HDL-C) content (P < 0.05) in high fat diet-induced obese rats. The activities of fatty acid synthetase (FAS) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) could be significantly inhibited by ChPs. Additionally, peroxisome proliferator-activated receptors (PPAR)α and LDL receptor (LDLR) expressions were up-regulated, and sterol regulatory element-binding protein (SREBP)-2 expression was down-regulated by ChPs significantly (P < 0.05). Fecal TC and bile acid (TBA) were also found to be increased significantly (P < 0.05) in ChPs with high-fat diet treatment groups. Moreover, the micellar solubility of cholesterol decreased after the treatment with ChPs in vitro. A reductase (HMGR) inhibitor (VFVRN) was found using pharmacophore model. VFVRN was found to have high hypolipidemic effects by using Hypo1, which was a novel scaffold of HMGR. VFVRN was confirmed in HepG2 cell that it could inhibit the TC synthesis by decreasing the expressions of SREBP-1c, SREBP-2, liver X receptor (LXR)α and HMGR.