Search Results (14)

Background: Stigmasterol (St) holds promise as a natural cholesterol-lowering agent, yet its poor aqueous solubility and low bioaccessibility severely constrain its application in functional foods. Methods: In this study, we exploited whey protein peptides (WPP) with intrinsic cholesterol esterase (CEase) inhibitory activity to construct St-loaded self-assembled nanoparticles. Subsequently, we investigated its physicochemical properties and formation mechanism and evaluated its hypocholesterolemic activity through animal experiments. Results: Driven by non-covalent hydrophobic and hydrogen-bonding interactions, the optimized St-loaded WPP nanoparticles (St@WPP) ((234.47 ± 1.36) nm) achieved a high encapsulation efficiency (EE) of 74.73% ± 2.19%. This nano-encapsulation markedly improved St dispersibility and storage stability, and significantly elevated its bioaccessibility from 9.00% ± 0.14% to 19.41% ± 0.69% after simulated gastrointestinal digestion. St@WPP administration effectively ameliorated dyslipidemia, as evidenced by reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), which may be associated with reduced intestinal cholesterol availability and increased fecal cholesterol content. Moreover, St@WPP alleviated hepatic steatosis, attenuated systemic inflammation, and rebalanced gut microbiota architecture. Conclusions: Collectively, the WPP shell functions as a delivery carrier that improves the water solubility and bioaccessibility of St, thereby broadening its potential for application in low-fat or aqueous-based food systems. The resulting St@WPP exhibits notable cholesterol-lowering activity, positioning it as a promising functional food ingredient with potential benefits for cholesterol management. Full article

Obesity and its metabolic complications represent a major global health challenge, and food-derived bioactive peptides are emerging as promising dietary interventions. In this study, two hemp seed protein-derived tetrapeptides with pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory activity, APAM and RLPA, were co-administered with a high-fat diet (HFD) to male C57BL/6J mice at 25 and 100 mg/kg body weight for 10 weeks. Both peptides dose-dependently alleviated HFD-induced body weight gain, visceral fat accumulation, hepatic steatosis, dyslipidemia, hyperglycemia, and systemic inflammation. Mechanistically, both peptides inhibited intestinal PL and CE activities and enhanced fecal lipid excretion, supporting direct suppression of intestinal fat digestion. 16S rRNA gene sequencing revealed partial restoration of HFD-disrupted gut microbiota, with APAM preferentially enriching Bifidobacterium and Roseburia, while RLPA promoted Akkermansia and Lactobacillus, accompanied by differential improvements in fecal short-chain fatty acid (SCFA) profiles. Hepatic transcriptomics identified the PPAR signaling pathway as a shared regulatory hub, and multi-omics integration revealed significant correlations linking gut microbiota, SCFA production, hepatic gene expression, and metabolic phenotypes. These findings suggest a dual-pathway anti-obesity mechanism integrating intestinal lipid digestion inhibition with gut–liver axis modulation, and highlight hemp seed protein-derived peptides as potential functional food ingredients for obesity prevention. Full article

Guava (Psidium guajava L.) processing produces peels, seeds, and residual pulp. Previous studies have shown that this fraction contains a significant amount of bioactive molecules (more than in the pulp), such as phenolic compounds, which have demonstrated health-beneficial bioactivities, including antioxidant, anti-obesogenic, and antihyperlipidemic activities, among others. In this study, we aimed to characterize total phenolic compounds, total flavonoids, the phenolic profile, and the in vitro antioxidant and antihyperlipidemic properties of guava byproduct extracts, which were evaluated for their potential use as functional ingredients. Phenolic analysis indicated the total phenolic content (46.45 mg GAE/g), the total flavonoid content (3.86 mg CE/g), and contents of individual phenolic compounds, namely ellagic, syringic, rutin, luteolin, and kaempferol. The extracts showed good antioxidant activity (236.22, 344.89, and 387.1 µmol TE/100 g for TEAC, DPPH, and FRAP, respectively). Moreover, the extracts could bind bile acids (18.50–40.34%) and reduce cholesterol solubility in artificial micelles (53.0–67.6%). Modest pancreatic lipase inhibition (33.33%), stronger cholesterol esterase inhibitory activities (60.22%), and mild HMG-CoA inhibitory potential (16.90%) were recorded. Guava processing byproducts demonstrate the potential to be considered as value-added ingredients in functional foods. Full article

Stingless bee honey (SBH) contains bioactive compounds which are influenced by its botanical origin, and these constituents are closely associated with its health-promoting properties. Interest in monofloral honey has been increasing owing to its distinctive sensory characteristics, relatively consistent nutritional composition, and higher market value. The growing burden of cardiometabolic disease underscores the need for additional studies examining the inhibition of enzymes relevant to these pathways. This study analyzed SBH from five botanical origins (acacia, coconut, elderberry, Singapore rhododendron, sunflecks). In vitro inhibition was evaluated against enzymes associated with cholesterol biosynthesis (HMG-CoA reductase), blood pressure regulation (ACE), lipid digestion (pancreatic lipase, cholesterol esterase), and postprandial glycaemia (α-amylase, α-glucosidase). Acacia SBH showed the most potent ACE inhibition (16.80 ± 0.30 mg/mL), while Singapore rhododendron SBH exhibited the strongest HMG-CoA reductase inhibition (18.05 ± 0.50 mg/mL). Sunflecks SBH showed the most potent inhibition of cholesterol esterase, with the lowest IC₅₀ (57.00 ± 0.01 mg/mL). The findings suggest the potential of SBH as a cardioprotective functional food with significant health benefits. Full article

To address the limited functional diversity of traditional kombucha, this study utilized red yeast rice (RYR) as an alternative substrate and prepared three samples: black tea kombucha (KBT), black tea-red yeast rice mixed kombucha (KBL, at a 1:1 ratio), and red yeast rice kombucha (KRY). After 9 days of fermentation, KRY exhibited the lowest pH, the highest total acidity, and notable sugar metabolic activity. It exhibited in vitro inhibition rates of 82.8%, 78.2%, 70.3%, and 76.9% against cholesterol esterase, pancreatic lipase, α-glucosidase, and α-amylase, respectively, indicating potential hypoglycemic and hypolipidemic activities. In contrast, KBT maintained the strongest antioxidant capacity, with scavenging rates exceeding 90% against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS). A total of 72 volatile flavor compounds (VFCs) were identified, with 7 key compounds enriched in KRY, which enhanced its sensory acceptance and received the highest scores in color, clarity, and aroma. Microbial community analysis revealed the post-fermentation dominance of Komagataeibacter, Acetobacter, and Saccharomyces, which correlated positively with key VFCs. These findings indicate that RYR as a substrate enhances functional microbial growth, sugar metabolism, organic acid production, flavor enrichment, and in vitro inhibitory activity of enzymes associated with hypoglycemic and hypolipidemic effects. Full article

Hyperlipidemia, marked by high levels of fats in the blood, is a major risk factor for non-communicable diseases such as type 2 diabetes, cardiovascular diseases, and cancer. It has been linked to the action of reactive oxygen species and the formation of advanced glycation end products. Current treatments for hyperlipidemia, like orlistat, simvastatin, and atorvastatin, often present undesirable side effects, prompting the need for new therapeutic agents that are safer, more effective, cost-efficient, and have fewer side effects. In this context, new compounds, specifically propano- and butanosulfonic acids with 9-substituted quinobenzothiazinyl substituents, were synthesized through reactions with 9-substituted quinobenzothiazines and propane sultone or butane sultone. These novel quinobenzothiazine derivatives were verified using ¹H NMR, ¹³C NMR, and HR-MS techniques. The research focused on assessing these compounds for their toxicity, ability to prevent glycation, antioxidant properties, and their potential to combat hyperlipidemia. Toxicity was evaluated on the 3T3 L1 fibroblast cell line using the MTT assay. The capacity to prevent glycation was tested with bovine serum albumin–methylglyoxal and bovine serum albumin–glucose systems. This study measured total reactive oxygen species in the 3T3 L1 cell line using 2′,7′-dichlorodihydrofluorescein diacetate staining, and antioxidant capacity was assessed through DPPH scavenging and metal ion chelation tests. The effectiveness against hyperlipidemia was determined by targeting cholesterol esterase and pancreatic lipase activities, with concentrations of the compounds 5 to 12 ranging from 0.0245 to 0.268 μM. Standard drugs such as orlistat, simvastatin, statins, and aminoguanidine were used as positive controls in various assays. Additionally, computational docking studies with AutoDock Vina were performed. The resulting findings indicated that the compounds were non-toxic to cells, effectively inhibited key enzymes related to hyperlipidemia, and showed significant antioxidant properties, including the prevention of advanced glycation end-product formation. Compounds 11 and 12 demonstrated the highest activity levels. These promising results highlight the potential of new quinobenzothiazine derivatives as lead compounds for the development of antihyperlipidemic drugs, although further research is necessary to confirm their efficacy and safety. Full article

Despite the many current cholesterol-lowering drugs on the market, the persistent surge of hypercholesterolemic-related complications ignites a fascinating search for the discovery of novel therapeutics. This study aimed at investigating the anti-hypercholesterolemic effect of Bauhinia bowkeri extracts. The plant material was sequentially extracted with n-hexane, dichloromethane (DCM), and 70% ethanol. The phytochemical constituents of the extracts were analyzed through GC-MS and the antioxidant activity of the extracts was screened against a wide range of free radicals (ABTS, DPPH, hydroxyl radical, and nitric oxide). The extracts were also screened for the metal iron chelating and reducing power potential. The enzyme inhibitory activity of the extracts on pancreatic lipase, cholesterol esterase, and HMG-CoA reductase as well as the bile acid binding capacity were evaluated. Among the total of 122 compounds detected in the three extracts, only 7 compounds (E-15-Heptadecenal, Diethyl Phthalate, 9,12,15-Octadecatrienoic acid ethyl ester, (Z,Z) Tetradecane 5-methyl, and Octadecane 5-methyl) were found to be common in all the extracts. The extract displayed a varying degree of efficiency on free radicals with IC₅₀ values ranging from 0.07 mg/mL to 0.41 mg/mL. A concentration-dependent inhibition of pancreatic lipase and cholesterol esterase activities, along with a reduction in the bile-binding capacity exhibited by the extracts, was noted. In silico investigations of some of the phytoconstituent revealed significant inhibition of HMG-CoA reductase, cyclooxygenase, and hormone-sensitive lipase with a binding affinity that ranged between −5.1 and −7.0 kcal/mol. These findings suggest that Bauhinia bowkeri extracts possess potential antioxidant and anti-hypercholesterolemic properties. Full article

In this work, the hypolipidemic and antioxidative capacity of FSGLR (S7) and GIEWA (S10) from miiuy croaker swim bladders was explored systematically in an oleic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model of HepG2 cells. Moreover, the hypolipidemic activity of S7 and S10 and their antioxidative abilities were preliminarily investigated in combination with molecular docking technology. The results indicated that S7 and S10 could decrease the amount of lipid accumulation and the content of triglycerides (TG) and total cholesterol (TC) in the OA-induced NAFLD cell model in a dose-dependent manner. In addition, S7 and S10 exhibited better bile salt binding, pancreatic lipase (PL) inhibition, and cholesterol esterase (CE) inhibition capacities. The hypolipidemic mechanisms of S7 and S10 were connected with the downregulation of the mRNA expression levels of adipogenic factors, including sterol-regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), sterol-regulatory element-binding protein (SREBP)-2, hydroxymethylglutaryl-CoA reductase (HMGR), and fatty acid synthase (FAS) (p < 0.01), and the upregulation of the mRNA expression of β-oxidation-related factors, including carnitine palmitoyltransferase 1 (CPT-1), acyl-CoA oxidase 1 (ACOX-1), and peroxisome proliferator-activated receptor α (PPARα). Moreover, FSGLR (S7) and GIEWA (S10) could significantly protect HepG2 cells against OA-induced oxidative damage, and their antioxidant mechanisms were related to the increased activity of intracellular antioxidant proteases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; catalase, CAT) to remove excess reactive oxygen species (ROS) and decrease the production of malondialdehyde (MDA). The presented findings indicate that the hypolipidemic and antioxidant functions and mechanisms of S7 and S10 could make them potential hypolipidemic and antioxidant candidates for the treatment of NAFLD. Full article

The bioactive peptides derived from yak milk cheese exhibited cholesterol-lowering properties. However, there was limited research on their inhibitory effects on cholesterol esterase (CE) and elucidation of their potential inhibitory mechanisms. In this study, we identified CE-inhibiting peptides through virtual screening and in vitro assays. Additionally, molecular docking and molecular dynamics studies were conducted to explore the mechanisms. The results indicated that peptides RK7 (RPKHPIK), KQ7 (KVLPVPQ), QP13 (QEPVLGPVRGPFP), TL9 (TPVVVPPFL), VN10 (VYPFPGPIPN), LQ10 (LPPTVMFPPQ), and SN12 (SLVYPFPGPIPN) possessed molecular weights of less than 1.5 kDa and a high proportion of hydrophobic amino acids, demonstrating notable inhibitory effects on CE. Molecular docking and dynamics revealed that peptides RK7, KQ7, QP13, and VN10 bound to key amino acid residues Arg423, His435, and Ser422 of CE through hydrogen bonds, hydrophobic interactions, salt bridges, and π–π stacking, occupying the substrate-binding site and exerting inhibitory effects on CE. The four peptides were further synthesized to verify their CE-inhibitory effects in vitro. RK7, KQ7, QP13, and VN10 exhibited inhibitory activity on CE with IC₅₀ values of 8.16 × 10⁻⁷ mol/L, 8.10 × 10⁻⁷ mol/L, 4.63 × 10⁻⁷ mol/L, and 7.97 × 10⁻⁷ mol/L; RK7, KQ7, QP13, and VN10 were effective in inhibiting CE after simulated gastrointestinal digestion, especially with a significant increase in the inhibitory activity of KQ7 and RK7, respectively. Our findings suggested that bioactive peptides from yak milk cheese represented a novel class of potential CE inhibitors. Full article

The intestinal microbiome is important for synthesising nutrients, breaking down polysaccharides, protecting against foreign microbes, and aiding immune system development by producing short-chain fatty acids (SCFAs). SCFAs are formed through the interaction between the gut microbiota and the diet in the gut lumen. This study aims to extract exopolysaccharide (EPS) from the gut isolate Proteus mirabilis DMTMMR-11, a probiotic species which was optimised to improvise the yield of EPS through one-factor-at-a-time (OFAT) and response surface methodology. The central composite design (CCD) increased the yield up to 2.32 ± 0.4 g/L, abd characterization was performed to study the structural and functional moieties of EPS by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) for proton and carbon (¹H and C¹³-NMR). The EPS was subjected to artificial simulated gastrointestinal digestion by mimicking the gut conditions of healthy humans. These data reveal the higher concentrations of SCFA derivatives such as propionate, acetate, and other bioactive metabolites. The in vitro experiments in IBD (irritable bowel syndrome) patients’ gut homogenates were treated with EPS digest with SCFA, revealing that dysbiosis is reinstated, by improvising the colonisation of probiotic and gut symbionts by inhibiting the growth of pathogenic bacteria, which was studied by the metagenomic sequencing (V₃–V₄) region of the 16S rRNA gene. The EPS digest with SCFA was subjected to biological activities such as scavenging and reducing power, which showed 32.03 ± 0.21 and 13.04 ± 0.3 µg/mL. The anti-diabetic activity, like α-amylase, α-glucosidase and DPP-IV, was studied, expressing reduced IC₅₀ values at (9.21 ± 0.3, 4.43 ± 0.4, 21.4 ± 0.33) µg/mL. Anti-inflammatory activity was higher up to 75%, and the anti-lipidemic inhibition property expressed inhibition up to 40% in cholesterol esterase and pancreatic lipase. These results indicate that EPS digest with SCFA is a beneficial substrate and can be administered for combinational IBD therapies. Full article

Misgurnus anguillicaudatus (loach) is a widely distributed benthic fish in Asia. In this study, the alkaline protease was used to hydrolyze loach, and the hydrolysate products of different molecular weights were obtained by membrane separation. In vitro antioxidant assays showed that the <3 kDa fraction (SLH-1) exhibited the strongest antioxidant activity (DPPH, hydroxyl radical and superoxide radical scavenging ability, and reducing power), while SLH-1 was purified by gel filtration chromatography, and peptide sequences were identified by LC-MS/MS. A total of six peptides with antioxidant activity were identified, namely SERDPSNIKWGDAGAQ (D-1), TVDGPSGKLWR (D-2), NDHFVKL (D-3), AFRVPTP (D-4), DAGAGIAL (D-5), and VSVVDLTVR (D-6). In vitro angiotensin-converting enzyme (ACE) inhibition assay and pancreatic cholesterol esterase (CE) inhibition assay, peptide D-4 (IC50 95.07 μg/mL, 0.12 mM) and D-2 inhibited ACE, and peptide D-2 (IC50 3.19 mg/mL, 2.62 mM), D-3, and D-6 acted as pancreatic CE inhibitors. The inhibitory mechanisms of these peptides were investigated by molecular docking. The results showed that the peptides acted by binding to the key amino acids of the catalytic domain of enzymes. These results could provide the basis for the nutritional value and promote the type of healthy products from hydrolyzed loach. Full article

A rat model of disordered lipid metabolism was established to study the regulation of lipid metabolism and inflammatory response by Lactobacillus rhamnosus hsryfm 1301 fermented milk. The results showed that the high-fat diet caused the disorder of lipid metabolism in rats, accompanied by the occurrence of an inflammatory response. After Lactobacillus rhamnosus hsryfm 1301 fermented milk intervention, the blood lipid level was reduced along with the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as triglyceride (TG) and total cholesterol (TC) contents in the liver of rats (p < 0.05), the fat vacuoles of rat hepatocytes were reduced, and the lipid accumulation in the rat liver was decreased. Liver injury was restored. Meanwhile, the levels of free fatty acid (FFA) and fatty acid synthase (FAS), acetyl coenzyme A carboxylase (ACC), lipoprotein esterase (LPL) and hepatic lipase (HL) in serum and liver of rats were significantly lower than those in the model group (p < 0.05), which indicated that fatty acid synthesis was inhibited, fatty acid production was reduced and lipid metabolism was restored to balance. In addition, the levels of reactive oxygen species (ROS) and inflammatory factors in the serum of rats were also significantly reduced (p < 0.05), and the inflammatory response of rats was restored. Lactobacillus rhamnosus hsryfm 1301 fermented milk could not only inhibit fatty acid synthase but reduce the production of excessive fatty acids, thus reducing fat accumulation, restoring the balance of lipid metabolism and alleviating the inflammatory response in rats. At the same time, it can also reduce the level of ROS through the antioxidant effect, alleviate the inflammatory response, and thus alleviate the disorder of lipid metabolism. Full article

Chronic inflammation plays a side effect on tissue regeneration, greatly inhibiting the repair or regeneration of tissues. Conventional local delivery of anti-inflammation drugs through physical encapsulation into carriers face the challenges of uncontrolled release. The construction of an inflammation-responsive prodrug to release anti-inflammation drugs depending on the occurrence of inflammation to regulate chronic inflammation is of high need. Here, we construct nanofiber-based scaffolds to regulate the inflammation response of chronic inflammation during tissue regeneration. An inflammation-sensitive prodrug is synthesized by free radical polymerization of the indomethacin-containing precursor, which is prepared by the esterification of N-(2-hydroxyethyl) acrylamide with the anti-inflammation drug indomethacin. Then, anti-inflammation scaffolds are constructed by loading the prodrug in poly(ε-caprolactone)/gelatin electrospun nanofibers. Cholesterol esterase, mimicking the inflammation environment, is adopted to catalyze the hydrolysis of the ester bonds, both in the prodrug and the nanofibers matrix, leading to the generation of indomethacin and the subsequent release to the surrounding. In contrast, only a minor amount of the drug is released from the scaffold, just based on the mechanism of hydrolysis in the absence of cholesterol esterase. Furthermore, the inflammation-responsive nanofiber scaffold can effectively inhibit the cytokines secreted from RAW264.7 macrophage cells induced by lipopolysaccharide in vitro studies, highlighting the great potential of these electrospun nanofiber scaffolds to be applied for regulating the chronic inflammation in tissue regeneration. Full article

The major polyphenols in grape seed have been shown to have beneficial health effects in the prevention of dyslipidemia and cardiovascular diseases. In this present study, we investigated the cholesterol-lowering activity of three major polyphenolic compounds found in grape seed. The results showed that gallic acid, catechin, and epicatechin significantly inhibited pancreatic cholesterol esterase in a concentration-dependent manner. Moreover, they bound to taurocholic acid, taurodeoxycholic acid, and glycodeoxycholic acid at levels ranging from 38.6% to 28.2%. At the concentration of 0.2 mg/mL, gallic acid, catechin, and epicatechin reduced the formation of cholesterol micelles 27.26 ± 2.17%, 11.88 ± 0.75%, and 19.49 ± 3.71%, respectively. These findings clearly demonstrate that three major polyphenolic compounds present in a particular grape seed have cholesterol-lowering activity by inhibiting pancreatic cholesterol esterase, binding of bile acids, and reducing solubility of cholesterol in micelles which may result in delayed cholesterol absorption. Full article