Search

Ramie leaf polysaccharides (RLP) were extracted using deep eutectic solvent (DES) and microwave. The extraction conditions, i.e., buffer-to-substrate (B:S) ratio (10:1-30:1 w/v), microwave power (90-270 W) and extraction duration (2-4 min) were optimized using response surface methodology. Based on the optimized model, 21.1 mL/g B:S ratio, 263 W microwave power and 2.8 min extraction time had successfully produced RLP with 16.67 ± 1.10 % (w/w) yield and 80.84 ± 1.16 % 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The 23.4 ± 0.389 kDa RLP was a neutral polysaccharide with low carbohydrate, protein, and phenolic contents. The low galacturonic acid content (0.89 ± 0.05 mg/g) suggested RLP contained partially pectic-polysaccharide. The major monosaccharides of RLP were rhamnose, glucose, galactose and xylose. RLP was a relatively non-linear, highly branched polysaccharide with short branches based on the monosaccharide ratio. Bioactivity screening had identified the reduction (0.66 ± 0.02 mmol Fe 2+ /g) and copper chelation (48.5 ± 0.4 %) activities of RLP. The polysaccharide could also absorb ultraviolet (UV) in which it gave major protection against UVB with 8.7 ± 0.3 sun protection factor. These biological activities were related to specific functional groups, monosaccharide units, molecular weight and/or the neutral property of RLP. The current findings provided new insights into the antioxidant, copper chelation and sun protection benefit of RLP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bioactive peptides produced via enzymatic hydrolysis have been widely investigated for their dipeptidyl peptidase-IV (DPP-IV) inhibitory properties. However, the deficit of studies on fermentation as a means to produce DPP-IV inhibitory peptides prompted us to draw a comparative study on DPP-IV inhibitory peptides generated from cow, camel, goat, and sheep milk using probiotic fermentation. Further, peptide identification, in silico molecular interactions with DPP-IV, and ensemble docking were performed. Results suggested that goat milk consistently exhibited greater degrees of hydrolysis than other milk types. Further, Pediococcus pentosaceus (PP-957) emerged as a potent probiotic, with significantly lower median inhibitory concentration values of DPP-IV, of 0.17, 0.12, and 0.25 µg/mL protein equivalents in fermented cow, camel, and goat milk, respectively. Overall, peptides (RPPPPVAM, CHNLDELKDTR, and VLSLSQPK) exhibited strong binding affinity, with binding energies of -9.31, -9.18, and -8.9 kcal/mol, respectively, suggesting their potential role as DPP-IV inhibitors. Overall, this study offers valuable information toward antidiabetic benefits of fermented milk products via inhibition of DPP-IV., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Fermented milk (FM) is well-known to confer health-promoting benefits, particularly for managing chronic metabolic diseases. However, the specific cholesterol esterase (CE) inhibitory activities of FM produced from different animal milk sources have not been extensively explored. This study for the first time investigates the CE inhibition potential of FM derived from bovine (F&#95;BM), camel (F&#95;CM), sheep (F&#95;SM), and goat milk (F&#95;GM), each fermented with five different probiotic strains and stored for 14 days under refrigeration. Further, peptides identification was performed and in silico approaches were used to dock potent peptides with CE enzyme (PDB: 1AQL) to decipher mechanism of enzyme inhibition. Comprehensive approach of this study combined CE inhibition assays, peptide identification, and in silico molecular docking with the CE enzyme (PDB: 1AQL) to elucidate mechanisms underlying enzyme inhibition. Upon fermentation improvements in CE-inhibition (lower IC 50 values) were observed compared to non-fermented counterparts. Moreover, the CE-inhibition potency of the FM varies significantly among the milk types and probiotic strain ( p  < 0.05). Regardless of probiotic strains, CE-inhibition was more evident for F&#95;GM followed by F&#95;CM. Peptide sequencing and molecular docking studies revealed APSFSDIPNPIGSENSEKTTMPLW from F&#95;BM showed potent binding to CE's active site, while peptides from F&#95;CM, F&#95;SM, and F&#95;GM showed indirect CE-inhibitory mechanisms. These findings suggest potential anti-hypercholesteremic effects of bovine and non-bovine fermented milk, indicating their potential use in developing novel dairy products with hypolipidemic activities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s). Published by Elsevier Ltd.)

Milk-derived peptides have emerged as a popular mean to manage various lifestyle disorders such as diabetes. Fermentation is being explored as one of the faster and efficient way of producing peptides with antidiabetic potential. Therefore, in this study, an attempt was made to comparatively investigate the pancreatic α-amylase (PAA) inhibitory properties of peptides derived from milk of different farm animals through probiotic fermentation. Peptide's identification was carried out using liquid chromatography-quadrupole time-of-flight mass spectrometry and inhibition mechanisms were characterized by molecular docking. Results obtained showed a PAA-IC 50 value (the amount of protein equivalent needed to inhibit 50% of enzymes) between 2.39 and 36.1 µg protein equivalent for different fermented samples. Overall, Pediococcus pentosaceus MF000957-derived fermented milk from all animals indicated higher PAA inhibition than other probiotic derived fermented milk (PAA-IC 50 values of 6.01, 3.53, 15.6, and 10.8 µg protein equivalent for bovine, camel, goat, and sheep fermented milk). Further, molecular docking analysis indicated that camel milk-derived peptide IMEQQQTEDEQQDK and goat milk-derived peptide DQHQKAMKPWTQPK were the most potent PAA inhibitory peptides. Overall, the study concluded that fermentation derived peptides may prove useful in for managing diabetes via inhibition of carbohydrate digesting enzyme PAA., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

In dairy science, camel milk (CM) constitutes a center of interest for scientists due to its known beneficial effect on diabetes as demonstrated in many in vitro, in vivo, and clinical studies and trials. Overall, CM had positive effects on various parameters related to glucose transport and metabolism as well as the structural and functional properties of the pancreatic β-cells and insulin secretion. Thus, CM consumption may help manage diabetes; however, such a recommendation will become rationale and clinically conceivable only if the exact molecular mechanisms and pathways involved at the cellular levels are well understood. Moreover, the application of CM as an alternative antidiabetic tool may first require the identification of the exact bioactive molecules behind such antidiabetic properties. In this review, we describe the advances in our knowledge of the molecular mechanisms reported to be involved in the beneficial effects of CM in managing diabetes using different in vitro and in vivo models. This mainly includes the effects of CM on the different molecular pathways controlling (1) insulin receptor signaling and glucose uptake, (2) the pancreatic β-cell structure and function, and (3) the activity of key metabolic enzymes in glucose metabolism. Moreover, we described the current status of the identification of CM-derived bioactive peptides and their structure-activity relationship study and characterization in the context of molecular markers related to diabetes. Such an overview will not only enrich our scientific knowledge of the plausible mode of action of CM in diabetes but should ultimately rationalize the claim of the potential application of CM against diabetes. This will pave the way toward new directions and ideas for developing a new generation of antidiabetic products taking benefits from the chemical composition of CM., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Bioactive peptides have gained attention as potential alternatives to chemical-based skin lightening agents. Based on literature search, the reported articles focused mainly on the sources and preparation methods of tyrosinase inhibitory peptides and there is lacking information regarding the structure-activity relationship (SAR) between peptide property and tyrosinase inhibition. It was hypothesized that peptide properties such as hydrophobicity/hydrophilicity and the amino acid type and position/arrangement at the terminal positions could affect peptide mode of binding hence result in various degrees of tyrosinase inhibition., Methods: In this study, the sequences of 128 tyrosinase inhibitory peptides were collected from peer-reviewed articles. The hydrophobicity/hydrophilicity property and the amino acid profile of peptides at the N- and C-terminals were analyzed using bioinformatics tools. Molecular docking analysis was employed to further elucidate the roles of reactive amino acids in tyrosinase-peptide binding interactions. The peptide-regulated intracellular melanogenesis pathways were also compiled and discussed., Results: It was found that hydrophobic and/or polar neutral properties may facilitate or stabilize peptide binding with tyrosinase. Moreover, short peptides featuring a cysteine and tyrosine at the N- and C- terminal ultimate positions tend to bind to the active site of tyrosinase whereas positively charged amino acid such as arginine at the N-terminal does not favor peptide binding to tyrosinase., Conclusions: These findings provide detailed explanation on how peptide/amino acid structures are related and what function they play in tyrosinase inhibition. It could also inspire researchers to account for tyrosinase-peptide SAR and the underlying anti-melanogenesis mechanisms in formulating peptide-based treatments or strategies against skin hyperpigmentation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The anti-hyperpigmentation effect and tyrosinase inhibitory mechanism of cinnamon polysaccharides have not been reported. The current study focused on the extraction of polysaccharides from Cinnamomum cassia bark using microwave-assisted approach and optimization of the extraction process (i.e., microwave power, irradiation time and buffer-to-sample ratio) by Box-Behnken design to obtain a high yield of polysaccharides with high sun protection factor (SPF), anti-hyperpigmentation and antioxidant activities. The extracted pectic-polysaccharides had low molecular weight and degree of esterification. The optimal extraction process had polysaccharides characterized by (a) monophenolase inhibitory activity = 97.5 %; (b) diphenolase inhibitory activity = 99.4 %; (c) ferric reducing antioxidant power = 4.4 mM; (d) SPF = 6.1; (e) yield = 13.7 %. The SPF, tyrosinase inhibitory and antioxidant activities were primarily contributed by the polysaccharides. In conclusion, the polysaccharides from C. cassia could be an alternative therapeutic source for skin hyperpigmentation treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abnormal skin pigmentation commonly occurs during the wound healing process due to the overproduction of melanin. Chicken egg white (CEW) has long been used to improve skin health. Previous published works had found CEW proteins house bioactive peptides that inhibit tyrosinase, the key enzyme of melanogenesis. The current study aimed to evaluate the anti-pigmentation potential and mechanism of the CEW-derived peptide (GYSLGNWVCAAK) and hydrolysates (CEWH mono and CEWH di ), using a cell-based model. All of these peptide and hydrolysates inhibited intracellular tyrosinase activity and melanin level up to 45.39 ± 1.31 and 70.01 ± 1.00%, respectively. GYSLGNWVCAAK and CEWH di reduced intracellular cAMP levels by 13.38 ± 3.65 and 14.55 ± 2.82%, respectively; however, CEWH mono did not affect cAMP level. Moreover, the hydrolysates downregulated the mRNA expression of melanogenesis-related genes, such as Mitf , Tyr , Trp-1 and Trp-2 , but GYSLGNWVCAAK only suppressed Tyr gene expression. Downregulation of the genes may lower the catalytic activities and/or affect the structural stability of TYR, TRP-1 and TRP-2; thus, impeding melanogenesis to cause an anti-pigmentation effect in the cell. Outcomes from the current study could serve as the starting point to understand the underlying complex, multifaceted melanogenesis regulatory mechanism at the cellular level.

Nature-derived tyrosinase inhibitors are of great industrial interest. Three monophenolase inhibitor peptides (MIPs) and three diphenolase inhibitor peptides (DIPs) from a previous study were investigated for their in vitro tyrosinase inhibitory effects, mode of inhibition, copper-chelating activity, sun protection factor (SPF) and antioxidant activities. DIP1 was found to be the most potent tyrosinase inhibitor (IC 50 = 3.04 ± 0.39 mM), which could be due to the binding interactions between its aromatic amino acid residues (Y2 and D7) with tyrosinase hotspots (H85, V248, H258, H263, F264, R268, V283 and E322) and its ability to chelate copper ion within the substrate-binding pocket. The conjugated planar rings of tyrosine and tryptophan may interact with histidine within the active site to provide stability upon enzyme-peptide binding. This postulation was later confirmed as the Lineweaver-Burk analysis had identified DIP1 as a competitive inhibitor and DIP1 also showed 36.27 ± 1.17% of copper chelating activity. In addition, DIP1 provided the highest SPF value (11.9 ± 0.04) as well as ferric reducing antioxidant power (FRAP) (5.09 ± 0.13 mM FeSO 4 ), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) (11.34 ± 0.90%) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (29.14 ± 1.36%) free radical scavenging activities compared to other peptides. These results demonstrated that DIP1 could be a multifunctional anti-tyrosinase agent with pharmaceutical and cosmeceutical applications.

Active fragments (bioactive peptides) from the chicken egg white proteins were expected to exert tyrosinase inhibitory activities in which skin hyperpigmentation could be prevented. Egg white was hydrolyzed by trypsin, chymotrypsin and the combination of both enzymes. The enzyme treatments achieved >50% degree of hydrolysis (DH) at substrate-to-enzyme (S/E) ratio of 10-30 ( w / w ) and hydrolysis time of 2-5 h. A crossed D-optimal experimental design was then used to determine the optimal enzyme composition, S/E ratio and hydrolysis time in order to yield hydrolysates with strong monophenolase and diphenolase inhibitory activities. The optimized conditions 55% trypsin, 45% chymotrypsin, S/E 10:1 w / w and 2 h achieved 45.9% monophenolase activity inhibition whereas 100% trypsin, S/E 22.13:1 w / w and 3.18 h achieved 48.1% diphenolase activity inhibition. LC/MS and MS/MS analyses identified the peptide sequences and the subsequent screening had identified 7 peptides (ILELPFASGDLLML, GYSLGNWVCAAK, YFGYTGALRCLV, HIATNAVLFFGR, FMMFESQNKDLLFK, SGALHCLK and YFGYTGALR) as the potential inhibitor peptides. These peptides were able to bind to H85, H94, H259, H263, and H296 (hotspots for active residues) as well as F92, M280 and F292 (stabilizing residues) of tyrosinase based on structure-activity relationship analysis. These findings demonstrated the potential of egg white-derived bioactive peptides as skin health therapy.

This study aimed to evaluate the effect of probiotic administration on obese and ageing models. Sprague Dawley rats were subjected to high-fat diet (HFD) and injected with D-galactose to induce premature ageing. Upon 12 weeks of treatment, the faecal samples were collected and subjected to gas chromatography-mass spectrophotometry (GC-MS) analysis for metabolite detection. The sparse partial least squares discriminant analysis (sPLS-DA) showed a distinct clustering pattern of metabolite profile in the aged and obese rats administered with probiotics Lactobacillus plantarum DR7 and L. reuteri 8513d, particularly with a significantly higher concentration of allantoin. Molecular docking simulation showed that allantoin promoted the phosphorylation (activation) of adenosine monophosphate-activated kinase (AMPK) by lowering the substrate free energy of binding (FEB) and induced the formation of an additional hydrogen bond between Val184 and the substrate AMP. Allantoin also suppressed cholesterol biosynthesis by either inducing enzyme inhibition, occupying or blocking the putative binding site to result in non-spontaneous substrate binding, as in the cases of 3-hydroxy-methylglutaryl-coA reductase (HMGCR), mevalonate kinase (MVK) and lanosterol demethylase (LDM) where positive FEBs were reported. These results demonstrated the potential of allantoin to alleviate age-related hypercholesterolaemia by upregulating AMPK and downregulating cholesterol biosynthesis via the mevalonate pathway and Bloch pathway.

Objective: To introduce the Spaso technique for reducing anterior shoulder dislocation by reporting the success rate of the Spaso technique performed by junior emergency medicine residents., Design: Retrospective case series., Setting: Urban accident and emergency department., Participants: Patients with anterior shoulder dislocations., Interventions: The Spaso technique was applied by the emergency medicine residents to reduce anterior shoulder dislocation., Results: The emergency medicine residents applied the Spaso technique to reduce 16 cases of anterior dislocated shoulder during the study period. The Spaso technique was successful in 14 of 16 cases. The overall success rate was 87.5% (95% CI 60.4, 97.8%). No complications were noted., Conclusion: A new method has been introduced for reduction of anterior shoulder dislocation by reporting the experience of junior residents. The Spaso technique is simple, effective and able to be performed by single operator. Although the sample size was small, the result of the study could provide background information for planning a properly designed randomised controlled trial to evaluate the Spaso technique.