MyMedR

Displaying all 6 publications

Abstract:

Sort:

Fulltext Multifunctional Tyrosinase Inhibitor Peptides with Copper Chelating, UV-Absorption and Antioxidant Activities: Kinetic and Docking Studies

Yap PG, Gan CY

Foods, 2021 Mar 22;10(3).
PMID: 33810046 DOI: 10.3390/foods10030675

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 (IC50 = 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 FeSO4), 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.
Tyrosinase inhibitory peptides: Structure-activity relationship study on peptide chemical properties, terminal preferences and intracellular regulation of melanogenesis signaling pathways

Yap PG, Gan CY

Biochim Biophys Acta Gen Subj, 2024 Jan;1868(1):130503.
PMID: 37923180 DOI: 10.1016/j.bbagen.2023.130503

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.
Allantoin, a Potential Metabolite That Promotes AMPK Phosphorylation and Suppresses Cholesterol Biosynthesis Via the Mevalonate Pathway and Bloch Pathway

Yap PG, Choi SB, Liong MT

Appl Biochem Biotechnol, 2020 May;191(1):226-244.
PMID: 32125649 DOI: 10.1007/s12010-020-03265-2

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.
Camel Milk-Derived Bioactive Peptides and Diabetes: Molecular View and Perspectives

Ayoub MA, Yap PG, Mudgil P, Khan FB, Anwar I, Muhammad K, et al.

J Dairy Sci, 2023 Sep 12.
PMID: 37709024 DOI: 10.3168/jds.2023-23733

In dairy science, camel milk (CM) constitutes a center of interest for scientists due to its known beneficial impact 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 molecule(s) 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 (i) insulin receptor signaling and glucose uptake, (ii) the pancreatic β-cell structure and function, and (iii) 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.
Microwave-assisted extraction of polysaccharide from Cinnamomum cassia with anti-hyperpigmentation properties: Optimization and characterization studies

Al-Ajalein AAS, Shafie MH, Yap PG, Kassim MA, Naharudin I, Wong TW, et al.

Int J Biol Macromol, 2023 Jan 31;226:321-335.
PMID: 36502951 DOI: 10.1016/j.ijbiomac.2022.12.023

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.
Fulltext Molecular docking studies on α-amylase inhibitory peptides from milk of different farm animals

Mudgil P, Al Dhaheri MKO, Alsubousi MSM, Khan H, Redha AA, Yap PG, et al.

J Dairy Sci, 2024 May;107(5):2633-2652.
PMID: 38101739 DOI: 10.3168/jds.2023-24118

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-IC50 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-IC50 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.