Valorization of Salmo salar Skin Waste for the Synthesis of Angiotensin Converting Enzyme-1 (ACE1) Inhibitory Peptides.

One of potential inhibitors which is widely used for the clinical treatment of COVID-19 in comorbid patients is Angiostensin Converting Enzyme-1 (ACE1) inhibitor. A safer peptide-based ACE1 inhibitor derived from salmon skin collagen, that is considered as the by-product of the fish processing industry have been investigated in this study. The inhibitory activity against ACE1 was examined using in vitro and in silico methods. In vitro analysis includes the extraction of acid-soluble collagen, characterization using FTIR, Raman, UV-Vis, XRD, cytotoxicity assay, and determination of inhibition against ACE1. In silico method visualizes binding affinity, molecular interaction, and inhibition type of intact collagen and active peptides derived from collagen against ACE1 using molecular docking. The results of FTIR spectra detected amide functional groups (A, B, I, II, III) and imine proline/hydroxyproline, while the results of Raman displayed peak absorption of amide I, amide III, proline/hydroxyproline ring, phenylalanine, and protein backbone. Furthermore, UV-Vis spectra showed typical collagen absorption at 230 nm and based on XRD data, the chain types in the samples were α-helix. ACE1 inhibition activity was obtained in a concentration-dependent manner where the highest was 82.83% and 85.84% at concentrations of 1000, and 2000 µg/mL, respectively, and showed very low cytotoxicity at the concentration less than 1000 µg/mL. In silico study showed an interaction between ACE1 and collagen outside the active site with the affinity of - 213.89 kcal/mol. Furthermore, the active peptides of collagen displayed greater affinity compared to lisinopril, namely HF (His-Phe), WYT (Trp-Tyr-Thr), and WF (Trp-Phe) of - 11.52; - 10.22; - 9.58 kcal/mol, respectively. The salmon skin-derived collagen demonstrated ACE1 inhibition activity with a non-competitive inhibition mechanism. In contrast, the active peptides were predicted as potent competitive inhibitors against ACE1. This study indicated that valorization of fish by-product can lead to the production of a promising bioactive compound to treat COVID-19 patient with diabetic comorbid.

Synthesis, modification and application of fish skin gelatin-based hydrogel as sustainable and versatile bioresource of antidiabetic peptide.

Gelatin hydrogel is widely employed in various fields, however, commercially available gelatin hydrogels are mostly derived from mammalian which has many disadvantages due to the supply and ethical issues. In this study, the properties of hydrogels from fish-derived collagen fabricated with varying Glutaraldehyde (GA) determined. The antidiabetic properties of salmon gelatin (SG) and tilapia gelatin (TG) was also evaluated against α-glucosidase. Glutaraldehyde-crosslinked salmon gelatin and tilapia gelatin were used, and compared with different concentrations of GA by 0.05 %, 0.1 %, and 0.15 %. Water absorbency, swelling, porosity, pore size and water retention of the hydrogels were dependent on the degree of crosslinking. The synthesis of hydrogels was confirmed by FTIR study. Scanning electron microscope (SEM) observation showed that all hydrogels have a porous structure with irregular shapes and heterogeneous morphology. Performance tests showed that gelatin-GA 0.05 % mixture had the best performance. Antidiabetic bioactivity in vitro and in silico tests showed that the active peptides of SG and TG showed a high binding affinity to α-glucosidase enzyme. In conclusion, SG and TG cross-linked GA 0.05 % have the potential as an antidiabetic agent and as a useful option over mammalian-derived gelatin.

In silico proteolysis and molecular interaction of tilapia (Oreochromis niloticus) skin collagen-derived peptides for environmental remediation.

Fish skin collagen hydrolyzate has demonstrated the potent inhibition of dipeptidyl peptidase-IV (DPP-IV), one of the treatments for type-2 diabetes mellitus (type-2 DM), but the precise mechanism is still unclear. This study used in silico method to evaluate the potential of the active peptides from tilapia skin collagen (Oreochromis niloticus) for DPP-IV inhibitor. The methodology includes collagen hydrolysis using BIOPEP, which is the database of bioactive peptides; active peptide selection; toxicity, allergenicity, sensory analysis of active peptides; and binding of active peptides to DPP-IV compared with linagliptin. The result indicated that in silico enzymatic hydrolysis of collagen produced active peptides with better prediction of biological activity than intact collagen. There are 13 active peptides were predicted as non-toxic and non-allergenic, some of which have a bitter, salty, and undetectable taste. Docking simulations showed all active peptides interacted with DPP-IV through hydrogen bonds, van der Waals force, hydrophobic interaction, electrostatic force, π-sulfur, and unfavorable interaction, where WF (Trp-Phe), VW (Val-Trp), WY (Trp-Tyr), and WG (Trp-Gly) displayed higher binding affinities of 0.8; 0.5; 0.4; and 0.3 kcal/mol compared with linagliptin. In this study, we successfully demonstrated antidiabetic type-2 DM potential of the active peptides from tilapia skin collagen. The obtained data provided preliminary data for further research in the utilization of fish skin waste as a functional compound to treat the type-2 DM patients. Alternatively, this treatment can be synergistically combined with the available antidiabetic drugs to improve the insulin secretion of the type-2 DM patients.

Microalgae as a potential sustainable solution to environment health.

Cyanobacteria such as Spirulina platensis secretes numerous biomolecules while consuming CO2 for photosynthesis which can reduce the environmental pollution as it can also be grown in wastewater. These biomolecules can be further processed in numerous pathways such as feed, fuel, pharmaceuticals, and nutraceuticals. This study aims to screen the potential molecular mechanisms of pigments from cyanobacteria as antidiabetic type-2 candidates through molecular docking. The activities of the test compounds were compared to commercial diabetic drugs, such as acarbose, linagliptin and polydatin. The results indicated that the binding affinity of pheophytin, ß-carotene, and phycocyanobilin to α-amylase were 0.4, 2, and 2.6 kcal/mol higher than that of acarbose with α-amylase. Binding affinity between pheophytin, ß-carotene, and phycocyanobilin with α-glucosidase were found to be comparable, which resulted 1.2, and 1.6 kcal/mol higher than that of acarbose with α-glucosidase. Meanwhile, binding activity of ß-carotene and phycocyanobilin with DPP-IV were 0.5 and 0.3 kcal/mol higher than that of linagliptin with DPP-IV, whereas pheophytin, ß-carotene, and phycocyanobilin with Glucose-6-phosphate dehydrogenase (G6PD) were 0.2, 1, and 1.4 kcal/mol higher from that of polydatin with G6PD. Moreover, pheophytin, ß-carotene and phycocyanobilin were likely to inhibit α-amylase, α-glucosidase, and DPP-IV competitively, while uncompetitively for G6PD. Thus, the integration of molecular docking and experimental approach, such as in vitro and in vivo studies may greatly improve the discovery of true bioactive compounds in cyanobacteria for type 2 diabetes mellitus drugs and treatments.