Bacterial cellulose nanocrystal as drug delivery system for overcoming the biological barrier of cyano-phycocyanin: a biomedical application of microbial product.

Phycocyanin, produced by Spirulina platensis, has been reported as an anti-inflammatory, anti-hyperalgesia, antioxidant, anti-tumor, and anti-cancer agent. However, the ingestion of phycocyanin in the body is often hindered by its instability against gastric pH conditions. The nano-drug delivery system has developed as a promising platform for efficient drug delivery and improvement as well as drug efficacy. Bacterial cellulose nanocrystal (BCNC) has it superiority as DDS due to its inherent properties such as nanoscale dimension, large surface area, - biocompatibility, and non-toxic. To improve its mechanical properties, BCNC was crosslinked with glutaraldehyde and was analyzed as a potential candidate for DDS. The Fourier transform infrared analysis of the BCNC suggested that hydrolysis did not alter the chemical composition. The index of crystallinity of the BCNC was 18.31% higher than that of the original BC, suggesting that crystalline BC has been successfully isolated. The BCNC particle also showed a needle-like morphology which is 25 ± 10 nm in diameter and a mean length of 626 ± 172 nm. Crosslinked BCNC also had larger pores than the original BCNC along with higher thermal stability. Optimum phycocyanin adsorption on crosslinked BCNC reached 65.3% in 3 h. The release study shows that the crosslinked BCNC can protect the phycocyanin retardation by gastric fluid until phycocyanin reaches the targeted sites. This study provides an alternative potential DDS derived from natural bioresources with less expenses and better properties to promote the application of BCNC as functional nanomaterials in biomedical science.

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.

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.