Exploitation of Marine-Derived Robust Biological Molecules to Manage Inflammatory Bowel Disease

Abstract

Naturally occurring biological entities with extractable and tunable structural and functional characteristics, along with therapeutic attributes, are of supreme interest for strengthening the twenty-first-century biomedical settings. Irrespective of ongoing technological and clinical advancement, traditional medicinal practices to address and manage inflammatory bowel disease (IBD) are inefficient and the effect of the administered therapeutic cues is limited. The reasonable immune response or invasion should also be circumvented for successful clinical translation of engineered cues as highly efficient and robust bioactive entities. In this context, research is underway worldwide, and researchers have redirected or regained their interests in valorizing the naturally occurring biological entities/resources, for example, algal biome so-called "treasure of untouched or underexploited sources". Algal biome from the marine environment is an immense source of excellence that has also been demonstrated as a source of bioactive compounds with unique chemical, structural, and functional features. Moreover, the molecular modeling and synthesis of new drugs based on marine-derived therapeutic and biological cues can show greater efficacy and specificity for the therapeutics. Herein, an effort has been made to cover the existing literature gap on the exploitation of naturally occurring biological entities/resources to address and efficiently manage IBD. Following a brief background study, a focus was given to design characteristics, performance evaluation of engineered cues, and point-of-care IBD therapeutics of diverse bioactive compounds from the algal biome. Noteworthy potentialities of marine-derived biologically active compounds have also been spotlighted to underlying the impact role of bio-active elements with the related pathways. The current review is also focused on the applied standpoint and clinical translation of marine-derived bioactive compounds. Furthermore, a detailed overview of clinical applications and future perspectives are also given in this review.

Keywords: algal biome; bioactive entities; engineered cues; inflammatory bowel disease; polysaccharides; therapeutic attributes.

Figure 1

Initial workup of a patient suspected of having inflammatory bowel disease (IBD). The initial workup is ideally started by the referring physician, with the subspecialist performing anything missing plus endoscopies and small bowel assessment(s) [1]. License Number: 5022881429496. Abbreviations: CBC (Complete Blood Count), CRP (C-reactive protein), ESR (Erythrocyte Sedimentation Rate), MRI (Magnetic resonance imaging), and CT (computed tomography).

Figure 2

Pathophysiology of Ulcerative Colitis. Impairment of tight junctions and the mucous layer leads to increased permeability of the intestinal epithelium, resulting in more uptake of luminal antigens. Antigen presenting cells (APC) become activated upon recognizing non-pathogenic bacteria (commensal microbiota) through Toll-like receptors (TLRs). Activated APC initiate differentiation of naïve CD4+ T-cells into Th-2 effector cells (which produce pro-inflammatory cytokines such as TNF-α, IL-5, IL-6, and IL-13). TNF-α and IL-1 activate nuclear factor κB (NF-κB) pathway, which facilitate expression of pro-inflammatory and cell survival genes. Binding of integrin-α4β7 bearing T cells to the mucosal adhesion molecule MAdCAM-1 facilitate entry of more T cells into the lamina propria. Recruitment of circulating leucocytes due to the upregulation of inflammatory chemokines (chemokine ligands: CXCL1, CXCL3, CXCL8 and CXCL10) perpetuates the inflammatory cycle. MAdCAM-1, mucosal addressin cell adhesion molecule-1; IL, interleukin; TNF-α, tumor necrosis factor-alpha; TGF-β, transforming growth factor-beta; NKT, natural killer T; DC, dendritic cell; Th, T helper; GATA3, GATA binding protein 3; IRF4, interferon regulatory factor 4; PU.1, purine-rich PU-box binding protein; FOXP3, Forkhead box protein 3. Reprinted from Ref. [4] with permission under the Creative Commons Attribution (CC BY) license. Copyright © 2020 the authors. Licensee MDPI, Basel, Switzerland.

Figure 3

Pathophysiology in Crohn’s disease. The uptake of luminal microflora stimulates APCs (e.g., dendritic cells and macrophages) which in turn produce proinflammatory cytokines such as TNF-α, IL-6, and IL-23. Activated APCs facilitate subsequent differentiation of naïve CD4⁺ T-cells into Th1 and Th17 via expression of master transcription factors. Inside the high endothelial venule, binding of α4β7-bearing lymphocytes to MAdCAM-1 causes entry of more T cells into the lamina propria. IFN-γ, interferon-gamma; FOXP3, Forkhead box protein 3; RORγt, retinoic acid receptor-related orphan nuclear receptor gamma. Reprinted from Ref. [4] with permission under the Creative Commons Attribution (CC BY) license. Copyright © 2020 the authors. Licensee MDPI, Basel, Switzerland.

Figure 4

Preparation and characterization of 6-shogaol loaded polymeric nanoparticles, (A) Schematic illustration of process through which PLGA/PLA-PEG-FA nanoparticles [NPs-PEG-FA] were fabricated using a versatile single-step surface-functionalising technique, (B) The morphology of PLGA/PLA-PEG nanoparticles [NPs-PEG] was characterised by transmission electron microscopy [TEM], and their size and zeta potential were measured by dynamic light scattering [DLS] using a Malvern Zetasizer Nano ZS90 Apparatus, and (C) The morphology, size, and zeta potential of PLGA/PLA-PEG-FA [NPs-PEG-FA] were characterized. Reprinted from Ref. [66] with permission from Oxford University Press. Copyright © 2017, Oxford University Press. License Number: 5022890402536. Abbreviations: PVA (Polyvinyl alcohol), PLGA (poly(lactic-co-glycolic acid)), PLA (Polylactic acid), PEG (Polyethylene glycol), FA (Folic acid), and NPs (Nanoparticles).

Figure 5

Schematic representation of air liquid interface of human colon carcinoma cell line (CaCo-2) equivalent epithelium in Transwell system. In the central insert, an enlarged view of the cell monolayer grown on the microporous membrane. On the right, the oral nano-delivery system consisting of oil-in-water (O/W) nanoemulsion coated with a thiolated glycol chitosan. Reprinted from Ref. [78] with permission from Elsevier. Copyright © 2018 Elsevier B.V. License Number: 5022890619360.

Figure 6

Schematic illustration of orally administered cell-specific nanotherapeutics for IBD. Reprinted from Ref. [111] with permission under the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license. Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc.

Figure 7

Mesalamine polymeric conjugate for controlled release. Reprinted from Ref. [124] with permission from Elsevier. Copyright © 2017 Elsevier B.V. License Number: 5022891040345.