Looking at Marine-Derived Bioactive Molecules as Upcoming Anti-Diabetic Agents: A Special Emphasis on PTP1B Inhibitors

Abstract

Diabetes mellitus (DM) is a chronic metabolic disease with high morbimortality rates. DM has two types: type 1, which is often associated with a total destruction of pancreatic beta cells, and non-insulin-dependent or type 2 diabetes mellitus (T2DM), more closely associated with obesity and old age. The main causes of T2DM are insulin resistance and/or inadequate insulin secretion. Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in T2DM, as its overexpression may induce insulin resistance. Thus, since PTP1B may be a therapeutic target for both T2DM and obesity, the search for novel and promising natural inhibitors has gained much attention. Hence, several marine organisms, including macro and microalgae, sponges, marine invertebrates, sea urchins, seaweeds, soft corals, lichens, and sea grasses, have been recently evaluated as potential drug sources. This review provides an overview of the role of PTP1B in T2DM insulin signaling and treatment, and highlights the recent findings of several compounds and extracts derived from marine organisms and their relevance as upcoming PTP1B inhibitors. In this systematic literature review, more than 60 marine-derived metabolites exhibiting PTP1B inhibitory activity are listed. Their chemical classes, structural features, relative PTP1B inhibitory potency (assessed by IC50 values), and structure–activity relationships (SARs) that could be drawn from the available data are discussed. The upcoming challenge in the field of marine research—metabolomics—is also addressed.

Molecular Mechanism of Functional Ingredients in Barley to Combat Human Chronic Diseases

“…Antidiabetic Properties. Diabetes is a chronic metabolic disease with high mortality rates; therefore, search for novel natural inhibitors has gained much attention [81]. Major antidiabetic elements in barley are β-glucan, phenolic compounds (phenolic acids and flavonoids), phytosterols, tocols, arabinoxylan, and resistant starch ( Table 2).…”

Bioactive Properties of Marine Phenolics

“…Due to its ubiquity in the insulin-targeted tissues and its role in insulin resistance development [ 142 ], inhibition of PTP1B activity would be a target for the treatment of T2DM and obesity. Ezzat et al [ 171 ] reviewed the in vitro studies focused on evaluating the inhibitory activity of PTP1B marine polyphenols. Xu et al [ 172 ] studied the inhibitory activity of a marine-derived bromophenol compound (3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(ethoxymethyl)benzyl)benzene- 1,2-diol) isolated from the red alga Rhodomela confervoides in insulin-resistant C2C12 myotubes.…”

Phytopharmacological Strategies in the Management of Type 2 Diabetes Mellitus

“…Isoderrone, derrone, alpinumisoflavone, and mucusisoflavone isolated from ethanol-water extract of Ficus racemosa exhibit inhibitory activity against PTP1B with IC 50 values of 22.7 ± 1.7, 12.6 ± 1.6, 21.2 ± 3.8, and 2.5 ± 0.2 µM, respectively [61]. Ezzat and colleagues reviewed marine-derived bioactive molecules as PTP1B inhibitors where they mentioned this activity in sulfircin (sesterpene sulfate) isolated from deep-water sponge Ircinia, bromophenols from red algae Rhodomela confervoides (IC 50 from 0.8 to 4.5 µM), two bromophenols from Indonesian marine sponge Lamellodysidea herbacea (IC 50 0.9 and 1.7 µM), and others from red algae Symphyocladia latiuscula (IC 50 3.9, 4.3 and 2.7 µM) [62]. Other compounds mentioned in this review include brominated metabolites from red algae Laurencia similis, polybromodiphenyl ether derivatives from marine sponge Lamellodysidea herbacea, eckol, and its derivatives isolated from brown algae Ecklonia stolonifera and Eisenia bicyclis [62].…”