Plant Heteropolysaccharides as Potential Anti-Diabetic Agents: A Review

Abstract

Diabetes mellitus (DM), a chronic metabolic disease, poses a significant challenge to global health. Although type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and other types of diabetes mellitus differ in pathological mechanisms, they converge in that hyperglycemia is a universal clinical hallmark. Currently, the antidiabetic medications employed in clinical practice for blood glucose management require long-term administration and are associated with various side effects that can adversely impact human health. Plant heteropolysaccharides have emerged as promising candidates for anti-diabetic therapy, owing to their abundant natural sources, absence of toxicities, and confirmed hypoglycemic activities. This review aims to summarize the anti-diabetic mechanisms of plant heteropolysaccharides by dissecting the key biological pathways associated with clinical intervention in DM, including the modulation of insulin secretion, a reduction in insulin resistance, and an alteration in the composition of the gut microbiota. For these reasons, these findings provide a theoretical framework for the clinical application of plant heteropolysaccharides and indicate that they are expected to become natural agents used in treating DM.

Keywords: anti-diabetic agent; diabetes mellitus; gut microbiota; insulin resistance; mechanisms; plant heteropolysaccharides.

Figure 1

The regulation of pancreatic β-cells by plant heteropolysaccharides. This figure illustrates how plant heteropolysaccharides preserve pancreatic β-cells and the insulin secretory capacity in diabetes mellitus (DM) management. The relevant mechanisms are described as follows. Apoptosis inhibition: Plant heteropolysaccharides reduce pancreatic β-cells apoptosis by regulating the balance between pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2. Promotion of proliferation: Plant heteropolysaccharides stimulate pancreatic β-cells regeneration, which is critical for maintaining insulin production. Antioxidant enhancement: Plant heteropolysaccharides enhance the activity of antioxidant enzymes (such as superoxide dismutase [SOD] and catalase [CAT]) and reduce malondialdehyde (MDA) levels, thereby protecting pancreatic β-cells from oxidative stress. PDX-1 regulation: Plant heteropolysaccharides upregulate PDX-1 (pancreatic and duodenal homeobox 1), a transcription factor essential for insulin gene expression and pancreatic β-cells function.

Figure 2

Improvement in insulin resistance by plant heteropolysaccharides. Plant heteropolysaccharides improve insulin resistance through the following mechanisms: activating insulin signaling pathways related to insulin receptor substrate 1/phosphatidylinositol 3-kinase/protein kinase B (IRS1/PI3K/AKT) and AMP-activated protein kinase (AMPK) pathways, triggering nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant defense pathways, inhibiting nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and reducing lipid accumulation.

Figure 3

Modulation of the gut microbiota by plant heteropolysaccharides. Plant heteropolysaccharides exert their anti-diabetes mellitus (DM) effects by regulating the gut microbiota, a process that involves the enrichment of beneficial bacteria and a reduction in pathogenic bacteria.