Anti-Inflammatory Effects of Helminth-Derived Products: Potential Applications and Challenges in Diabetes Mellitus Management

Abstract

The global rise in diabetes mellitus (DM), particularly type 2 diabetes (T2D), has become a major public health challenge. According to the "hygiene hypothesis", helminth infections may offer therapeutic benefits for DM. These infections are known to modulate immune responses, reduce inflammation, and improve insulin sensitivity. However, they also carry risks, such as malnutrition, anemia, and intestinal obstruction. Importantly, helminth excretory/secretory products, which include small molecules and proteins, have shown therapeutic potential in treating various inflammatory diseases with minimal side effects. This review explores the anti-inflammatory properties of helminth derivatives and their potential to alleviate chronic inflammation in both type 1 diabetes and T2D, highlighting their promise as future drug candidates. Additionally, it discusses the possible applications of these derivatives in DM management and the challenges involved in translating these findings into clinical practice.

Keywords: anti-inflammatory; diabetes mellitus; helminth-derived products; immune modulation.

Figure 1

Estimated age-adjusted comparative prevalence of diabetes.

Figure 2

Helminth proteins regulate immune responses by modulating DCs and Tregs. Initially, helminth proteins are identified by pattern recognition receptors on the surface of host epithelial cells, which trigger specific signaling pathways, notably TLR2 and TLR4. This interaction activates NF-κB and interferon regulatory factors (IRF1 and IRF4), crucial for driving the expression of anti-inflammatory cytokines like IL-10 and TGF-β. Once released into the surrounding environment, these cytokines bind to their respective receptors, IL-10R and TGF-β receptors, on DCs. This binding modulates DC functions, facilitating the activation and proliferation of regulatory Treg cells. These Treg cells are essential for maintaining immune tolerance and preventing overactive immune responses, thereby playing a pivotal role in the immune system’s ability to manage parasitic infections effectively. Created in BioRender. Yunhuan Zhu (2025) https://BioRender.com/x98w137.

Figure 3

Common drug delivery systems. Oral administration involves lipid nanoparticles, which deliver drugs such as curcumin. These particles are ingested and enter the stomach. In the case of transdermal administration, drug-laden gels, such as those containing meloxicam, employ microneedles to administer drug particles through the skin. For intravenous administration, drugs like methotrexate are loaded into polyamidoamine (PAMAM) dendrimers, which are then injected directly into the bloodstream. Recently, innovative methods using nanomaterials for drug delivery have been developed, including releasing drugs controlled by various external stimuli such as light, heat, pH, oxygen, and magnetic fields. These new approaches offer precise control over when and where drugs are released, enhancing treatment effectiveness and reducing potential side effects. Created in BioRender. Yunhuan Zhu (2025) https://BioRender.com/p89w615.

Figure 4

Comparison of protein glycosylation patterns in different biological systems. In the plant section, a specific glycosylation pattern can be seen by transferring T-DNA containing the Bacillus thuringiensis (Bt) gene into plant cells and regenerating plants. The types of glycosylation expressed by proteins are also shown in yeast, insects, and mammals (such as CHO and HEK293 cells). Created in BioRender. Yunhuan Zhu (2025) https://BioRender.com/l22b252.