Evaluation of the effects of ivermectin and Moringa oleifera nanoparticles on muscular trichinellosis in a murine model

Abstract

The parasitic nematode Trichinella spiralis ( T. spiralis ) offers a rich experimental model in the study of muscle inflammation and regeneration. The larval stage of the parasite is a particularly challenging drug target due to its encystation inside the sophisticated nurse cell complex. Non-conventional pharmacological approaches such as herbal remedies and nanoformulations have garnered special research attention in the management of T. spiralis -induced myositis. The current study investigated the effects of Moringa oleifera nanoparticles (MON) and Ivermectin nanoparticles (IVN) on T. spiralis muscle larvae and their potential effect on signaling molecules involved in cellular regeneration and proinflammatory immune response inside infected muscle fibers. Thirty Swiss albino mice were divided into five groups, each containing 6 mice: Uninfected untreated (negative) control group; T. spiralis -infected untreated group; T. spiralis -infected group treated with IVN; T. spiralis -infected group treated with MON; T. spiralis -infected group treated with both IVN and MON. Assessment of the parasitic burden and histopathological examination of skeletal muscles were performed. In addition, the local immunohistochemical expression of nuclear factor-kappa B (NF-κB) in skeletal muscles was evaluated. Moreover, the local gene expression of insulin-like growth factor (IGF) and its downstream anabolic switch phosphatidyl inositol 3-kinase (PI3K) was analyzed. The combined treatment regimen demonstrated superior efficacy compared to monotherapies. It resulted in the most significant reduction in parasitic burden, restoration of muscle tissue histological architecture, and the most pronounced downregulation of the transcription regulator NF-κB. Moreover, the gene expression of IGF and PI3K was modulated by both the single and combined therapy of IVN and MON. These findings suggest that nanoformulations of ivermectin and Moringa oleifera may represent potential antiparasitic adjuvants against T. spiralis larvae. Furthermore, the observed improvements in muscle tissue repair appear to correlate with a modulation of the local inflammatory environment and the potential upregulation of markers involved in cellular regeneration and anabolic processes. • Nanoparticles of ivermectin and Moringa oleifera decrease Trichinella spiralis larval burden in skeletal muscle. • Both drugs improve muscle histopathology and reduce inflammation. • Ivermectin and Moringa nanoparticles reverse the significant increase in NF-κB expression induced by Trichinella spiralis infection. • Both agents modulate IGF and PI3K gene expression, suggesting a potential impact on muscle regeneration of infected muscles. • The anti-parasitic, anti-inflammatory and myogenic effects of both ivermectin and Moringa nanoformulations promote them as effective adjuvants in the treatment of muscular trichinellosis.