Mechanistic Insights into the Immunomodulatory Effects of Velvet Antler Peptides from Sika Deer

Background Sika deer antler is a traditional Chinese medicine, and its mechanism of action on immune regulation is still unclear. Therefore, this study aims to explore its related mechanism. Objectives To investigate the mechanism by which velvet antler peptides (VAPs) from Sika deer regulate immune function in mice through the toll-like receptors 2 (TLR2)/toll-like receptors 4 (TLR4) and tumor necrosis factor-alpha (TNF-α)/interleukin-3 (IL-3)/recombinant cytotoxic T-lymphocyte-associated-antigen-4 (CTLA-4) signaling pathways. Materials and Methods Male ICR mice were randomly divided into five groups: blank control (BC), positive control (PC), low dose (LD, 60 mg/kg), medium dose (MD, 120 mg/kg), and high dose (HD, 180 mg/kg). The BC group was administered saline for 1 week, while the other groups received dexamethasone (25 mg/kg) for 1 week. The BC and PC groups were gavaged with distilled water, while the experimental groups were gavaged with different doses of VAPs. After 21 days, serum levels of immunoglobulin M (IgM), immunoglobulin G (IgG), T lymphocyte CD8+ (CD8+), TNF-α, and spleen gene expression levels of TLR2, TLR4, TNF-α, IL-3, and CTLA-4 were measured. Results Compared to the PC group, mice in the LD, MD, and HD groups exhibited a significant increase in body weight. Enzyme-linked immunosorbent assay (ELISA) results showed that TNF-α levels in the serum were significantly decreased, while IgM, IgG, and CD8+ levels were significantly increased in the LD, MD, and HD groups. Gene expression analysis revealed that TNF-α levels were significantly decreased, and IL-3 and CTLA-4 levels were significantly increased in the spleen of the LD, MD, and HD groups compared to the PC group. Additionally, the expression levels of TLR2 and TLR4 were significantly elevated. Conclusion VAPs improve immune status in mice by modulating the expression of TLR2/TLR4 and TNF-α/IL-3/CTLA-4 signaling pathways, revealing the underlying mechanism of their immunoregulatory effects.