Neuropeptides in Immunometabolism and Neuroinflammation: Insights from Traditional Chinese Medicine.

Abstract

Neuropeptides are small bioactive peptides secreted by neurons and immune cells that serve as critical messengers in both central and peripheral systems. Recent studies have identified key neuropeptides-such as Substance P (SP), Vasoactive Intestinal Peptide (VIP), Neuropeptide Y (NPY), and Calcitonin Gene-Related Peptide (CGRP)-as pivotal regulators of immunometabolism and neuroinflammation. These peptides influence macrophage polarization, T cell differentiation, cytokine production, and neuroimmune crosstalk, linking chronic inflammation to conditions such as obesity, diabetes, autoimmunity, and neurodegeneration. This review synthesizes emerging evidence on Traditional Chinese Medicine (TCM) interventions-including herbal formulas, single herbs, bioactive compounds, and acupuncture-that modulate neuropeptide signaling via NF-κB, MAPK, and Nrf2 pathways. These mechanisms contribute to analgesia, emotional stabilization, metabolic regulation, and neuroprotection. The article further presents a modular framework connecting representative Chinese medicinal substances to specific neuropeptides and physiological functions, offering a translational foundation for neuropeptide-targeted therapies and integrative precision health strategies.