Letter to the Editor: Salidroside in ulcerative colitis - neuroimmune regulatory mechanisms and clinical translation prospects

Abstract

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with a complex and incompletely understood pathogenesis. Although current first-line therapies, including 5-aminosalicylic acid, corticosteroids, and immunosuppressants, effectively control acute inflammation, their long-term use is limited by steroid dependence, increased susceptibility to opportunistic infections, drug resistance, and failure to maintain sustained remission. Salidroside, a natural bioactive compound, has recently emerged as a promising therapeutic candidate owing to its anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. We read with great interest the study by Li et al demonstrated that salidroside attenuates intestinal inflammation and promotes intestinal mucosal barrier repair by activating the cyclic adenosine monophosphate (cAMP)-protein kinase A -cAMP response element-binding protein signaling pathway while suppressing the pathological activation of enteric glial cells (EGCs). Building on these findings, this editorial highlights the therapeutic potential of salidroside from the perspective of the enteric neuro-glial-immune regulatory network, emphasizing the pivotal role of EGCs in UC pathogenesis. Furthermore, we discuss how salidroside may alleviate intestinal inflammation by modulating EGC activation, preserving intestinal immune homeostasis, restoring mucosal barrier integrity, and regulating neuro-immune interactions. Finally, we summarize the current challenges and future directions for the clinical translation of salidroside in UC, providing a theoretical basis for the development of EGC-targeted therapeutic strategies and facilitating the future clinical translation of salidroside.

Keywords: Ulcerative colitis; Salidroside; Cyclic adenosine monophosphate pathway; Protein Kinase A pathway; cAMP response element-binding protein pathway; Enteric glial cells; Neuro-glial-immune regulatory network

Core Tip: This article presents a novel perspective based on the “enteric neuro-glial-immune regulatory network” and elucidates the potential mechanisms by which salidroside exerts anti-inflammatory, immunomodulatory, and intestinal mucosal barrier-protective effects through the regulation of enteric glial cells. Furthermore, by discussing the challenges associated with clinical translation and formulation optimization strategies, this article explores the potential application of salidroside as a multi-target therapeutic agent for precision treatment of ulcerative colitis.