Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates DSS-induced colitis by inhibiting ERK/NF-κB activation in macrophages

作者：Jiao Liu, Danye Niu, Yu Tang, Ruoheng Zheng, Yinyin Qin, Xiuqin Cheng, Shubo Pan, Jinfei Yuan, Xiaohua Shi, Jiao Yang · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156492 · 被引用次数：13 · 研究领域：Diet and metabolism studies、Muscle metabolism and nutrition、Metabolism and Genetic Disorders

BACKGROUND: β-Hydroxy β-Methylbutyrate (HMB), derived from leucine, is known for its role in anti-oxidation and anti-inflammation. But, the application of HMB in IBD treatment is not fully understood, highlighting the requirement for further research. PURPOSE: We aimed to examine the effects of HMB treatment on DSS-induced chronic colitis in mice and explore its underlying mechanisms. METHODS: To simulate colonic inflammation, a murine colitis model was generated by using DSS induction. Critical indicators such as body weight, colon length, disease activity index (DAI), and gross pathology were thoroughly monitored. Immunohistochemistry assay was conducted to assess the expression of Occludin and F4/80. Flow cytometry was employed to evaluate the expression levels of CD80 and CD86. qPCR was performed to measure cytokine expression (IL-6, IL-1β, TNF-α, IL-22, CXCL2, iNOS). RNA sequencing was carried out using bone-marrow derived dendritic macrophage cells (BMDMs). RESULTS: Our study indicates that HMB treatment substantially mitigated colonic damage in murine models of DSS-induced colitis, highlighting its anti-inflammatory potential. Notably, HMB significantly enhanced the expression of Occludin in these mice. Furthermore, HMB downregulated proinflammatory markers such as IL-6, IL-1β, and TNF-α as well as CXCL2 in the colon tissue. In vitro experiments also revealed that HMB reduced production of proinflammatory cytokines induced by DSS and suppressed the expression levels of...