Hesperidin methyl chalcone alleviates spinal tuberculosis in New Zealand white rabbits by suppressing immune responses

Objective: Spinal tuberculosis (ST) refers to tuberculosis resulted from infections of Mycobacterium tuberculosis ( Mtb ) in the spinal cord. Hesperidin methyl chalcone (HMC) is a flavonoid derivative from citrus fruits with anti-inflammatory properties. We aimed to investigate the efficacy of HMC in treating ST in New Zealand white rabbit model. Design and Setting: Rabbits were infected in the sixth lumbar vertebral bodies with or without Mtb strain H37Rv followed by treatments with HMC. Outcome Measures: 10 weeks post treatments, the adjacent vertebral tissues were examined by hematoxylin-eosin staining. The expression levels of transcription factor κB (NF-κB) p65 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in lymphocytes were determined using reverse transcription quantitative real-time PCR (RT-qPCR), Western blot and enzyme-linked immunosorbent assays (ELISA). The serum levels of interleukin (IL)-2, IL-4, IL-10 as well as interferon (IFN)-γ were also assessed using ELISA. Western blot was used to determine the effects of HMC on the phosphorylation of IKKα/β, p65, and IκBα in the signal transduction of NF-κB pathways. Results: HMC significantly attenuated the granulation in adjacent vertebral bone tissues. The expression of p65, IL-4, IL-10, and MCP-1 was reduced. The NF-κB pathway was suppressed, in which the phosphorylation of IκBα, IKKα/β, and p65 was inhibited whereas the relative level of IκBα was increased. Conclusion: HMC could serve as a therapeutic option to effectively inhibit granulomas formation through downregulation of MCP-1, IL-4, IL-10, and NF-κB in the treatment of ST.