2. Academic Validation
  3. Luteolin attenuates Talaromyces marneffei-induced bone destruction by alleviating NLRP3-mediated osteoblast pyroptosis via TNF-α/NF-κB pathway inhibition

Luteolin attenuates Talaromyces marneffei-induced bone destruction by alleviating NLRP3-mediated osteoblast pyroptosis via TNF-α/NF-κB pathway inhibition

  • Cell Signal. 2026 May:141:112392. doi: 10.1016/j.cellsig.2026.112392.
Fayun Yang 1,  Xiaoming Peng 2,  Weilun Zhao 3,  Yi Zhang 1,  Yilin Teng 1,  Jianhua Huang 4,  Baicheng Wan 1,  Shaohui Zong 5,  Gaofeng Zeng 6
Affiliations

Affiliations

  • 1 Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China.
  • 2 Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China; Department of Joint and Bone Diseases, Yuebei People's Hospital, Affiliated Hospital of Shantou University, Shao Guan 512000, China.
  • 3 Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China; Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning 530000, China.
  • 4 Wuming Hospital of Guangxi Medical University, Nanning 530000, China.
  • 5 Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Nanning 530000, China; Wuming Hospital of Guangxi Medical University, Nanning 530000, China. Electronic address: [email protected].
  • 6 School of Public Health of Guangxi Medical University, Nanning 530000, China. Electronic address: [email protected].
PMID: 41605374 DOI: 10.1016/j.cellsig.2026.112392
Abstract

Talaromyces marneffei (T. marneffei), an opportunistic pathogen, mainly infects immunocompromised individuals and often causes osteolytic bone destruction. We designed the current study to investigate the therapeutic efficacy and intrinsic mechanism of luteolin (Lut) on T. marneffei-associated osteolysis. The potential therapeutic targets of luteolin were identified by RNA Sequencing (RNA-Seq) and network pharmacology methods. GO (gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes), and GSEA (Gene Set Enrichment Analysis) enrichment analyses were used to reveal the molecular mechanism and related pathways. A mouse model of osteolysis induced by T. marneffei and an in vitro Infection model were employed to validate the therapeutic efficacy of Lut, and to investigate the regulatory function of Lut in osteogenesis as well as NLRP3 (NLR family pyrin domain containing 3)-mediated Pyroptosis. RNA-seq showed differential expressions of nuclear factor-kappa B (NF-κB) and NLRP3-related Pyroptosis genes after T. marneffei Infection. Network pharmacology identified tumor necrosis factor-α (TNF-α) as a key target. Enrichment analyses highlighted the roles of TNF, NF-κB, and NOD-like Receptor (NLR) signaling pathways. In vivo, Lut alleviated bone destruction by suppressing TNF-α-mediated NF-κB signaling, reducing mitochondrial damage, and alleviating NLRP3-mediated osteoblast Pyroptosis. In vitro, Lut downregulated TNF-α to inhibit NF-κB signaling, attenuated NLRP3-mediated osteoblast Pyroptosis and intracellular Reactive Oxygen Species (ROS) accumulation and promoted osteogenic capacity. In conclusion, Lut inhibits the TNF-α/NF-κB pathway to alleviate NLRP3-mediated osteoblast Pyroptosis and maintain osteogenic capacity, showing great potential in treating T. marneffei-induced bone destruction.

Keywords

Bone destruction; Luteolin; NF-κB; Pyroptosis; TNF-α; Talaromyces marneffei.

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