Cai Xiaolong, Bai Ying, Liang Chao, Zhou Jiawei, Liu Yafeng, Guo Jianqiang, Jing Yifan, Fang Yujing, Hu Xiaofei, Wu Jing, Hu Dong
School of Medicine, Anhui University of Science and Technology, Huainan City, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, School of Medicine, Anhui University of Science and Technology, Huainan City, China.
School of Medicine, Anhui University of Science and Technology, Huainan City, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, School of Medicine, Anhui University of Science and Technology, Huainan City, China; Huainan Xinhua Medical Group Xinhua Hospital, China.
Int Immunopharmacol. 2025 Apr 24;153:114458. doi: 10.1016/j.intimp.2025.114458. Epub 2025 Mar 18.
Silicosis, a pervasive and life-threatening occupational respiratory disease, poses a substantial global health burden, particularly affecting those in impacted communities and their families. Characterized by irreversible pulmonary fibrosis, the disease's complex pathogenesis remains poorly elucidated, presenting significant challenges for therapeutic intervention. This study integrates bioinformatics, network pharmacology, and experimental validation to explore the potential mechanisms and therapeutic drugs for silicosis. Initially, differentially expressed genes (DEGs) in silicosis were subjected to GO and KEGG pathway enrichment analysis. Subsequently, the DEGs were imported into the cMap database for drug prediction, leading to the identification of piperine (PIP) as a candidate drug for the treatment of silicosis. Network pharmacology analysis then determined the pharmacological targets of PIP and demonstrated its ability to modulate the JAK2-STAT3 signaling pathway. Finally, we validated the therapeutic effects and mechanisms of PIP in silicosis. In vivo, PIP significantly ameliorated inflammation and fibrosis induced by crystalline silica (CS) in a murine model of silicosis, including inflammatory cell infiltration, formation of inflammasomes, deposition of collagen fibers and extracellular matrix, and expression of inflammatory and fibrotic factors. In vitro, PIP inhibited CS-induced cytokine expression, ROS generation, macrophage apoptosis, and activation of the JAK2-STAT3 signaling pathways. Collectively, our research identifies and validates PIP as a promising candidate for the improvement of silicosis.
矽肺是一种普遍存在且危及生命的职业性呼吸系统疾病，给全球健康带来了沉重负担，尤其影响受影响社区的人群及其家庭。该疾病以不可逆的肺纤维化为特征，其复杂的发病机制仍未完全阐明，这给治疗干预带来了重大挑战。本研究整合了生物信息学、网络药理学和实验验证，以探索矽肺的潜在机制和治疗药物。首先，对矽肺中的差异表达基因（DEGs）进行了基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。随后，将这些DEGs导入cMap数据库进行药物预测，从而确定胡椒碱（PIP）为治疗矽肺的候选药物。网络药理学分析随后确定了PIP的药理靶点，并证明其能够调节JAK2-STAT3信号通路。最后，我们验证了PIP在矽肺中的治疗效果和机制。在体内，PIP显著改善了矽肺小鼠模型中由结晶二氧化硅（CS）诱导的炎症和纤维化，包括炎症细胞浸润、炎性小体形成、胶原纤维和细胞外基质沉积以及炎症和纤维化因子的表达。在体外，PIP抑制了CS诱导的细胞因子表达、活性氧生成、巨噬细胞凋亡以及JAK2-STAT3信号通路的激活。总的来说，我们的研究鉴定并验证了PIP是改善矽肺的一个有前景的候选药物。
