ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Bone Research
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1639261
This article is part of the Research TopicBone Aging and Osteoporosis: Recent Evidence Focusing on Plant-Based Natural Products - Volume IIView all 6 articles
Lang-chuang-ding Restores Bone Homeostasis in Systemic Lupus Erythematosus associated Osteoporosis by Targeting NF-κB Signaling: A Network Pharmacology and Experimental Study
Provisionally accepted
- 1The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China
- 2Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China
- 3Guangzhou University of Chinese Medicine, Guangzhou, China
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Systemic lupus erythematosus (SLE) is frequently associated with secondary osteoporosis (OP), substantially compromising patients' quality of life. Although Lang-chuang-ding (LCD), a traditional Chinese medicine formulation, has demonstrated efficacy in suppressing SLE progression, its therapeutic potential for SLE-associated OP remains uninvestigated. This study investigated the therapeutic effects and underlying pharmacological mechanisms of LCD on SLE-associated OP through in vivo experimental validation using MRL/lpr mouse model in conjunction with network pharmacology analysis. Our findings demonstrated that LCD significantly attenuated bone loss in the distal femur by improving bone morphometric parameters, including bone mineral density (BMD), trabecular number (Tb.N), and trabecular bone separation (Tb.Sp), while simultaneously suppressing osteoclast activity and promoting osteogenesis. Network pharmacological analysis identified 63 overlapping targets among LCD components, SLE-related genes, and OP-associated targets, with inflammatory mediators TNF-α, IL-6, and IL-1β emerging as pivotal hub targets. KEGG enrichment analysis revealed significant NF-κB pathway enrichment among the core therapeutic targets. Experimental validation demonstrated that LCD effectively suppressed inflammatory responses by markedly reducing pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 expression while simultaneously inhibiting NF-κB pathway activation through downregulation of p-IκB, P65, and p-P65 in the distal femur. Collectively, these findings demonstrate that LCD effectively ameliorates SLE-associated OP through modulation of inflammatory cytokine networks and the NF-κB signaling pathway, establishing its therapeutic potential as a mechanism-based intervention for SLE-associated OP.
Keywords: SLE-associated Osteoporosis, Lang-chuang-ding, Bone homeostasis, inflammatory cytokines, Mechanism
Received: 01 Jun 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Luo, Zhou, Shen, Zeng and Ruan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hongfeng Ruan, Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China
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