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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1466057
This article is part of the Research Topic Herbal Medicines and Their Metabolites as Therapeutic Agents in Osteolytic Disease Management View all 5 articles

Neoandrographolide Inhibits Mature Osteoclast Differentiation to Alleviate Bone Loss and Treat Osteoporosis

Provisionally accepted
WEI DENG WEI DENG 1*Kai Tang Kai Tang 1Zhiying Huang Zhiying Huang 1Simin Chen Simin Chen 1Zilin Zhu Zilin Zhu 1Shukun Lin Shukun Lin 1Lubin Zhong Lubin Zhong 1Quanxin Zheng Quanxin Zheng 1Wenhua Zhao Wenhua Zhao 2Zhida Zhang Zhida Zhang 3Ling Mo Ling Mo 1
  • 1 Guangzhou University of Chinese Medicine, Guangzhou, China
  • 2 The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
  • 3 Department of Endocrinology, The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Abstract: Background: Osteoporosis(OP), as the prevalent systemic metabolic bone disease worldwide, progresses insidiously and slowly. The clinical discomfort and complications associated with OP impose a significant burden on patients. Therefore, finding more effective treatments for OP remains an urgent challenge. Method: We first conducted in vitro experiments to determine whether Neoandrographolide (NEO) exhibits cytotoxic or proliferative effects on bone marrow macrophages (BMMs) and to explore the specific timeframe during which NEO exerts its inhibitory action on osteoclast (OC) differentiation. Through Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot analysis, we examined the relative expression levels of genes and proteins associated with OC differentiation like CTSK,c-Fos,MMP9,NFATc1, and verified the underlying mechanisms. Finally, we performed in vivo experiments to further investigate the inflammation. Results: NEO exhibits no significant cytotoxic effects on BMMs at concentrations less than or equal to 30 μM while exerting inhibitory effects on OC differentiation during its early and middle stages. RT-PCR and Western Blot results reveal that NEO suppresses the expression of genes and proteins including CTSK,c-Fos,MMP9,NFATc1. Western Blot findings also indicate that NEO inhibits the phosphorylation of ERK, P38, JNK, and P65 but does not reverse the degradation of IκB-α. Additionally, NEO affects the phosphorylation of proteins in the PI3K/AKT, GSK3β, and PPARγ signaling pathways, demonstrating that NEO can inhibit OC formation through multiple pathways and targets. In vivo experiments further validated the in vitro findings by constructing an OP model, showing that NEO can mitigate bone loss induced by OC differentiation. Conclusion: NEO has the potential to serve as a therapeutic agent for OP by inhibiting the formation of mature OC through various signaling pathways.

    Keywords: Neoandrographolide, Osteoclastogenesis, MAPK, NF-κB, PI3K/AKT, PPARγ, GSK3β BMMs, bone marrow macrophages, FBS, fetal bovine serum, M-CSF, Macrophage-Stimulating Factor, BV/TV, bone volume/tissue volume, OP, osteoporosis, OB, osteoblast, OC, osteoclast, Specific pathogen free (SPF)

    Received: 17 Jul 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 DENG, Tang, Huang, Chen, Zhu, Lin, Zhong, Zheng, Zhao, Zhang and Mo. 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: WEI DENG, Guangzhou University of Chinese Medicine, Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.