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The SRC/NF-κB-AKT/NOS3 Axis as a Key Mediator of Kaempferol’s Protective Effects against Oxidative Stress-induced Osteoclastogenesis
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  • Jiaming Shen,
  • Chunjie Hu,
  • Yuelong Wang,
  • Yiying Tan,
  • Xiaochen Gao,
  • Nanxi Zhang,
  • Jingwei Lv,
  • JIaming Sun
Jiaming Shen
Jilin Province Ginseng Science Research Institute
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Chunjie Hu
First Affiliated Hospital to Changchun University of Chinese Medicine
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Yuelong Wang
Jilin Province Ginseng Science Research Institute
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Yiying Tan
Jilin Province Ginseng Science Research Institute
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Xiaochen Gao
Jilin Province Ginseng Science Research Institute
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Nanxi Zhang
Jilin Province Ginseng Science Research Institute
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Jingwei Lv
Jilin Province Ginseng Science Research Institute
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JIaming Sun
Jilin Province Ginseng Science Research Institute

Corresponding Author:sun_jiaming2000@163.com

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Abstract

Abstract: Osteoclasts are integral to the advancement of osteoporosis (OP), and their generation under conditions of oxidative stress (OS) involves various pathways. However, the specific mechanism through which the natural antioxidant kaempferol (KAE) mitigates the influence of OS on osteoclasts remains somewhat uncertain. In order to evaluate the effect of KAE on osteoclast formation under OS and explore its possible mechanism. In this study, zebrafish were used to observe the effects of KAE on OP and OS. OP and OS ”double disease targets” network pharmacology were used to predict the action target and mechanism of KAE on OP under OS. The effects of KAE on osteoclast differentiation induced by OS were evaluated using RWA264.7 cells induced by LPS. To elucidate the potential mechanism, in order to clarify its possible mechanism, the expression of related factors and target genes during induction was detected. Result: The presence of KAE exhibited potential in improving the conditions of OP and OS in zebrafish. KAE can reduce the OS of RAW 264.7 cells stimulated by LPS, inhibit the formation of osteoclasts, and change the level of related factors of OS, and reduce the increase of TRAP. The utilization of network pharmacology and target gene expression assay revealed that KAE exerted a down-regulatory effect on the expression of proto-oncogene tyrosine protein kinase (SRC), nuclear factor kappa-B (NF-κB), Serine/Threonine Kinase-1 (AKT1), Nitric Oxide Synthase 3 (NOS3) and Matrix Metallopeptidase-2 (MMP2). Based on these findings, it can be concluded that KAE may effectively mitigates OS and impedes the formation of osteoclasts through the SRC/NF-κB-AKT/NOS3 axis.
29 May 2024Submitted to Immunity, Inflammation and Disease
29 May 2024Submission Checks Completed
29 May 2024Assigned to Editor
01 Jun 2024Reviewer(s) Assigned
30 Aug 2024Review(s) Completed, Editorial Evaluation Pending
01 Sep 2024Editorial Decision: Revise Major
10 Sep 20241st Revision Received
11 Sep 2024Submission Checks Completed
11 Sep 2024Assigned to Editor
11 Sep 2024Review(s) Completed, Editorial Evaluation Pending
17 Sep 2024Reviewer(s) Assigned
01 Oct 2024Editorial Decision: Accept