Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in rats

Fluoride is an essential trace element required for normal physiological functions and holds significant importance for human health. However, excessive fluoride intake can lead to renal damage, for which effective prevention and therapeutic strategies remain scarce. Astragalus polysaccharide (APS),...

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Main Authors: Xiaoyue Zhang, Qianda Yan, Yuanyuan Xiao, Xingyan Du, Xuehua Zhang, Didong Lou, Fang Peng, Daiyong Chen, Wenchao Tang
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325004452
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author Xiaoyue Zhang
Qianda Yan
Yuanyuan Xiao
Xingyan Du
Xuehua Zhang
Didong Lou
Fang Peng
Daiyong Chen
Wenchao Tang
author_facet Xiaoyue Zhang
Qianda Yan
Yuanyuan Xiao
Xingyan Du
Xuehua Zhang
Didong Lou
Fang Peng
Daiyong Chen
Wenchao Tang
author_sort Xiaoyue Zhang
collection DOAJ
description Fluoride is an essential trace element required for normal physiological functions and holds significant importance for human health. However, excessive fluoride intake can lead to renal damage, for which effective prevention and therapeutic strategies remain scarce. Astragalus polysaccharide (APS), a major bioactive component of the traditional Chinese herb Astragalus membranaceus, possesses pharmacological properties including anti-inflammatory, antiviral, and antioxidant activities. In this study, we investigated the protective effects of APS against fluoride-induced renal injury in vivo experiment. Additionally, network pharmacology and molecular docking techniques were employed to predict its potential mechanisms of action, while the protein expression levels of key target molecules were validated. The results demonstrated that APS intervention significantly alleviated renal injury and oxidative stress induced by sodium fluoride (NaF) in rats. Key targets involved in the amelioration of fluoride-induced renal damage by APS included STAT3, Caspase-3, JUN, MMP1, and PTGS2. Molecular docking analysis revealed high-affinity binding between APS and these core targets. Immunohistochemical and Western blot analysis further confirmed that APS suppressed the expression of pro-apoptotic proteins STAT3, Caspase-3, JUN, and MMP1 while enhancing the expression of the anti-apoptotic protein PTGS2. Overall, our findings suggest that APS alleviates fluoride-induced renal injury by modulating multiple targets, with the potential mechanism linked to the regulation of apoptotic processes. This study provides a theoretical basis for the prevention and treatment of fluoride toxicity.
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spelling doaj-art-7ab262962baa4ec7b169bb2d3ed4a1bc2025-08-20T01:54:18ZengElsevierEcotoxicology and Environmental Safety0147-65132025-04-0129411810910.1016/j.ecoenv.2025.118109Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in ratsXiaoyue Zhang0Qianda Yan1Yuanyuan Xiao2Xingyan Du3Xuehua Zhang4Didong Lou5Fang Peng6Daiyong Chen7Wenchao Tang8School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; School of Public Health, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; School of Public Health, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, ChinaSchool of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; School of Public Health, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China; Corresponding author at: School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.Fluoride is an essential trace element required for normal physiological functions and holds significant importance for human health. However, excessive fluoride intake can lead to renal damage, for which effective prevention and therapeutic strategies remain scarce. Astragalus polysaccharide (APS), a major bioactive component of the traditional Chinese herb Astragalus membranaceus, possesses pharmacological properties including anti-inflammatory, antiviral, and antioxidant activities. In this study, we investigated the protective effects of APS against fluoride-induced renal injury in vivo experiment. Additionally, network pharmacology and molecular docking techniques were employed to predict its potential mechanisms of action, while the protein expression levels of key target molecules were validated. The results demonstrated that APS intervention significantly alleviated renal injury and oxidative stress induced by sodium fluoride (NaF) in rats. Key targets involved in the amelioration of fluoride-induced renal damage by APS included STAT3, Caspase-3, JUN, MMP1, and PTGS2. Molecular docking analysis revealed high-affinity binding between APS and these core targets. Immunohistochemical and Western blot analysis further confirmed that APS suppressed the expression of pro-apoptotic proteins STAT3, Caspase-3, JUN, and MMP1 while enhancing the expression of the anti-apoptotic protein PTGS2. Overall, our findings suggest that APS alleviates fluoride-induced renal injury by modulating multiple targets, with the potential mechanism linked to the regulation of apoptotic processes. This study provides a theoretical basis for the prevention and treatment of fluoride toxicity.http://www.sciencedirect.com/science/article/pii/S0147651325004452FluoridesRenal injuryAstragalus polysaccharideNetwork pharmacologyMolecular DockingApoptosis
spellingShingle Xiaoyue Zhang
Qianda Yan
Yuanyuan Xiao
Xingyan Du
Xuehua Zhang
Didong Lou
Fang Peng
Daiyong Chen
Wenchao Tang
Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in rats
Ecotoxicology and Environmental Safety
Fluorides
Renal injury
Astragalus polysaccharide
Network pharmacology
Molecular Docking
Apoptosis
title Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in rats
title_full Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in rats
title_fullStr Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in rats
title_full_unstemmed Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in rats
title_short Integrating network pharmacology, molecular docking, and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride-induced renal injury in rats
title_sort integrating network pharmacology molecular docking and animal studies to investigate the protective effect of astragalus polysaccharide on fluoride induced renal injury in rats
topic Fluorides
Renal injury
Astragalus polysaccharide
Network pharmacology
Molecular Docking
Apoptosis
url http://www.sciencedirect.com/science/article/pii/S0147651325004452
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