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已发表论文
基于 OPG/RANK/RANKL/P38 MAPK 信号通路的广藿香醇对实验性牙周炎大鼠的作用及机制
Authors Zhang S, Duan F, He T, Sun C, Zhen M, Liang E, Liu X, Dai Y, Zhan R, Hu N, Xia Y, Liu S
Received 26 March 2025
Accepted for publication 27 August 2025
Published 13 September 2025 Volume 2025:18 Pages 12599—12617
DOI https://doi.org/10.2147/JIR.S530534
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Renan Dal Fabbro
Shuting Zhang,1,* Feifei Duan,1,* Tianzhen He,1 Chaoqun Sun,1 Menglu Zhen,1 Enxi Liang,1 Xingduo Liu,1 Yuqiong Dai,1 Ruoting Zhan,2,3 Nianchun Hu,4 Yun Xia,5 Sijun Liu1
1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Key Laboratory of Chinese Medicinal Resource From Lingnan, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Department of Neurology, 921 Hospital of the Joint Logistics Support Force, Changsha, People’s Republic of China; 5Luohu District Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Sijun Liu, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Waihuan Road, Guangzhou Higher Education Mega Center, No. 232, Guangzhou, Guangdong, 510006, People’s Republic of China, Email liusijun@gzucm.edu.cn Yun Xia, Department of Nephropathy, Department of Nephropathy, Luohu District Traditional Chinese Medicine Hospital, Shenzhen Luohu district, Xiantong road 16, CN 518004, Guangdong, China, Email 1595633489@qq.com
Background: Patchouli has been used for a long time in traditional Chinese medicine to treat inflammatory diseases, and its main active component, patchouli alcohol (PA), also has anti-inflammatory effects. However, the underlying molecular mechanism of PA in the periodontitis treatment is not well understood.
Aim of the Study: The primary objective of this study was to examine the effects of PA on experimental periodontitis in rats through the lens of the OPG/RANK/RANKL/p38 MAPK signaling pathway.
Materials and Methods: A rat model of periodontitis induced by ligation combined with LPS injection was used to evaluate the therapeutic effects of PA on periodontitis. Target prediction, target screening, intersection target identification, protein-protein interaction (PPI) network construction and topological analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, along with molecular docking were employed to predict the potential pharmacological mechanisms of PA. Micro-CT was utilized to detect alveolar bone loss, ELISA was used to measure inflammation, and qRT-PCR and Western blot were performed to further confirm its mechanisms of action.
Results: Network pharmacology indicated that the p38 MAPK signaling pathway is the primary mechanism by which PA treats periodontitis. PA treatment reduced the distance between the cementum and the alveolar bone crest in rats with periodontitis. ELISA and H&E staining results showed that PA alleviated the inflammatory response and reduced the levels of IL-6, TNF-α, and IL-1β. qRT-PCR analysis revealed that PA significantly increased the mRNA expression levels of RUNX2 and OPG, and decreased the mRNA expression levels of RANK, RANKL, NFATc1, and TRAF6. Western blot revealed that PA significantly reduced the expression of RANKL, RANK, and MMP9 while significantly elevating OPG expression.
Conclusion: PA is an effective therapeutic strategy for periodontitis, and its mechanism of action involves inhibiting alveolar bone loss and modulating the OPG/RANK/RANKL/p38 MAPK pathway.
Keywords: network pharmacology, molecular docking, periodontitis, patchouli alcohol, inflammation, alveolar bone loss
1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Key Laboratory of Chinese Medicinal Resource From Lingnan, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Department of Neurology, 921 Hospital of the Joint Logistics Support Force, Changsha, People’s Republic of China; 5Luohu District Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Sijun Liu, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Waihuan Road, Guangzhou Higher Education Mega Center, No. 232, Guangzhou, Guangdong, 510006, People’s Republic of China, Email liusijun@gzucm.edu.cn Yun Xia, Department of Nephropathy, Department of Nephropathy, Luohu District Traditional Chinese Medicine Hospital, Shenzhen Luohu district, Xiantong road 16, CN 518004, Guangdong, China, Email 1595633489@qq.com
Background: Patchouli has been used for a long time in traditional Chinese medicine to treat inflammatory diseases, and its main active component, patchouli alcohol (PA), also has anti-inflammatory effects. However, the underlying molecular mechanism of PA in the periodontitis treatment is not well understood.
Aim of the Study: The primary objective of this study was to examine the effects of PA on experimental periodontitis in rats through the lens of the OPG/RANK/RANKL/p38 MAPK signaling pathway.
Materials and Methods: A rat model of periodontitis induced by ligation combined with LPS injection was used to evaluate the therapeutic effects of PA on periodontitis. Target prediction, target screening, intersection target identification, protein-protein interaction (PPI) network construction and topological analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, along with molecular docking were employed to predict the potential pharmacological mechanisms of PA. Micro-CT was utilized to detect alveolar bone loss, ELISA was used to measure inflammation, and qRT-PCR and Western blot were performed to further confirm its mechanisms of action.
Results: Network pharmacology indicated that the p38 MAPK signaling pathway is the primary mechanism by which PA treats periodontitis. PA treatment reduced the distance between the cementum and the alveolar bone crest in rats with periodontitis. ELISA and H&E staining results showed that PA alleviated the inflammatory response and reduced the levels of IL-6, TNF-α, and IL-1β. qRT-PCR analysis revealed that PA significantly increased the mRNA expression levels of RUNX2 and OPG, and decreased the mRNA expression levels of RANK, RANKL, NFATc1, and TRAF6. Western blot revealed that PA significantly reduced the expression of RANKL, RANK, and MMP9 while significantly elevating OPG expression.
Conclusion: PA is an effective therapeutic strategy for periodontitis, and its mechanism of action involves inhibiting alveolar bone loss and modulating the OPG/RANK/RANKL/p38 MAPK pathway.
Keywords: network pharmacology, molecular docking, periodontitis, patchouli alcohol, inflammation, alveolar bone loss