Biochemical and biophysical research communications · 2025
Mechanistic insights into the anti-rheumatoid arthritis effects of ursolic acid from Periploca forrestii Schltr. via network pharmacology, molecular docking, and experimental Validation.
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Wu Xiaoqian, Teng Kangdi, He Yanjun, Cai Xu, Zhu Jiaxin, Han Lingfei, Feng Feng, Liu Wenyuan, Qu Wei
Аннотация
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis and systemic inflammation. Periploca forrestii Schltr., one of the "three treasures of Miao medicine", is traditionally used for RA treatment due to its reputed effects in relaxing tendons, activating collaterals, and dispelling wind and dampness. This study investigates the mechanisms by which Ursolic Acid (UA), a triterpenoid from Periploca forrestii, exerts anti-inflammatory effects in treating RA.
METHODS: Network pharmacology was used to identify potential targets of UA in RA treatment by integrating data from the Traditional Chinese Medicine System Pharmacology (TCMSP) Database, PubChem, and SwissTargetPrediction. Key targets were refined through protein-protein interaction (PPI) network analysis, and relevant signaling pathways were identified via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was employed to validate the predicted interactions. The anti-inflammatory efficacy of UA was assessed in vitro using an LPS-induced RAW264.7 macrophage model and in vivo using a collagen-induced arthritis (CIA) rat model.
RESULTS: A total of 15 key targets were identified, primarily involved in inflammation response, cell proliferation and apoptosis, and bone resorption and remodeling. GO and KEGG enrichment analyses highlighted the TNF signaling pathway as a central mechanism. In vitro experiments demonstrated that UA significantly inhibited the production of inflammatory mediators, including NO, TNF-α, IL-6, and MMP9, and reduced intracellular reactive oxygen species (ROS) levels in LPS-induced RAW264.7 cells. In the CIA rat model, UA markedly decreased joint swelling, arthritis scores, articular erosion, and TNF-α and IL-6 levels in spleen and serum.
CONCLUSION: Our findings suggest that UA exerts therapeutic effects on RA by modulating key inflammatory pathways, particularly the TNF signaling pathway. This study highlights the potential of UA as a therapeutic agent for RA and provides a pharmacological basis for the traditional use of P. forrestii in RA management, thus supporting the development of ethnopharmacological approached in modern medicine.
METHODS: Network pharmacology was used to identify potential targets of UA in RA treatment by integrating data from the Traditional Chinese Medicine System Pharmacology (TCMSP) Database, PubChem, and SwissTargetPrediction. Key targets were refined through protein-protein interaction (PPI) network analysis, and relevant signaling pathways were identified via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was employed to validate the predicted interactions. The anti-inflammatory efficacy of UA was assessed in vitro using an LPS-induced RAW264.7 macrophage model and in vivo using a collagen-induced arthritis (CIA) rat model.
RESULTS: A total of 15 key targets were identified, primarily involved in inflammation response, cell proliferation and apoptosis, and bone resorption and remodeling. GO and KEGG enrichment analyses highlighted the TNF signaling pathway as a central mechanism. In vitro experiments demonstrated that UA significantly inhibited the production of inflammatory mediators, including NO, TNF-α, IL-6, and MMP9, and reduced intracellular reactive oxygen species (ROS) levels in LPS-induced RAW264.7 cells. In the CIA rat model, UA markedly decreased joint swelling, arthritis scores, articular erosion, and TNF-α and IL-6 levels in spleen and serum.
CONCLUSION: Our findings suggest that UA exerts therapeutic effects on RA by modulating key inflammatory pathways, particularly the TNF signaling pathway. This study highlights the potential of UA as a therapeutic agent for RA and provides a pharmacological basis for the traditional use of P. forrestii in RA management, thus supporting the development of ethnopharmacological approached in modern medicine.