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Network Pharmacology and Experimental Validation of a Securidaca inappendiculata Xanthone Fraction Targeting
Xuan Chen1,2, Bingru Fan1,2, Ting Wang1,2
1Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Wannan Medical College, Wuhu, 241002, China.
Background:
Securidaca inappendiculata is a traditional medicinal plant used for the treatment of Rheumatoid Arthritis (RA) and related inflammatory conditions, and it possesses significant anti-RA activity. However, the precise molecular mechanisms underlying its therapeutic effects remain to be fully elucidated.
Aim:
This study aimed to elucidate the therapeutic mechanisms of a Xanthone-enriched Fraction (XRF) from S. inappendiculata against RA by integrating network pharmacology with experimental validation.
Methods:
Using both an Adjuvant-Induced Arthritis (AIA) rat model and an LPS/IFN-γ- stimulated THP-1 macrophage model, an integrated strategy was implemented. Potential targets and pathways for the xanthones were predicted via network pharmacology and molecular docking. Thereafter, the anti-arthritic efficacy of the xanthone fraction was evaluated in vivo, while its pro-apoptotic effect and regulation of key signaling pathways were investigated in vitro.
Results:
XRF significantly alleviated joint swelling and synovial inflammation in AIA rats. Mechanistically, it inhibited the PI3K/AKT/mTOR/HIF-1α signaling cascade and reduced phosphorylation of GSK-3β at Ser9, thereby promoting the apoptosis of pro-inflammatory M1 macrophages.
Discussion:
This work elucidated the anti-RA mechanism of S. inappendiculata: eight xanthones acted on the PI3K/AKT/mTOR/HIF-1α/GSK-3β axis to induce M1 macrophage apoptosis, validating the integrated approach and laying groundwork for RA treatment and natural product research.
Conclusion:
The present study provides a scientific foundation for further elucidating the mechanisms of S. inappendiculata against RA.
