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Updated: Aug 11, 2026

Murine Model of Epicutaneously-Induced Immunomodulation
Published on: June 24, 2025
Effects of Eucommia ulmoides Oliv. on Key Nodes and Gene Expression in Wnt/β-Catenin Pathway in Collagen-Induced
Tian-Qi Jia1, Ruo-Yan Yang1, Ying-Yuan Chen1
1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Objective:
To investigate the therapeutic mechanisms of Eucommia ulmoides Oliv. (EC) in a collagen-induced arthritis (CIA) rat model.
Methods:
The CIA model was established by immunizing rats with type II collagen. Wistar rats were assigned to the normal group (n=6), and the remaining model rats were further divided by body weight into the CIA model, EC, and Iguratimod (IGU) positive control groups (n=6 per group). EC (4 g/kg per day) and IGU (4.5 mg/kg daily) was administered orally for 4 weeks. Arthritis severity was evaluated by measuring hind paw volume. Histopathological analysis of ankle joints was performed using hematoxylin and eosin (HE) and safranin O/fast green. Serum levels of procollagen type I N-terminal propeptide (PINP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), osteocalcin (BGP), β-crosslaps (β-CTX), tumor necrosis factor (TNF-α), interleukin (IL)-1β, and CTNNB1 (β-catenin) were measured by ELISA. Serum nitric oxide (NO) levels were measured using a nitrate reductase assay. Transcriptomic sequencing and RT-qPCR were performed to assess mRNA expression, and Western blot was used to assess protein expression of Wnt2 and β-catenin in the spleen.
Results:
Compared with the CIA group, EC significantly alleviated arthritis severity and paw swelling (P<0.05) and reduced synovial inflammation and cartilage damage. Serum analysis showed that EC decreased TNF-α, IL-1β, NO, ICTP, and β-CTX, while increasing PINP and BGP (P<0.05 or P<0.01), and also reduced CTNNB1 (P<0.01) compared with the CIA group. In the spleen, EC reduced mRNA expressions of IL-1β, IL-6, and TNF-α (P<0.05 or P<0.01), upregulated IL-10, and decreased β-catenin protein (P<0.05); Wnt2 mRNA showed a non-significant downward trend compared with the CIA group. In the ankle joints, EC significantly reduced mRNA expressions of Wnt2 and β-catenin (P<0.05 or P<0.01).
Conclusions:
EC may alleviate inflammation and bone destruction in RA by regulating the Wnt/β-catenin signaling pathway, suggesting its potential as a therapeutic agent for RA.
