Effects of Eucommia ulmoides Oliv. on Key Nodes and Gene Expression in Wnt/β-Catenin Pathway in Collagen-Induced Arthritis Rats

JIA Tian-qi; YANG Ruo-yan; CHEN Ying-yuan; WANG Jian-ying; TAO Jia-yi; GU Zu-xi; ZHANG Lei; YUAN Ying

doi:10.1007/s11655-026-4047-6

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Effects of Eucommia ulmoides Oliv. on Key Nodes and Gene Expression in Wnt/β-Catenin Pathway in Collagen-Induced Arthritis Rats

Original Article | Updated：2026-11-13

- Effects of Eucommia ulmoides Oliv. on Key Nodes and Gene Expression in Wnt/β-Catenin Pathway in Collagen-Induced Arthritis Rats
- Chinese Journal of Integrative Medicine Vol. 32, Issue 11, Pages: 1016-1023(2026)
- Affiliations：
  
  School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
  Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
  Laboratory Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
- Author bio：
  
  Correspondence to: Prof. YUAN Ying, E-mail: yyin921@163.com
- Funds：
- DOI：10.1007/s11655-026-4047-6
  CLC：
- Accepted：08 June 2026，
  
  Published：2026-11
- Accepted：
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JIA Tian-qi, YANG Ruo-yan, CHEN Ying-yuan, et al. Effects of Eucommia ulmoides Oliv. on Key Nodes and Gene Expression in Wnt/β-Catenin Pathway in Collagen-Induced Arthritis Rats[J]. Chinese Journal of Integrative Medicine, 2026, 32(11): 1016-1023.
DOI：

JIA Tian-qi, YANG Ruo-yan, CHEN Ying-yuan, et al. Effects of Eucommia ulmoides Oliv. on Key Nodes and Gene Expression in Wnt/β-Catenin Pathway in Collagen-Induced Arthritis Rats[J]. Chinese Journal of Integrative Medicine, 2026, 32(11): 1016-1023. DOI： 10.1007/s11655-026-4047-6.

摘要

Abstract

Objective: To investigate the therapeutic mechanisms of Eucommia ulmoides Oliv. (EC) in a collageninduced 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

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

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). Conclusion: 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.

关键词

Keywords

references

Fleischmann R, Swierkot J, Penn SK, Durez P, Bessette L, Bu X, et al. Long-term safety and efficacy of upadacitinib versus adalimumab in patients with rheumatoid arthritis: 5-year data from the phase 3 randomised SELECT-COMPARE study. RMD Open 2024;10:e004007.

Zhang Q, Liu J, Zhang M, Wei S, Li R, Gao Y, et al. Apoptosis induction of fibroblast-like synoviocytes is an important molecular mechanism for herbal medicine along with its active components in treating rheumatoid arthritis. Biomolecules 2019;9:795.

Huang L, Lyu Q, Zheng W, Yang Q, Cao G. Traditional application and modern pharmacological research of Eucommia ulmoides Oliv. Chin Med 2021;16:73.

Zhao X, Wang Y, Nie Z, Han L, Zhong X, Yan X, et al. Eucommia ulmoides leaf extract alters gut microbiota composition, enhances short-chain fatty acids production, and ameliorates osteoporosis in SAMP6 model. Food Sci Nutr 2020;8:4897-4906.

Zhang Y, Wang JY, Wang H, Chen XY, Zhang L, Yuan Y. Alcohol extract of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis. Chin Med 2021;16:113.

Zhang Y, Tang LD, Wang JY, Wang H, Chen XY, Zhang L, et al. Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis. Chin J Nat Med 2022;20:458-472.

Di Matteo A, Bathon JM, Emery P. Rheumatoid arthritis. Lancet 2023;402:2019-2033.

Yan Y, Zhang LB, Ma R, Wang MN, He J, Wang PP, et al. Jolkinolide B ameliorates rheumatoid arthritis by regulating JAK2/ STAT3 pathway. Phytomedicine 2024;124:155311.

Guo D, Pan H, Lu X, Chen Z, Zhou L, Chen S, et al. Rspo2 exacerbates rheumatoid arthritis by targeting aggressive phenotype of fibroblast-like synoviocytes and disrupting chondrocyte homeostasis via Wnt/β-catenin pathway. Arthritis Res Ther 2023;25:217.

Stavre Z, Kim JM, Yang YS, Nündel K, Chaugule S, Sato T, et al. Schnurri-3 inhibition suppresses bone and joint damage in rheumatoid arthritis. Proc Natl Acad Sci USA 2023;120:e2218019120.

Nagy G, Roodenrijs NM, Welsing PM, Kedves M, Hamar A, van der Goes MC, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31-35.

Shen J, Gao Y, Deng Y, Xia Z, Wang X, He X, et al.Eucommia ulmoides extract regulates oxidative stress to maintain calcium homeostasis and improve diabetic osteoporosis. Food Sci Nutr 2024;12:8067-8083.

Wang JY, Yuan Y, Chen XJ, Fu SG, Zhang L, Hong YL, et al. Extract from Eucommia ulmoides Oliv. ameliorates arthritis via regulation of inflammation, synoviocyte proliferation and osteoclastogenesis in vitro and in vivo. J Ethnopharmacol 2016;194:609-616.

Wang H, Geng X, Ai F, Yu Z, Zhang Y, Zhang B, et al. Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance. Chin J Nat Med 2024;22:341-355.

Poutoglidou F, Pourzitaki C, Manthou ME, Samoladas E, Saitis A, Malliou F, et al. Infliximab prevents systemic bone loss and suppresses tendon inflammation in a collagen-induced arthritis rat model. Inflammopharmacology 2021;29:661-672.

Aydin S. A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides 2015;72:4-15.

Yang YJ, Lu LJ, Wang JJ, Ma SY, Xu BL, Lin R, et al. Tubson-2 decoction ameliorates rheumatoid arthritis complicated with osteoporosis in CIA rats involving isochlorogenic acid A regulating IL-17/MAPK pathway. Phytomedicine 2023;116:154875.

Li C, Zhang K, Jin X, Gao X, Lv J, Shen J, et al. A transcriptomics and network pharmacology approach to elucidate the mechanism of action of geniposide on carbon tetrachloride-induced liver injury in rats. Int Immunopharmacol 2023;120:110391.

Jin Z, Chang B, Wei Y, Yang Y, Zhang H, Liu J, et al. Curcumin exerts chondroprotective effects against osteoarthritis by promoting AMPK/PINK1/Parkin-mediated mitophagy. Biomed Pharmacother 2022;151:113092.

Li Y, Ye Q, Li J, Zhang L, Yu C, Xue S, et al. Exploring the mechanism of Taohong Siwu Decoction in treating ischemic stroke injury via the circDnajc1/miR-27a-5p/C1qc signaling axis. Phytomedicine 2025;136:156305.

Mei D, Zhang T, Liu R, Wang P, Hu L, Xu L, et al. hIgD-Fc-Ig fusion protein regulates T cell functions by inhibiting TCR signaling pathway in adjuvant arthritis rats. Int Immunopharmacol 2023;119:110154.

Fontanella RA, Ghosh P, Pesapane A, Taktaz F, Puocci A, Franzese M, et al. Tirzepatide prevents neurodegeneration through multiple molecular pathways. J Transl Med 2024;22:114.

Kondo N, Kuroda T, Kobayashi D. Cytokine networks in the pathogenesis of rheumatoid arthritis. Int J Mol Sci 2021;22:10922.

Yan J, Yang S, Han L, Ba X, Shen P, Lin W, et al. Dyslipidemia in rheumatoid arthritis: the possible mechanisms. Front Immunol 2023;14:1254753.

Jura-Póltorak A, Szeremeta A, Olczyk K, Zo -Giebel A, Komosińska-Vassev K. Bone metabolism and RANKL/OPG ratio in rheumatoid arthritis women treated with TNF-α inhibitors. J Clin Med 2021;10:2905.

Cici D, Corrado A, Rotondo C, Cantatore FP. Wnt signaling and biological therapy in rheumatoid arthritis and spondyloarthritis. Int J Mol Sci 2019;20:5552.

Wang HX, Li TY, Kidder GM. WNT2 regulates DNA synthesis in mouse granulosa cells through beta-catenin.Biol Reprod 2010;82:865-875.

Riitano G, Spinelli F, Manganelli V, Caissutti D, Capozzi A, Garufi C, et al. Wnt signaling as a translational target in rheumatoid and psoriatic arthritis. J Transl Med 2025;23:158.

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