RETRACTED ARTICLE: Suppression of NF-κB signaling by ECN in an arthritic model of inflammation

BMC Complementary Medicine and Therapies

卷:22

Research

Zia ur rehman¹  Sajjad Ahmad²  Feng Wang³  Li Zhang³  Fakhar ud Din⁴  Chang Hu Li⁵  Amna Khan⁶  Adnan Khan⁶  Salman Khan⁶  Bushra Shal⁶  Ashraf Ullah Khan⁷ 

[1] Department of Chemistry, Quaid-I-Azam University, 45320, Islamabad, Pakistan;

[2] Department of Health and Biological Sciences, Abasyn University, 25000, Peshawar, Pakistan;

[3] Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, People’s Republic of China;

[4] Department of Pharmacy, Faculty of Biological Sciences, Quad-i-Azam University, Islamabad, Pakistan;

[5] Division of Radiation Physics, Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China;

[6] Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan;

[7] Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan;Faculty of Pharmaceutical Sciences, Abasyn University, Peshawar, KPK, Pakistan;

关键词: Arthritis;    Lipopolysaccharide;    Immunomodulation;    Inflammation;    Oxidative stress;   

DOI  :  10.1186/s12906-022-03629-7

 received in 2021-09-17, accepted in 2022-05-19,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid isolated from the Tussilago farfara Linneaus (Asteraceae), was evaluated against acute Carrageenan and chronic complete Freund’s adjuvant (CFA)-induced arthritis in mice.MethodsAcute and chronic arthritis were induced by administering Carrageenan and CFA to the intraplantar surface of the mouse paw. Edema, mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia were assessed in the paw. Similarly, histological and immunohistological parameters were assessed following arthritis induced by CFA. Antioxidants, inflammatory cytokines, and oxidative stress markers were also studied in all the treated groups.ResultsThe ECN treatment significantly attenuated edema in the paw and elevated the nocifensive threshold following induction of this inflammatory model. Furthermore, ECN treatment markedly improved the arthritis index and distress symptoms, while attenuating the CFA-induced edema in the paw. ECN treatment also improved the histological parameters in the paw tissue compared to the control. At the same time, there was a significant reduction in edema and erosion in the ECN-treated group, as measured by radiographic analysis. Using the Comet’s assay, we showed that ECN treatment protected the DNA from chronic CFA-induced arthritis. Immunohistochemistry analysis showed a marked decrease in the expression level of p-JNK (phosphorylated C-Jun N-terminal kinase), NF-κB (Nuclear factor-kappa B), COX-2 (Cyclooxygenase-2), and TNF-α (Tumour necrosis factor-alpha) compared to the CFA-treated group. Biophysical analysis involving molecular docking, molecular dynamics simulations, and binding free energies of ECN were performed to explore the underlying mechanism.ConclusionECN exhibited significant anti-inflammatory and anti-arthritic activity against Carrageenan and CFA-induced models.

【 授权许可】

CC BY   
© The Author(s) 2022

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