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Scutellarin alleviates complete freund’s adjuvant-induced rheumatoid arthritis in mice by regulating the Keap1/Nrf2/HO-1 pathway

JIAN LI1, QINGQING WANG2, XIAOYING ZHANG1,*

1 Department of Pharmacy, The First People’s Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, 311201, China
2 Department of Nursing, Community Healthcare Center of Shushan Street, Hangzhou, 311201, China

* Corresponding Author: XIAOYING ZHANG. Email: email

(This article belongs to this Special Issue: Natural Products for Chronic Inflammatory Diseases: Pharmacology and Toxicology)

BIOCELL 2023, 47(6), 1307-1316. https://doi.org/10.32604/biocell.2023.028714

Abstract

Scutellarin (SCU) is a herbal flavonoid glucuronide with multiple pharmacological activities, including anti-oxidant, anti-inflammation, vascular relaxation, anti-platelet, and myocardial protection. However, the effect of SCU on complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) had not been studied. In this study, we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma levels of immunoglobulin (Ig)G, IgE, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG). Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints. The proportions of T helper type 1 (Th1) and T helper type 2 (Th2) cells of CD4+ T lymphocyte subsets were analyzed by flow cytometry. The expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) was analyzed using real-time quantitative PCR (RT-qPCR) and western blotting assays. The present study demonstrated that SCU prevented CFA-induced RA, and inhibited the expression of inflammation factors, IgG, IgE, TNF-α, IL-1β, and IL-6. While SCU also reduced the RANKL level, it increased OPG expression in RA mice. The Th1/Th2 ratio was significantly lower in mice treated with SCU. Additionally, HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment. Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.

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LI, J., WANG, Q., ZHANG, X. (2023). Scutellarin alleviates complete freund’s adjuvant-induced rheumatoid arthritis in mice by regulating the Keap1/Nrf2/HO-1 pathway. BIOCELL, 47(6), 1307–1316.



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