Expation of the therapeutic effect and mechanism of Nepetoidin B on collagen-induced arthritis in mice
10.3760/cma.j.cn141217-20240416-00130
- VernacularTitle:Nepetoidin B对小鼠胶原诱导关节炎疗效及作用机制探讨
- Author:
Yaozong SUN
1
;
Tao HE
;
Zhuo LIU
;
Fang SHUI
;
Ruixue TIAN
;
Baoqing TANG
;
Jianhui ZHANG
Author Information
1. 山西医科大学第二医院骨科，太原 030001
- Publication Type:Journal Article
- Keywords:
Arthritis, rheumatoid;
Oxidative stress;
Nepetoidin B;
Nrf2/HO1 pathway
- From:
Chinese Journal of Rheumatology
2025;29(3):213-218
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the therapeutic effect and potential mechanism of Nepetoidin B on rheumatoid arthritis (RA).Methods:DBA/1 mice were divided into four groups using the random number method, namely the control group, model group, methotrexate group, and Nepetoidin B group. The collagen-induced arthritis (CIA) model was prepared. Mice were treated from day 21th to day 60th. Arthritis symptoms were evaluated every three days during treatment. At the end of treatment, pathological changes of joint tissue were observed through HE staining. Serum IL-17, IL-6, MDA, and NO levels were measured using ELISA and biochemical colorimetric assays. The Nrf2/HO1 pathway in joint tissues was detected using western blot. A group of CIA mice was treated with Nepetoidin B, followed by an Nrf2 inhibitor to validate the mechanism. One-way analysis of variance was used to compare between multiple groups with homogeneity of variance, pairwise comparison using LSD- t test. Results:The study found that mice treated with methotrexate and Nepetoidin B exhibited a significant reduction in arthritis scores(CIA+Meth group 5.2±1.3, CIA+NepB group 6.8±1.2 vs. CIA group 11.0±1.7, t=6.69, P=0.004; t=5.00, P=0.009), and joint histopathology compared to the CIA mice(CIA+Meth group 1.5±1.0, CIA+NepB group 2.2±0.8 vs. CIA group 4.0±0.9, t=4.44, P<0.001; t=3.84, P=0.005). Additionally, there was a significant decrease in serum IL-17[CIA+Meth group(257±69)ng/ml, CIA+NepB group (279±103)ng/ml vs. CIA group(414±71)ng/ml, t=3.86, P=0.006; t=2.63, P=0.020], IL-6[CIA+Meth group(32±6)ng/ml, CIA+NepB group (44±5)ng/ml vs. CIA group(56±11)ng/ml, t=4.69, P<0.001; t=2.48, P=0.040) ,MDA [CIA+Meth group(22±4)μmol/L, CIA+NepB group(22±8)μmol/L vs. CIA group(34±11)μmol/L, t=2.77, P=0.038; t=2.29, P=0.049]and NO[ CIA+Meth group(37±12)μmol/L, CIA+NepB group(37±11)μmol/L vs. CIA group(56±12)μmol/L, t=2.71, P=0.040; t=2.90, P=0.035] levels, and a significant elevation in the Nrf2( 0.263±0.021, 0.273±0.022 vs. 0.221±0.034, t=3.18, P=0.044; t=2.70, P=0.049)/HO1 (0.524±0.021, 0.501±0.014 vs. 0.453±0.033, t=3.95, P=0.006; t=3.41, P=0.032) pathway in methotrexate and Nepetoidin B treated group. It was also observed that Nrf2 inhibitors could counteract the treatment effects of Nepetoidin B on arthritis (1.8±0.8 vs. 3.2±0.8, t=3.07, P=0.024). Conclusion:Nepetoidin B has the ability to inhibit oxidative stress by activating the Nrf2/HO1 pathway, which alleviates collagen-induced arthritis in mice.
