Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 10:2021:2843623.
doi: 10.1155/2021/2843623. eCollection 2021.

Si Miao San Attenuates Inflammation and Oxidative Stress in Rats with CIA via the Modulation of the Nrf2/ARE/PTEN Pathway

Pan Shen  1 , Yao Huang  1 , Xin Ba  1 , Weiji Lin  1 , Kai Qin  1 , Hui Wang  1 , Maotao Du  1 , Ying Haung  1 , Yu Wang  1 , Zhe Chen  1 , Shenghao Tu  1
Affiliations

Si Miao San Attenuates Inflammation and Oxidative Stress in Rats with CIA via the Modulation of the Nrf2/ARE/PTEN Pathway

Pan Shen et al. Evid Based Complement Alternat Med. .

Abstract

Objective: Si Miao San (SMS) is a traditional Chinese formula used in China to treat rheumatic diseases. To date, its mechanism in rheumatoid arthritis (RA) treatment is uncertain. Our study aims to assess the antiarthritic effects of SMS in experimental arthritic rats.

Materials and methods: SMS (8.63, 4.31, and 2.16 g/kg/day) was orally administered after the first immunization from day 14 to day 53. The effects of SMS on rats with collagen-induced arthritis (CIA) were evaluated by arthritis score and histological assessment. The levels of cytokines and anti-CII antibodies in rat serum were measured by ELISAs. The expression of oxidative stress parameters was detected by biochemical assay kits. The levels of Nrf2, HO-1, NQO1, and PTEN were determined by western blotting.

Results: Medium- and high-dose SMS treatment significantly decreased arthritis scores and alleviated ankle joint histopathology in the rats with CIA. It inhibited the production of IL-6, TNF-α, COX-2, and PGE2 in rat serum. SMS also suppressed the expression of anti-CII antibodies IgG1 and IgG2a. Moreover, SMS significantly suppressed the levels of MDA and MPO in the synovial tissues while increasing the levels of SOD and CAT in the rats with CIA. The levels of Nrf2, HO-1, NQO1, and PTEN were upregulated by SMS in rat synovial tissues.

Conclusions: This study demonstrated that SMS effectively alleviated the disease progression of CIA by decreasing the levels of proinflammatory cytokines and reducing oxidative stress damage, as indicated by IL-6, TNF-α, COX-2, and PGE2 levels; inhibiting the overproduction of MDA and MPO; and enhancing antioxidant enzymes by upregulating the Nrf2/ARE/PTEN signalling pathway.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
SMS attenuated the severity of disease in the rats with CIA. (a) Paw swelling in rats. (b) Arthritis score of each group. (c) The weights of each group. The data are expressed as the means ± SEM (n = 6 rats). #P < 0.05, ##P < 0.01 vs. the control group; ∗P < 0.05, ∗∗P < 0.01 vs. the CIA group.
Figure 2
Figure 2
SMS attenuated joint injury in the rats with CIA. (a) Histological analysis of the ankle joint of each group. Original magnification 200×. (b) The histology scores for cellular proliferation, pannus formation, and joint damage were blindly evaluated. The data are expressed as the means ± SEM (n = 6 rats). #P < 0.05, ##P < 0.01 vs. the control group; ∗P < 0.05, ∗∗P < 0.01 vs. the CIA group.
Figure 3
Figure 3
SMS reduced the expression of (a) IL-6, (b) TNF-α, (c) COX-2, (d) PGE2, and anti-CII antibodies IgG1 (e) and IgG2a (f), in the serum of CIA rats. All samples were detected by ELISA in duplicate. The data are expressed as the mean ± SEM (n = 6 rats). #P < 0.05, ##P < 0.01 vs. the control group; ∗P < 0.05, ∗∗P < 0.01 vs. the CIA group.
Figure 4
Figure 4
SMS alleviated the expression of (a) SOD, (b) MPO, (c) CAT, and (d) MDA in the synovial tissues of the rats with CIA. The data are expressed as the mean ± SEM (n = 6 rats). #P < 0.05, ##P < 0.01 vs. the control group; ∗P < 0.05, ∗∗P < 0.01 vs. the CIA group.
Figure 5
Figure 5
SMS regulated the levels of Nrf2, HO-1, NQO1, and PTEN in the rats with CIA. (a) Representative bands in the western blot for each group. (b) Semiquantitative assessment of the bands in each group. The data are expressed as the mean ± SEM (n = 6 rats). #P < 0.05, ##P < 0.01 vs. the control group; ∗P < 0.05, ∗∗P < 0.01 vs. the CIA group.
See this image and copyright information in PMC

References

    1. Burmester G. R., Pope J. E. Novel treatment strategies in rheumatoid arthritis. The Lancet. 2017;389(10086):2338–2348. doi: 10.1016/s0140-6736(17)31491-5. - DOI - PubMed
    1. McInnes I. B., Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. The Lancet. 2017;389(10086):2328–2337. doi: 10.1016/s0140-6736(17)31472-1. - DOI - PubMed
    1. Chen Z., Bozec A., Ramming A., Schett G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nature Reviews Rheumatology. 2019;15(1):9–17. doi: 10.1038/s41584-018-0109-2. - DOI - PubMed
    1. Rodríguez-Ubreva J., De La Calle-Fabregat C., Li T., et al. Inflammatory cytokines shape a changing DNA methylome in monocytes mirroring disease activity in rheumatoid arthritis. Annals of the Rheumatic Diseases. 2019;78(11):1505–1516. doi: 10.1136/annrheumdis-2019-215355. - DOI - PubMed
    1. Mateen S., Rehman M. T., Shahzad S., et al. Anti-oxidant and anti-inflammatory effects of cinnamaldehyde and eugenol on mononuclear cells of rheumatoid arthritis patients. European Journal of Pharmacology. 2019;852:14–24. doi: 10.1016/j.ejphar.2019.02.031. - DOI - PubMed

LinkOut - more resources