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. 2022 May 4:13:871481.
doi: 10.3389/fphar.2022.871481. eCollection 2022.

Huangqi Guizhi Wuwu Decoction Improves Arthritis and Pathological Damage of Heart and Lung in TNF-Tg Mice

Yi Wang  1   2   3 , Tao Chen  1   2   4   5 , Can Yang  1   2   4 , Qiang Li  1   2   4 , Mengjiao Ma  1   2   3 , Hao Xu  1   2   4 , Qi Shi  1   2   4 , Yongjun Wang  1   2   4 , Youhua Wang  1   2   3 , Qianqian Liang  1   2   4
Affiliations

Huangqi Guizhi Wuwu Decoction Improves Arthritis and Pathological Damage of Heart and Lung in TNF-Tg Mice

Yi Wang et al. Front Pharmacol. .

Abstract

Background: Huangqi Guizhi Wuwu Decoction (HGWD) is a traditional and effective Chinese medicine compound decoction for the treatment of rheumatoid arthritis (RA). However, there is few research on the treatment of rheumatoid cardiopulmonary complications. The present study was to study whether HGWD can alleviate the pathological changes caused by rheumatoid arthritis and cardiopulmonary complications. Methods: Five 3-month-old TNF-Tg mice were treated with HGWD (9.1 g/kg) once a day or the same dose of normal saline lasted for 8 weeks, and wild-type littermates of the same age were used as a negative control, and methotrexate (MTX) was intraperitoneally administered as a positive control. After the treatment, pathological staining was performed on the mouse ankle joints, heart, and lungs. Result: It was found that HGWD reduced the inflammation of the ankle joint synovium in TNF-Tg mice, and reduced myocardial hypertrophy, inflammatory infiltration and fibrosis of heart, as well as lung inflammation and fibrosis. Immunohistochemical staining with anti-TNF-α antibody showed that HGWD reduced the expression of TNF-α in the heart of TNF-Tg mice. Conclusion: In conclusion, HGWD alleviates joint inflammation in TNF-Tg mice and reduces the pathological changes of the heart and lungs.

Keywords: Huangqi Guizhi Wuwu Decoction; TNF-Tg mice; cardiopulmonary complications of RA; rheumatoid arthritis; traditional Chinese medicine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
HGWD alleviates the infiltration of ankle joint inflammation in TNF-Tg mice. The treatment group was gavage with HGWD, MTX was administered as the positive control group and nontransgenic littermates were used as the wild-type control group. After administration, the optimal right ankle section of each mouse was used for HE staining, and a slice was selected from each mouse as sample statistics. (A) Representative HE stained sections show that the inflammation of the ankle joint of HGWD-treated mice was reduced. Bar = 200 μm, the black arrow indicates inflammatory synovial tissue. (B) Quantification of synovial area. The values are the mean plus or minus SD of each group of 5 legs. *p < 0.05, compared with WT group; # p < 0.05, compared with TNF-Tg group.
FIGURE 2
FIGURE 2
HGWD reduces the inflammatory infiltration of the heart of TNF-Tg mice. Mouse hearts were taken for HE staining analysis. (A) Representative HE stained sections show that the heart of TNF-Tg mice has obvious inflammation infiltration, and the arrangement of cardiomyocytes is disordered. The inflammatory infiltration of the heart of mice treated with HGWD was reduced. (B) Partially enlarged picture.
FIGURE 3
FIGURE 3
HGWD alleviates cardiomyocyte hypertrophy in TNF-Tg mice. (A) A representative mouse heart WGA-stained section showed that the cross-sectional area of cardiomyocytes in TNF-Tg mice increased, and the cross-sectional area after HGWD treatment was smaller than that in the TNF-Tg group. Bar = 20 μm. (B) Quantification of the cross-sectional area of cardiomyocytes. Values are the mean plus or minus SD of 5 hearts in each group. *p < 0.05, compared with WT group; # p < 0.05, compared with TNF-Tg group.
FIGURE 4
FIGURE 4
HGWD reduces myocardial fibrosis in TNF-Tg mice. (A) Representative Masson-stained sections of mouse heart showed obvious fibrosis, and the area of fibrosis decreased after HGWT treatment. Bar = 20 μm. (B) Quantification of the area of myocardial fibrosis. Values are the mean plus or minus SD of 5 hearts in each group. *p < 0.05, compared with WT group; # p < 0.05, compared with TNF-Tg group.
FIGURE 5
FIGURE 5
HGWD reduces the expression of TNF-α in myocardial tissue of TNF-Tg mice. (A) Representative mice heart immunohistochemical staining sections showed that the expression of TNF-α in TNF-Tg mice was increased, and after treatment, it was lower than that in the TNF-Tg group. Bar = 20 μm. (B) Quantification of the positive area of TNF-α. Values are the mean plus or minus SD of 5 hearts in each group. *p < 0.05, compared with WT group; # p < 0.05, compared with TNF-Tg group.
FIGURE 6
FIGURE 6
HGWD reduces lung inflammation infiltration in TNF-Tg mice. (A) TNF-Tg mice showed severe inflammatory infiltration near the lung bronchi, and the alveolar interval was significantly thickened. The HGWD-treated mice had reduced lung inflammation infiltration, and the alveolar interval was smaller than that in the TNF-Tg group. Bar = 100 μm. (B) Quantification of lung inflammation infiltration area. Values are the mean plus or minus SD of 5 lungs in each group. *p < 0.05, compared with WT group; # p < 0.05, compared with TNF-Tg group.
FIGURE 7
FIGURE 7
HGWD reduces lung fibrosis in TNF-Tg mice. (A) TNF-Tg mice have obvious fibrosis near the lung bronchus, and the fibrotic tissue is blue. The area of lung fibrosis in the mice treated with HGWD is reduced, and the lung fibrosis in the mice treated with MTX is aggravated. Bar = 200 μm or Bar = 50 μm. (B) Quantification of pulmonary peri bronchial fibrosis score. (C) Quantification of alveolar fibrosis score. Values are the mean plus or minus SD of 5 lungs in each group. *p < 0.05, compared with WT group; # p < 0.05, compared with TNF-Tg group.
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