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. 2021 Dec 15:2021:1829736.
doi: 10.1155/2021/1829736. eCollection 2021.

Dihydroartemisinin Promoted Bone Marrow Mesenchymal Stem Cell Homing and Suppressed Inflammation and Oxidative Stress against Prostate Injury in Chronic Bacterial Prostatitis Mice Model

Shen Li  1 , Yongzhang Li  2 , Xiaozhe Su  1 , Aiyun Han  1 , Yang Cui  1 , Shuyue Lv  1 , Jin Zhang  1 , Chao Li  1
Affiliations

Dihydroartemisinin Promoted Bone Marrow Mesenchymal Stem Cell Homing and Suppressed Inflammation and Oxidative Stress against Prostate Injury in Chronic Bacterial Prostatitis Mice Model

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

Abstract

Although bone marrow mesenchymal stem cells (BMMSCs) are effective in treating chronic bacterial prostatitis (CBP), the homing of BMMSCs seems to require ultrasound induction. Dihydroartemisinin (DHA) is an important derivative of artemisinin (ART) and has been previously reported to alleviate inflammation and autoimmune diseases. But the effect of DHA on chronic prostatitis (CP) is still unclear. This study aims to clarify the efficacy and mechanism of DHA in the treatment of CBP and its effect on the accumulation of BMMSCs. The experimental CBP was produced in C57BL/6 male mice via intraurethrally administered E. coli solution. Results showed that DHA treatment concentration-dependently promoted the accumulation of BMMSCs in prostate tissue of CBP mice. In addition, DHA and BMMSCs cotreatment significantly alleviated inflammation and improved prostate damage by decreasing the expression of proinflammatory factors such as TNF-α, IL-1β, and chemokines CXCL2, CXCL9, CXCL10, and CXCL11 in prostate tissue of CBP mice. Moreover, DHA and BMMSCs cotreatment displayed antioxidation property by increasing the production of glutathione peroxidase (GSH-Px), SOD, and decreasing malondialdehyde (MDA) expression. Mechanically, DHA and BMMSCs cotreatment significantly inhibited the expression of TGFβ-RI, TGFβ-RII, phosphor (p)-Smad2/3, and Smad4 in a dose-dependent manner while stimulated Smad7 expression in the same manner. In conclusion, our findings provided evidence that DHA effectively eliminated inflammatory and oxidative stress against prostate injury, and this effect involved the TGF-β/Smad signaling pathway in CBP.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Observation of GFP-LUC adenovirus-transfected BMSC viability. (a) Green fluorescent levels in BMMSCs at 24 h 48 h and 72 h after transfection with GFP-LUC adenovirus (×100 magnification). The scale bar indicates 200 μm. (b) Cell viability was tested using the CCK-8 assay. For B mean ± standard errors of means are reported.
Figure 2
Figure 2
DHA promoted homing of BMMSCs to prostate tissue. (a) Fluorescence images showing GFP + cells in prostate tissue (×200 magnification). (b) Average fluorescence intensity of GFP. (c-e) Fluorescence images and average fluorescence intensity of CD45, CD29, and CD44 levels in prostate tissue (×200 magnification). The scale bar indicates 20 μm. ∗∗denotes P < 0.01 vs con group and ##denotes P < 0.01 vs BMMSCs group. For B, D, and E, mean ± standard errors of means are reported.
Figure 3
Figure 3
Effect of DHA and BMMSC cotreatment on histopathological features and inflammatory mediators in CBP mice. (a) H&E stain of prostate tissue from C57BL/6 mice in the different groups. The scale bar indicates 50 μm (×200 magnification) and 20 μm (×400 magnification). (b–f) Quantifications of TNF-α, IL-1β, CXCL2, CXCL9, CXCL10, and CXCL11 levels in prostate tissue of all groups were examined using an ELISA assay. ∗∗denotes P < 0.01 vs con group, # denotes P < 0.05 vs BMMSCs group, and ## denotes P < 0.01 vs BMMSCs group. For (b)–(f), mean ± standard errors of means are reported.
Figure 4
Figure 4
DHA and BMMSC cotreatment attenuated the oxidative stress in CBP mice. Expression of oxidative stress-related factors MDA (a), SOD (b), and GSH-Px (c) in the prostatic tissues of mice was detected by ELISA. ∗∗denotes P < 0.01 vs con group, # denotes P < 0.05 vs BMMSCs group, and ## denotes P < 0.01 vs BMMSCs group. For all the graphs, mean ± standard errors of means are reported.
Figure 5
Figure 5
DHA inhibited TGF-β/Smad signaling pathway in CBP mice. (a) Representative bands of Western blot analysis. Expression of TGFβ-RI (b), TGFβ-RII (c), p-Smad2/3 (d), Smad4 (e), and Smad7 (f) in the prostatic tissues of mice was detected by Western blot. ∗∗denotes P < 0.01 vs con group, # denotes P < 0.05 vs BMMSCs group, and ## denotes P < 0.01 vs BMMSCs group. For (b)–(f), mean ± standard errors of means are reported.
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