Effect of Dihydroartemisinin on the Activity of Cardiac Fibroblasts and p38MAPK/NF-κB Pathway Activation

GUO Ming; SHAN Tieqiang; LI Junjiao; CAI Ansheng; MA Lina; LI Bei; LIU Ningna

doi:10.12102/j.issn.1672-1349.2025.11.009

Abstract：Objective:To observe the effects of Dihydroartemisinin(DHA)on the activity of cardiac fibroblasts(CFs)stimulated by lipopolysaccharide in vitro and the expression of p38 mitogen-activated protein kinase(p38MAPK)/nuclear factor κB(NF-κB)pathway proteins in the cells.To explore the anti-inflammatory mechanism of DHA on myocardial fibrosis.Methods:The tissues from the ventricles of lactating mice were cut and digested by enzymes to obtain CFs.The cells were divided into the normal group,DHA group,the lipopolysaccharide group,and the DHA intervention group.The normal group was cultured in conventional culture medium,the DHA group was cultured in conventional culture medium with 100 μg/mL DHA,the lipopolysaccharide group was cultured in conventional culture medium with 50 μg/mL lipopolysaccharide,and the DHA intervention group was cultured in conventional culture medium with 100 μg/mL DHA and 50 μg/mL lipopolysaccharide.After 48 hours of cell treatment,the absorbance values of cell proliferation in each group were detected.The levels of type Ⅰ collagen,type Ⅲ collagen,fibronectin and inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1 β(IL-1β)were tested in the quantitative culture medium of the detection box.Western Blot was used to detect the levels of p38MAPK/NF-κB pathway proteins p38MAPK,phosphorylated p38MAPK(p-p38MAPK),NF-κBp65 and phosphorylated NF-κBp65(p-NF-κBp65).Results:Compared with the normal group,there were no statistically significant differences in the absorbance values of cell proliferation,the levels of type Ⅰ collagen,type Ⅲ collagen,fibronectin in the culture medium,the levels of inflammatory factors TNF-α,IL-6,and IL-1β,and the protein levels of the p38MAPK/NF-κB pathway in the DHA group(P＞0.05).The absorbance value of cell proliferation,the levels of type Ⅰ collagen,type Ⅲ collagen,fibronectin and inflammatory factors TNF-α,IL-6,IL-1β in the culture medium,the levels of p38MAPK/NF-κB pathway proteins p38MAPK,p-P38MAPK,NF-κBp65 and p-NF-κBp65 in the lipopolysaccharide group significantly increased compared with that in the normal group(P＜0.01).The absorbance value of cell proliferation,the levels of type Ⅰ collagen,type Ⅲ collagen,fibronectin and inflammatory factors TNF-α,IL-6,IL-1β in the culture medium,the levels of p38MAPK/NF-κB pathway proteins p38MAPK,p-p38MAPK,NF-κBp65 and p-NF-κBp65 in the DHA intervention group were significantly lower than those in the lipopolysaccharide group(P＜0.01).Conclusion:DHA can reduce the proliferation of myocardial fibroblasts stimulated by lipopolysaccharide and the activity of secreting collagen and inflammatory factors,which is closely related to its antagonistic activity against the p38MAPK/NF-κB signaling pathway.