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Mechanistic study of Danggui Shaoyao San amelioration of renal fibrosis in db/db mice through the Wnt/β-catenin pathway
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DOI   10.11656/j.issn.1672-1519.2026.09.14
Key Words   Danggui Shaoyao San;diabetic kidney disease;renal interstitial fibrosis;db/db mice;Wnt/β-catenin
Author NameAffiliationE-mail
WANG Zixuan Graduate School of Hebei University of Chinese Medicine, Shijiazhuang 050000, China  
LI Ruijia Graduate School of Hebei University of Chinese Medicine, Shijiazhuang 050000, China  
GUO Shilong Graduate School of Hebei University of Chinese Medicine, Shijiazhuang 050000, China  
HOU Luyu Graduate School of Hebei University of Chinese Medicine, Shijiazhuang 050000, China  
SHI Wenjing Graduate School of Hebei University of Chinese Medicine, Shijiazhuang 050000, China  
QIANG Yitong The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang 050011, China  
GUO Dengzhou The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang 050011, China guodengzhou@sohu.com 
Abstract
    [Objective] To investigate whether Danggui Shaoyao San(DSS)improves renal fibrosis by regulating the Wnt/β-catenin pathway,thereby delaying the progression of diabetic kidney disease(DKD). [Methods] Eight SPF-grade male db/m mice served as the normal control group. Forty SPF-grade male db/db mice were randomly divided into five groups(n=8 each):model group,irbesartan group [0.025 g/ (kg·d)],low-dose Danggui Shaoyao San group [16.77 g/ (kg·d)],medium-dose Danggui Shaoyao San group [33.54 g/ (kg·d)], and high-dose Danggui Shaoyao San group [67.08 g/ (kg·d)]. The normal and model groups received equal volumes of saline via gastric gavage,with all groups receiving continuous gavage for 8 weeks. During the study period,fasting blood glucose levels were monitored and body weights were recorded. After 8 weeks of continuous administration,serum creatinine(Scr),blood urea nitrogen(BUN),and urinary microalbumin(mALB)levels were measured. Renal pathological changes and fibrosis severity were assessed using hematoxylin and eosin(HE),Masson’s trichrome,and periodic acid-Schiff(PAS)staining. Western blot and immunohistochemistry(IHC)were used to detect the expression and localization of Collagen I,E-Cadherin,α-SMA,Wnt4,and β-catenin proteins in renal tissues;real- time quantitative polymerase chain reaction(RT-qPCR)was employed to measure mRNA levels of Collagen I,E-Cadherin,and α-SMA in renal tissues. [Results] Compared with the normal group,the model group exhibited increased blood glucose,body weight,serum creatinine,blood urea nitrogen,and urinary microalbumin levels. The mesangial matrix in the glomeruli was significantly increased, tubules showed vacuolar degeneration and disorganized arrangement,and the renal interstitium demonstrated inflammatory cell infiltration with prominent collagen fiber striations. Expression of Collagen I,α-SMA,Wnt4,β-catenin increased,while E-cadherin expression decreased in renal tissue(P<0.01 or P<0.05). Compared with the model group,all treatment groups showed improved conditions with varying degrees of reduction in blood glucose,body weight,serum creatinine,blood urea nitrogen,and urinary microalbumin. Renal tissue damage and fibrosis improved to varying extents,and renal tissue expression of collagen I,α-SMA,Wnt4,β-catenin decreased,while E-Cadherin expression increased(P<0.01 or P<0.05). [Conclusion] Danggui Shaoyao San effectively ameliorates renal interstitial fibrosis by improving EMT and reducing extracellular matrix accumulation,potentially through inhibition of the Wnt/β-catenin pathway.

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