1. Ethyl Acetate Fractions of Salvia miltiorrhiza Bunge (Danshen) Crude Extract Modulate Fibrotic Signals to Ameliorate Diabetic Kidney Injury.
- Author
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Hsu YC, Shih YH, Ho C, Liu CC, Liaw CC, Lin HY, and Lin CL
- Subjects
- Animals, Mice, Male, Transforming Growth Factor beta1 metabolism, Mesangial Cells drug effects, Mesangial Cells metabolism, Fibronectins metabolism, Mice, Inbred C57BL, PPAR alpha metabolism, Plant Extracts pharmacology, Plant Extracts chemistry, Glucose metabolism, Salvia miltiorrhiza chemistry, Diabetic Nephropathies drug therapy, Diabetic Nephropathies metabolism, Diabetic Nephropathies pathology, Drugs, Chinese Herbal pharmacology, Drugs, Chinese Herbal therapeutic use, Drugs, Chinese Herbal chemistry, PPAR gamma metabolism, Fibrosis, Acetates chemistry, Acetates pharmacology, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Experimental metabolism
- Abstract
Diabetic nephropathy, a leading cause of end-stage renal disease, accounts for significant morbidity and mortality. It is characterized by microinflammation in the glomeruli and myofibroblast activation in the tubulointerstitium. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is shown to possess anti-inflammatory and anti-fibrotic properties, implying its renal-protective potential. This study investigates which type of component can reduce the damage caused by diabetic nephropathy in a single setting. The ethyl acetate (EtOAc) layer was demonstrated to provoke peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ activities in renal mesangial cells by dual luciferase reporter assay. In a high glucose (HG)-cultured mesangial cell model, the EtOAc layer substantially inhibited HG-induced elevations of interleukin-1β, transforming growth factor-β1 (TGF-β1), and fibronectin, whereas down-regulated PPAR-γ was restored. In addition, among the extracts of S. miltiorrhiza , the EtOAc layer effectively mitigated TGF-β1-stimulated myofibroblast activation. The EtOAc layer also showed a potent ability to attenuate renal hypertrophy, proteinuria, and fibrotic severity by repressing diabetes-induced proinflammatory factor, extracellular matrix accumulation, and PPAR-γ reduction in the STZ-induced diabetes mouse model. Our findings, both in vitro and in vivo, indicate the potential of the EtOAc layer from S. miltiorrhiza for future drug development targeting diabetic nephropathy.
- Published
- 2024
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