Xiexin decoction, a herbal therapeutic agent commonly used in
traditional Chinese medicine, is recognized for its beneficial effects on
diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis
alkaloids (A), Radix et Rhizoma Rhei
polysaccharides (P), and Radix Scutellaria
flavones (F). Our previous studies have shown that a combination of A, P, and F (APF) exhibits renoprotective effects against
diabetic nephropathy. This study was aimed at determining the effects of APF on renal
fibrosis in
diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively) once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal
inflammation, and
fibrosis. APF treatment significantly ameliorated
glucose and lipid metabolism dysfunction, decreased urinary
albumin excretion, normalized
creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal
inflammation mediators such as
intercellular adhesion molecule-1,
monocyte chemotactic protein-1,
tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB). APF treatment also reduced type I and IV
collagen, transforming growth factor-β1 (TGF-β1), and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal
fibrosis in
diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and
protein expression of α-smooth muscle actin,
collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high
glucose concentrations. Our findings indicate that treatment with multi-component herbal therapeutic formulations may be a useful approach for the treatment of
diabetic nephropathy.