Inflammation,
fibrosis, and
lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in
diabetes mellitus type 2.
Berberine (BBR) has been reported to have beneficial effects on
diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2
diabetic nephropathy rat model induced by a high-fat diet and low-dose
streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24-h
albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of
blood glucose and
lipids, inhibited urinary excretion of
albumin, and attenuated renal histological
injuries in diabetic rats.
Berberine treatment also inhibited renal
inflammation, which was associated with inactivation of nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a result, the upregulation of pro-inflammatory
cytokines (
interleukin-1β, tumour
necrosis factor-α) and
chemokine (
monocyte chemotactic protein-1) was blocked. In addition, BBR treatment also inactivated
transforming growth factor-β/Smad3 signalling and suppressed renal
fibrosis, including expression of
fibronectin,
collagen I, and
collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2
diabetic nephropathy by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal
inflammation and
transforming growth factor-β/Smad3 signalling pathway.