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.
Fifteen new and rare iridoid glucoside dimers, cornusides A-O (1-15), and 10 known iridoid glucosides (16-25) were isolated from the fruit of Cornus officinalis. These new chemical structures were established through spectroscopic analysis (UV, IR, HRESIMS, 1D and 2D NMR). Compounds 1-25 were tested for their inhibitory activities by measuring IL-6-induced STAT3 promoter activity in HepG2 cells, and 3, 12, 17, 22, and 23 showed inhibitory effects, with IC values of 11.9, 12.2, 14.0, 7.0, and 6.9 μM, respectively.
Fischernolides A–D (1–4), representing the rare 28-carbon meroterpenoid skeleton of abietane and an acylphloroglucinol conjugate, bearing an α-furanone or α-pyrone ring, were isolated and identified from the roots of Euphorbia fischeriana.
Five new ent-abietane diterpenoid fischeriabietanes A–E (1–5), along with nine known analogues (6–14), were isolated from the roots of Euphorbia fischeriana and their biosynthetic relationships were discussed.
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