Anti-inflammatory and immunomodulatory effects of iridoid glycosides from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on uric acid nephropathy rats

Aims: Uric acid nephropathy (UAN) is due to excessive uric acid, which leads to hyperuricemia and kidney damage via the deposition of urate microcrystals in the kidneys. Iridoid glycosides of Paederia scandens (IGPS) is a major active component isolated from the traditional Chinese herb P. scandens (LOUR.) MERRILL (Rubiaceae). This study aimed to evaluate the anti-inflammatory and immunomodulatory effects of IGPS and its mechanism on UAN rats. Main methods: The experimental model of UAN rats was induced by using uricopoiesis promoter adenine and uricase inhibitor potassium oxonate (PO). Treatment groups received three different doses of IGPS, allopurinol (AP) and benzbromarone (BEN) daily for 24 days respectively. The histopathology of renal tissues in VAN rats were assessed for conventional morphological evaluation. The nuclear factor-kappa Bp65 (NF-kappa Bp65), monocyte chemoattractant protein-1 (MCP-1) and alpha-smooth muscle actin (alpha-SMA) protein expression of renal tissues in UAN rats were investigated by immunohistochemistry. MCP-1 and alpha-SMA mRNA levels were monitored by method of reverse transcription polymerase chain reaction (RT-PCR). Key findings: Treatment with IGPS significantly ameliorated VAN induced renal tissue injury, inhibited the biological activity of NF-kappa Bp65, MCP-1 and alpha-SMA, and suppressed the mRNA expressions of MCP-1 and alpha-SMA. Significance: IGPS exerts a protective effect against renal injury in UAN rats, possesses anti-inflammatory and immunomodulatory effects by inactivating NF-kappa Bp65 pathway transmembrane signal transduction, down regulating the expression of MCP-1 and alpha-SMA to modulate pro-inflammatory mediator production in nephropathy tissue to improve renal fibrosis in UAN rats. (c) 2012 Elsevier Inc. All rights reserved.