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


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 24days respectively. The histopathology of renal tissues in UAN rats were assessed for conventional morphological evaluation. The nuclear factor-κBp65 (NF-κBp65), monocyte chemoattractant protein-1 (MCP-1) and α-smooth muscle actin (α-SMA) protein expression of renal tissues in UAN rats were investigated by immunohistochemistry. MCP-1 and α-SMA mRNA levels were monitored by method of reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
Treatment with IGPS significantly ameliorated UAN induced renal tissue injury, inhibited the biological activity of NF-κBp65, MCP-1 and α-SMA, and suppressed the mRNA expressions of MCP-1 and α-SMA.


CONCLUSIONS
IGPS exerts a protective effect against renal injury in UAN rats, possesses anti-inflammatory and immunomodulatory effects by inactivating NF-κBp65 pathway transmembrane signal transduction, down regulating the expression of MCP-1 and α-SMA to modulate pro-inflammatory mediator production in nephropathy tissue to improve renal fibrosis in UAN rats.
Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.
Wenjing
W
Zhu
Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.
Mingqun
M
Pang
Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.
Liuyi
L
Dong
Department of Anatomy, Anhui Medical University, Hefei, Anhui, China.
Xueying
X
Huang
Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China.
Shuangmiao
S
Wang
Department of Pharmacology, Anhui Medical University, Hefei, Anhui, China. Electronic address: lanlzhou@yahoo.com.cn.
Lanlan
L
Zhou
D000199:Actins / Q000032:analysis; D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001553:Benzbromarone / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000032:analysis; D000081004:Cyclopentane Monoterpenes; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005960:Glucosides / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D057889:Iridoid Glycosides / Q000627:therapeutic use*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008516:Medicine, Chinese Traditional; D011714:Pyrans / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019666:Rubiaceae; D051996:Transcription Factor RelA / Q000032:analysis; D014527:Uric Acid / Q000097:blood*
D000199:Actins; D000493:Allopurinol; D000893:Anti-Inflammatory Agents; D001553:Benzbromarone; D018932:Chemokine CCL2; D000081004:Cyclopentane Monoterpenes; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D007155:Immunologic Factors; D057889:Iridoid Glycosides; D011714:Pyrans; D051996:Transcription Factor RelA; D014527:Uric Acid; C491766:Ccl2 protein, rat; C498862:Acta2 protein, rat; C077956:asperuloside