The antifibrotic and anti-inflammatory effects of icariin on the kidney in a unilateral ureteral obstruction mouse model

Hsin-An Chen; Chang-Mu Chen; Siao-Syun Guan; Chih-Kang Chiang; Cheng-Tien Wu; Shing-Hwa Liu

doi:10.1016/j.phymed.2019.152917

The antifibrotic and anti-inflammatory effects of icariin on the kidney in a unilateral ureteral obstruction mouse model

Phytomedicine. 2019 Jun:59:152917. doi: 10.1016/j.phymed.2019.152917. Epub 2019 Apr 3.

Authors

Hsin-An Chen¹, Chang-Mu Chen², Siao-Syun Guan³, Chih-Kang Chiang⁴, Cheng-Tien Wu⁵, Shing-Hwa Liu⁶

Affiliations

¹ Graduate Institute of Clinical Medicine and Department of Surgery, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
² Department of Surgery, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
³ Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan.
⁴ Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Integrated Diagnostics & Therapeutics, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
⁵ Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Electronic address: d94447001@ntu.edu.tw.
⁶ Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Paediatrics, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: shinghwaliu@ntu.edu.tw.

PMID: 30978648
DOI: 10.1016/j.phymed.2019.152917

Abstract

Background: The pathology change of renal tubulointerstitial fibrosis is a critical feature of chronic kidney disease (CKD), regardless of the primary insults. The infiltration of inflammatory cells and the consecutive secretion of profibrotic factors are frequently and conspicuously observed during the development of renal fibrosis. Icariin, an active polyphenol of the Epimedium genus, has been found to alleviate the symptoms of chronic diseases like diabetes, neurodegeneration, and heart and renal diseases. The effect and mechanism of icariin on the prevention of CKD-associated renal fibrosis still needed clarification.

Purpose: The aims of this study were to investigate whether icariin treatment improves the development of CKD-associated renal fibrosis and its possible mechanism.

Methods: An experimental unilateral ureteral obstruction (UUO)-induced chronic renal fibrosis mouse model was used. Mice were orally administered with icariin (20 mg/kg/day) for 3 consecutive days before and 14 consecutive days after UUO surgery.

Results: The pathological changes, collagen deposition, and protein expressions of profibrotic factors (transforming growth factor-β and connective tissue growth factor) and fibrotic markers (α-smooth muscle actin and fibronectin), which were significantly elevated in the kidneys of UUO mice, could be significantly reversed by icariin treatment. Icariin treatment also significantly inhibited the increased Smad2/3 and decreased E-cadherin protein expressions in the kidneys of UUO mice. Icariin treatment prominently mitigated the protein expression of proinflammatory factors like nuclear factor-κB, cyclooxygenase-2, interleukin 1-β and prooxidative enzyme (NADPH oxidase-4), and it increased the protein expression of antioxidative enzymes (superoxide dismutase and catalase).

Conclusion: Icariin treatment protects against CKD-associated renal fibrosis via its antifibrotic and anti-inflammatory properties. Icariin may serve as a therapeutic agent in the prevention of CKD-associated renal fibrosis.

Keywords: Chronic kidney disease; Icariin; Renal fibrosis; Transforming growth factor-β; Unilateral ureteral obstruction.

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology
Collagen / metabolism
Disease Models, Animal
Fibronectins / metabolism
Fibrosis / etiology
Fibrosis / prevention & control
Flavonoids / therapeutic use*
Kidney / drug effects*
Kidney Diseases / drug therapy*
Male
Mice
Transforming Growth Factor beta / metabolism
Ureteral Obstruction / complications
Ureteral Obstruction / etiology*

Substances

Anti-Inflammatory Agents
Fibronectins
Flavonoids
Transforming Growth Factor beta
Collagen
icariin