title: Targeting inflammatory mediators with ferulic acid, a dietary polyphenol, for the suppression of monosodium urate crystal-induced inflammation in rats.
abstract: OBJECTIVE
  The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug.
  
  
  METHODS
  Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and β-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro-inflammatory cytokines (TNF-α and IL-1β), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-κB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-κB p65 and TNF-α was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-κB, apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro-caspase-1.
  
  
  RESULTS
  In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-α and IL-1β); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-κB p65. In addition, the protein expression of NF-κB p65 and TNF-α was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards pro-caspase-1, NF-κB, PYCARD/ASC, and NLRP3.
  
  
  CONCLUSIONS
  Our findings demonstrate the potential anti-inflammatory effect of ferulic acid on MSU crystal-induced inflammation in rats.
authors: Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, India.
authors: Hari Madhuri
authors: HM
authors: Doss
authors: Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, India.
authors: Chandrima
authors: C
authors: Dey
authors: Division of Bio-informatics, School of Bio Sciences and Technology, VIT University, Vellore 632014, India.
authors: C
authors: C
authors: Sudandiradoss
authors: Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, India. Electronic address: mkr474@gmail.com.
authors: Mahaboob Khan
authors: MK
authors: Rasool
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015210:Arthritis, Gouty / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D003373:Coumaric Acids / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D010944:Plants; D059808:Polyphenols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000633:toxicity*
chemical_list: D000893:Anti-Inflammatory Agents; D003373:Coumaric Acids; D018836:Inflammation Mediators; D059808:Polyphenols; D014527:Uric Acid; C004999:ferulic acid
keywords: Acute gouty arthritis; Colchicine; Ferulic acid; Inflammasome; Pro-inflammatory cytokines