Novel transdermal curcumin therapeutic preserves endothelial barrier function in a high-dose LPS rat model

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):33-40. doi: 10.1080/21691401.2022.2164584.

Abstract

Sepsis is a devastating complication of infection and injury that, through widespread endothelial dysfunction, can cause perfusion deficits and multi-organ failure. To address the recognised need for therapeutics targetting the endothelial barrier, a topical formulation (CUR; VASCEPTOR™; Vascarta Inc, Summit, NJ) was developed to transdermally deliver bio-active concentrations of curcumin-an anti-inflammatory and nitric oxide promoter. Male, Sprague Dawley rats were treated daily with lipopolysaccharide (LPS, 10 mg/kg, IP) to induce endotoxemia, and topical applications of Vehicle Control (LPS + VC; N = 7) or Curcumin (LPS + CUR; N = 7). A third group received neither LPS nor treatment (No-LPS; N = 8). After 72 h, animals were surgically prepared for measurements of physiology and endothelial dysfunction in the exteriorised spinotrapezius muscle through the extravasation of 67 kDa TRITC-BSA (albumin) and 500 kDa FITC-dextran (dextran). At 72 h, LPS + VC saw weight loss, and increases to pulse pressure, lactate, pCO2, CXCL5 (vs No-LPS) and IL-6 (vs 0 h; p < 0.05). LPS + CUR was similar to No-LPS, but with hypotension. Phenylephrine response was increased in LPS + CUR. Regarding endothelial function, LPS + CUR albumin and dextran extravasation were significantly reduced versus LPS + VC suggesting that Curcumin mitigated endotoxemic endothelial dysfunction. The speculated mechanisms are nitric oxide modulation of the endothelium and/or an indirect anti-inflammatory effect.

Keywords: Microcirculation; curcumin; endothelium; endotoxemia; extravasation; glycocalyx; sepsis.

MeSH terms

  • Albumins
  • Animals
  • Anti-Inflammatory Agents
  • Curcumin* / pharmacology
  • Dextrans
  • Endothelium
  • Endotoxemia* / chemically induced
  • Endotoxemia* / drug therapy
  • Lipopolysaccharides
  • Male
  • Nitric Oxide
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Albumins
  • Anti-Inflammatory Agents
  • Curcumin
  • Dextrans
  • Lipopolysaccharides
  • Nitric Oxide