title: Anti-inflammatory activity of curcumin-loaded solid lipid nanoparticles in IL-1β transgenic mice subjected to the lipopolysaccharide-induced sepsis.
abstract: Sepsis is a significant public healthcare problem, affecting millions of people worldwide each year, killing one in four, and increasing in incidence. Thus, advanced therapeutic strategies are required to treat sepsis patients. Curcumin (Cur) is a promising anti-inflammatory agent for various inflammatory disorders. However, the therapeutic efficacy of Cur is limited due to poor aqueous solubility, rapid degradation, and low bioavailability. The aims of this study were to evaluate the therapeutic potential of Cur-loaded solid lipid nanoparticles (Cur-SLNs) for sepsis treatment. A firefly luciferase transgenic mouse was used to monitor real time interleukin 1β (IL-1β) expression in lipopolysaccharide (LPS)-induced sepsis model to examine the protective effect of Cur-SLNs, and to elucidate its underlying molecular mechanisms. Mice (female or male) were intraperitoneally administered with free Cur or Cur-SLNs (30 mg/kg) before the intraperitoneal delivery of LPS (3 mg/kg). Our results indicated that Cur-SLNs can effectively reduced levels of IL-1β expression compared to free Cur, especially at 3 h after LPS injection. Also, Cur-SLNs significantly decreased the expression of serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β as compared with free Cur, but augmented anti-inflammatory cytokine IL-10 by ELISA assay. Further, marked alleviation of the sepsis-induced damage to organs, including kidney, liver, and heart was observed with Cur-SLNs treatment as determined by hematoxylin/eosin-staining. Western blot analyses revealed that Cur-SLNs can significantly lower the expression levels of TLR4, TLR2, and TNF-α in lymph node tissues. Meanwhile, it showed suppressions of NF-κB activation and IκBα degradation levels. In conclusion, we suggested that Cur-SLNs may be used as an effective and safe therapeutic agent in treating sepsis in high-risk patient groups.
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China; Research Centre for Model Organisms, Shanghai, PR China.
authors.forename: Haoyue
authors.initials: H
authors.lastname: Wang
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China; Research Centre for Model Organisms, Shanghai, PR China. Electronic address: jfei@tongji.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.affiliation: Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China. Electronic address: wsl@tongji.edu.cn.
authors.forename: Shilong
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003474:Curcumin / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004337:Drug Carriers; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics*; D008055:Lipids / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles; D011401:Promoter Regions, Genetic; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy*; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004337:Drug Carriers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008055:Lipids; D008070:Lipopolysaccharides; D003474:Curcumin
keywords: Curcumin; IL-1β; Lipopolysaccharide; Sepsis; Solid lipid nanoparticles; TLR4