論文 - 詳細
| RRC ID | 67819 |
|---|---|
| 著者 | Mu Y, Li J, Kang JH, Eto H, Zai K, Kishimura A, Hyodo F, Mori T, Katayama Y. |
| タイトル | A Lipid-Based Nanocarrier Containing Active Vitamin D3 Ameliorates NASH in Mice via Direct and Intestine-Mediated Effects on Liver Inflammation. |
| ジャーナル | Biol Pharm Bull |
| Abstract |
The gut-liver axis may be involved in non-alcoholic steatohepatitis (NASH) progression. Pathogen-associated molecular patterns leak through the intestinal barrier to the liver via the portal vein to contribute to NASH development. Active vitamin D3 (1,25(OH)2D3) is a potential therapeutic agent to enhance the intestinal barrier. Active vitamin D3 also suppresses inflammation and fibrosis in the liver. However, the adverse effects of active vitamin D3 such as hypercalcemia limit its clinical use. We created a nano-structured lipid carrier (NLC) containing active vitamin D3 to deliver active vitamin D3 to the intestine and liver to elicit NASH treatment. We found a suppressive effect of the NLC on the lipopolysaccharide-induced increase in permeability of an epithelial layer in vitro. Using mice in which NASH was induced by a methionine and choline-deficient diet, we discovered that oral application of the NLC ameliorated the permeability increase in the intestinal barrier and attenuated steatosis, inflammation and fibrosis in liver at a safe dose of active vitamin D3 at which the free form of active vitamin D3 did not show a therapeutic effect. These data suggest that the NLC is a novel therapeutic agent for NASH. |
| 巻・号 | 43(9) |
| ページ | 1413-1420 |
| 公開日 | 2020-1-1 |
| DOI | 10.1248/bpb.b20-00432 |
| PMID | 32879216 |
| MeSH | Administration, Oral Animals Caco-2 Cells Calcitriol / administration & dosage* Calcitriol / adverse effects Cell Culture Techniques Coculture Techniques Disease Models, Animal Drug Carriers / chemistry* Gastrointestinal Microbiome / immunology Hepatitis / drug therapy* Hepatitis / immunology Hepatitis / pathology Humans Hypercalcemia / chemically induced Hypercalcemia / prevention & control Intestinal Mucosa / drug effects* Intestinal Mucosa / immunology Intestinal Mucosa / microbiology Intestinal Mucosa / pathology Lipids / chemistry Lipopolysaccharides / administration & dosage Lipopolysaccharides / toxicity Liver / immunology Liver / pathology Male Methionine / administration & dosage Methionine / toxicity Mice Nanoparticles / chemistry Non-alcoholic Fatty Liver Disease / chemically induced Non-alcoholic Fatty Liver Disease / drug therapy* Non-alcoholic Fatty Liver Disease / immunology Non-alcoholic Fatty Liver Disease / pathology Pathogen-Associated Molecular Pattern Molecules / immunology Pathogen-Associated Molecular Pattern Molecules / metabolism Permeability RAW 264.7 Cells |
| IF | 1.863 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |