一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Molecular Pharmaceutics >>article
Molecular Pharmaceutics

Molecular Pharmaceutics

IF: 4.5
Download PDF

Reactive Oxygen Species-Responsive Delivery of a Notch Inhibitor to Alleviate Nonalcoholic Steatohepatitis by Inhibiting Hepatic de Novo Lipogenesis and Inflammation

Published:15 May 2024 DOI: 10.1021/acs.molpharmaceut.4c00070 PMID: 38751169
Jiahao Chen, Jinhang Zhang, Yan Xia, Jiahui Li, Qingyi Jia, Zijing Zhang, Xiandan Jing, Ying Xu, Ling Zou, Lingling Wang, Haiying Song, Jingwei Li, Qinhui Liu, Yimin Xiong, Qin Tang, Wenfei Chen, Na Yang, Haixia Xu, Yanping Li* and Jinhan He*, 

Abstract

With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to H2O2, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Iminostilbene 256-96-2 C14H11N 352 suppliers $5.00-$1543.65
Iminostilbene 256-96-2 C14H11N 352 suppliers $5.00-$1543.65
Iminostilbene 256-96-2 C14H11N 352 suppliers $5.00-$1543.65
Iminostilbene 256-96-2 C14H11N 352 suppliers $5.00-$1543.65
祁阳县| 额尔古纳市| 象山县| 香港 | 鹿邑县| 天水市| 米泉市| 韶山市| 务川| 金堂县| 金坛市| 盖州市| 吴江市| 海南省| 安顺市| 泽普县| 大洼县| 津南区| 西丰县| 姜堰市| 上虞市| 白山市| 临漳县| 浦东新区| 汉川市| 松滋市| 铜陵市| 玛曲县| 合肥市| 慈溪市| 磐石市| 肥西县| 施甸县| 卢湾区| 柘荣县| 泰安市| 新郑市| 隆化县| 凤山市| 新干县| 分宜县|