Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders
文献类型： 外文期刊
作者： Jia, Ang 1 ; Jiang, Hongfei 2 ; Liu, Wenjing 2 ; Chen, Pengwei 3 ; Xu, Qi 4 ; Zhang, Renshuai 2 ; Sun, Jufeng 1 ;
作者机构： 1.Jinzhou Med Univ, Affiliated Hosp 1, Jinzhou 121000, Peoples R China
2.Qingdao Univ, Affiliated Hosp, Qingdao 266071, Peoples R China
3.Inst Trop Biosci & Biotechnol, Chinese Acad Trop Agr Sci, Hainan Key Lab Res & Dev Nat Prod Li Folk Med, Haikou 571101, Peoples R China
4.Qilu Univ Technol, Shandong Acad Sci, Shandong Anal & Test Ctr, Sch Pharmaceut Sci, Jinan 250353, Peoples R China
关键词： Dual inhibitors; Pancreatic triglyceride lipase; Cinaciguat; Gut microbiota
期刊名称：PHARMACOLOGICAL RESEARCH （ 影响因子：9.3； 五年影响因子：8.8 ）
ISSN： 1043-6618
年卷期： 2023 年 194 卷
页码：
收录情况： SCI
摘要： Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge. Pancreatic triglyceride lipase (PTL) and Niemann-Pick C1-like 1 (NPC1L1) have been identified as crucial proteins in the transport of triglycerides and cholesterol. Here, cinaciguat, a known agent used in the treatment of acute decompensated heart failure, was identified as a potent dual inhibitor targeting PTL and NPC1L1. We presented in vitro evidence from surface plasmon resonance analysis that cinaciguat interacted with PTL and NPC1L1. Furthermore, cinaciguat exhibited potent PTL-inhibition activity. Fluorescence-labeled cholesterol uptake analysis and confocal imaging showed that cinaciguat effectively inhibited cholesterol uptake. In vivo evaluation showed that cinaciguat significantly reduced the plasma levels of triglycerides and cholesterol, and effectively alleviated high-fat diet-induced intestinal microbiota dysbiosis and metabolic disorders. These results collectively suggest that cinaciguat has the potential to be further developed for the therapy of mixed hyperlipidemia.
- 相关文献
作者其他论文 更多>>
-
Identification of targets and comparative study of administration methods for the lipid-lowering effects of fucoidan from Saccharina japonica
作者：Chen, Pengwei;Wang, Hao;Chen, Huiqin;Dai, Haofu;Hao, Li;Li, Quancai;Zhang, Miao;Jiang, Hongfei;Zhang, Renshuai;Jia, Ang
关键词：Fucoidan; Lipid-lowering activity; Dietary supplementation; Intestinal target; Gut microbiota
-
The genomic and epigenomic landscapes of hemizygous genes across crops with contrasting reproductive systems
作者：Peng, Yanling;Wang, Yiwen;Liu, Yuting;Fang, Xinyue;Cheng, Lin;Long, Qiming;Su, Dalu;Zhang, Tianhao;Shi, Xiaoya;Xu, Xiaodong;Xu, Qi;Wang, Nan;Zhang, Fan;Liu, Zhongjie;Xiao, Hua;Huang, Sanwen;Zhou, Yongfeng;Yao, Jin;Tian, Ling;Hu, Wei;Chen, Songbi;Huang, Sanwen;Zhou, Yongfeng;Wang, Haibo;Gaut, Brandon S.
关键词：grapevine; clonal propagation; structural variation; integrative genomics; heterozygosity
-
Interaction of R2R3-MYB transcription factor EgMYB111 with ABA receptors enhances cold tolerance in oil palm
作者：Zhou, Lixia;Li, Rui;Yang, Xuanwen;Yang, Yaodong;Zhou, Yongfeng;Zhou, Lixia;Li, Rui;Yang, Yaodong;Iqbal, Amjad;Yang, Xuanwen;Peng, Yanling;Wang, Yiwen;Xu, Qi;Su, Xiangnian;Zhou, Yongfeng;Wang, Yiwen;Iqbal, Amjad
关键词：Elaeis guineensis; Oil palm; MYB transcription factors; EgMYB111; ABA signaling pathway; Cold tolerance
-
Mango pangenome reveals dramatic impacts of reference bias on population genomic analyses
作者：Ahmad, Bilal;Su, Ying;Hao, Yani;Razzaq, Tayyaba;Arshad, Rida;Zhang, Yi;Zhang, Yingchun;Wang, Xingyi;Huang, Guizhou;Su, Xiangnian;Hou, Ting;Yang, Xuanwen;Xu, Qi;Xu, Xiaodong;Peng, Yanling;Xiao, Hua;Zhou, Yongfeng;Su, Ying;Chu, Zhenzhou;Tian, Xinmin;Hao, Yani;Wang, Xingyi;Li, Chaochao;Jin, Zhongxin;Xu, Xiaodong;Bi, Guiqi;Chen, Chengjie;Huang, Jianfeng;Zhou, Yongfeng;Li, Chuanning;Chu, Zhenzhou;Wang, Qiuyan;Tian, Xinmin;Li, Chuanning;Chu, Zhenzhou;Wang, Qiuyan;Tian, Xinmin;Zhang, Yu;Chen, Yeyuan
关键词：
-
Deep learning empowers genomic selection of pest-resistant grapevine
作者：Gan, Yu;Liu, Zhenya;Zhang, Fan;Wang, Xu;Xue, Hui;Su, Xiangnian;Xu, Xiaodong;Li, Chaochao;Yang, Xuanwen;Wei, Pengcheng;Zhou, Lianzhu;Wang, Yiwen;Liu, Zhongjie;Zhou, Yongfeng;Gan, Yu;Liu, Zhenya;Zhang, Fan;Xu, Qi;Wang, Xu;Xue, Hui;Su, Xiangnian;Ma, Wenqi;Long, Qiming;Ma, Anqi;Huang, Guizhou;Liu, Wenwen;Xu, Xiaodong;Zhang, Yingchun;Liu, Yuting;Fang, Xinyue;Li, Chaochao;Yang, Xuanwen;Zhou, Lianzhu;Wang, Yiwen;Sun, Lei;Fan, Xiucai;Liu, Chonghuai;Zhang, Chuan;Zhang, Zhiwu;Wei, Pengcheng;Gan, Yu;Liu, Zhongjie
关键词：
-
Molecular evolution and characterization of type III polyketide synthase gene family in Aquilaria sinensis
作者：Ding, Xupo;Wang, Hao;Huang, Shengzhou;Zhang, Hao;Chen, Huiqin;Chen, Pengwei;Yang, Zhuo;Peng, Shiqing;Dai, Haofu;Mei, Wenli;Ding, Xupo;Wang, Hao;Huang, Shengzhou;Chen, Huiqin;Chen, Pengwei;Wang, Yuguang;Wang, Yali;Dai, Haofu;Mei, Wenli;Ding, Xupo;Huang, Shengzhou;Chen, Huiqin;Chen, Pengwei;Wang, Yuguang;Wang, Yali;Dai, Haofu;Mei, Wenli;Ding, Xupo;Dai, Haofu;Mei, Wenli
关键词：Polyketide synthase; 2-(2-Phenylethyl) chromone biosynthesis; Agarwood; Evolution; Transient expression
-
Doxorubicin prodrug-based nanomedicines for the treatment of cancer
作者：Zhao, Haibo;Zhang, Renshuai;Jiang, Hongfei;Yu, Jing;Chen, Pengwei;Yu, Wanpeng
关键词：Doxorubicin; Prodrug; Nanomedicine; Stimuli responsive; Cancer therapy; Antitumor
