Nanodrug rescues liver fibrosis via synergistic therapy with H(2)O(2) depletion and Saikosaponin b1 sustained release.
Nanodrug rescues liver fibrosis via synergistic therapy with H(2)O(2) depletion and Saikosaponin b1 sustained release.
复制标题
DOI：
10.1038/s42003-023-04473-2
复制
发表时间：
2023-02-16
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
缺氧和过氧化氢（H2 O2）积累形成促纤维化肝脏环境，其涉及肝星状细胞（HSC）的纤维化和慢性刺激。过氧化氢酶（CAT）是催化过氧化氢（H2 O2）生成氧和水的主要抗氧化酶，在不同的肝脏疾病尤其是肝纤维化中失去活性。本工作收集了肝硬化患者和肝纤维化小鼠的临床标本，结果表明，CAT降低与缺氧诱导的转化生长因子β1（TGF-β1）密切相关。一个多功能的纳米系统相结合的CAT样二氧化锰和抗纤维化柴胡皂苷b1（Ssb 1），随后构建抗纤维化治疗。MnO 2催化积累的H2 O2转化为氧气，从而改善缺氧和氧化应激，防止HSC活化，并有助于增强Ssb 1的抗纤维化药物作用。这项工作表明，TGF-β1是减少肝纤维化中CAT的原因，我们设计的MnO2@PLGA/Ssb 1纳米系统通过去除过量的H2 O2和缺氧应激而显示出增强的抗纤维化效率，这可能是一种有前途的治疗肝纤维化的治疗方法。通过结合CAT样MnO 2和抗纤维化柴胡皂苷b1的多功能纳米系统实现对肝脏的增强抗纤维化作用
Hypoxia and hydrogen peroxide (H2O2) accumulation form the profibrogenic liver environment, which involves fibrogenesis and chronic stimulation of hepatic stellate cells (HSCs). Catalase (CAT) is the major antioxidant enzyme that catalyzes H2O2 into oxygen and water, which loses its activity in different liver diseases, especially in liver fibrosis. Clinical specimens of cirrhosis patients and liver fibrotic mice are collected in this work, and results show that CAT decrease is closely correlated with hypoxia-induced transforminmg growth factor β1 (TGF-β1). A multifunctional nanosystem combining CAT-like MnO2 and anti-fibrosis Saikosaponin b1 (Ssb1) is subsequently constructed for antifibrotic therapy. MnO2 catalyzes the accumulated H2O2 into oxygen, thereby ameliorating the hypoxic and oxidative stress to prevent activation of HSCs, and assists to enhance the antifibrotic pharmaceutical effect of Ssb1. This work suggests that TGF-β1 is responsible for the diminished CAT in liver fibrosis, and our designed MnO2@PLGA/Ssb1 nanosystem displays enhanced antifibrotic efficiency through removing excess H2O2 and hypoxic stress, which may be a promising therapeutic approach for liver fibrosis treatment. Enhanced anti-fibrotic effect on the liver is achieved by a multifunctional nanosystem combining CAT-like MnO2 and anti-fibrosis Saikosaponin b1
登录
查看更多内容
影响因子：
16.6
作者：
Chen, Qi-Wen;Wang, Jia-Wei;Zhang, Xian-Zheng
通讯作者：
Zhang, Xian-Zheng
基于多成分药动学和代谢组学研究柴胡与白芍合用后植物化学物质药动学行为的变化及对内源代谢物的影响
影响因子：
5.6
作者：
Chen C;Yin Q;Tian J;Gao X;Qin X;Du G;Zhou Y
通讯作者：
Zhou Y
影响因子：
25.7
作者：
Asrani, Sumeet K.;Devarbhavi, Harshad;Kamath, Patrick S.
通讯作者：
Kamath, Patrick S.
影响因子：
3.1
作者：
Awad, Hanan;Nolette, Nora;Dakshinamurti, Shyamala
通讯作者：
Dakshinamurti, Shyamala
DOI：
10.1002/hep.31752
发表时间：
2021-06
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Dat NQ;Thuy LTT;Hieu VN;Hai H;Hoang DV;Thi Thanh Hai N;Thuy TTV;Komiya T;Rombouts K;Dong MP;Hanh NV;Hoang TH;Sato-Matsubara M;Daikoku A;Kadono C;Oikawa D;Yoshizato K;Tokunaga F;Pinzani M;Kawada N
通讯作者：
Kawada N