School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China.
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China.
Int J Biol Macromol. 2021 Aug 31;185:338-349. doi: 10.1016/j.ijbiomac.2021.06.109. Epub 2021 Jun 24.
Chemical liver injury threatens seriously human health, along with the shortage of efficiency and low-toxicity drugs. Herein, the novel oral nanocomplexes composed of deoxycholic acid-grafted chitosan and oleanolic acid were constructed to reverse the CCl-induced acute liver damage in mice. Results indicated core-shell nanocomplexes, maintained by the hydrophobic interaction between deoxycholic acid and oleanolic acid, could be dissociated in the intestine. Notably, the nanocomplexes possessed superior hepatoprotective effect in vivo, possibly due to the synergistic effect between grafted chitosan and oleanolic acid. Mechanism investigations suggested that nanocomplexes reversed CCl-induced liver injury through improving hepatic antioxidant capacity via NrF2/Keap1 pathway and regulating inflammation response via NF-κB signaling pathway. The novel oral nanocomplexes represent an effective strategy for chemical liver injury therapy.
化学性肝损伤严重威胁人类健康，同时也存在疗效欠佳和低毒性药物缺乏的问题。本文构建了由去氧胆酸接枝壳聚糖和齐墩果酸组成的新型口服纳米复合物，以逆转 CCl 诱导的小鼠急性肝损伤。结果表明，由去氧胆酸和齐墩果酸之间的疏水相互作用维持的核壳纳米复合物可以在肠道中解离。值得注意的是，纳米复合物在体内具有优异的保肝作用，这可能是由于接枝壳聚糖和齐墩果酸的协同作用。机制研究表明，纳米复合物通过 NrF2/Keap1 通路改善肝抗氧化能力，通过 NF-κB 信号通路调节炎症反应，从而逆转 CCl 诱导的肝损伤。新型口服纳米复合物为化学性肝损伤治疗提供了一种有效的策略。
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