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Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A
Ning-Ke Guo1,2, Han She1, Lei Tan1
1State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, People's Republic of China.
International Journal of Nanomedicine
|February 23, 2023
Summary
Nano parthenolide (PTL) effectively treats sepsis-induced intestinal barrier dysfunction by reducing inflammation and improving survival. This novel nanoparticle formulation demonstrates superior therapeutic effects compared to ordinary PTL.
Area of Science:
- Biomedical Science
- Pharmacology
- Sepsis Research
Background:
- Sepsis frequently causes intestinal barrier dysfunction, a serious complication with limited treatment options.
- Parthenolide (PTL) shows promise for sepsis treatment, but the efficacy of its nanoformulation (Nano PTL) for intestinal barrier dysfunction remains unclear.
Purpose of the Study:
- To investigate the therapeutic potential of PTL and Nano PTL on sepsis-induced intestinal barrier dysfunction.
- To compare the protective effects of Nano PTL versus ordinary PTL in preclinical models of sepsis.
- To elucidate the underlying mechanism of PTL's action on the intestinal barrier.
Main Methods:
- Utilized cecal ligation and puncture (CLP) in rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) to model sepsis and intestinal barrier dysfunction.
- Synthesized and characterized Nano PTL, evaluating its encapsulation rate, drug loading, and cellular uptake.
- Employed network pharmacology and a serotonin 2A (5-HTR2A) inhibitor to explore the mechanism of action.
Main Results:
- Nano PTL exhibited high encapsulation (95±1.5%) and drug loading (11±0.5%), with excellent cellular uptake (94%).
- Both PTL and Nano PTL improved survival rates, prolonged survival time, reduced inflammatory cytokines, and preserved organ function in septic rats.
- In vitro, PTL and Nano PTL increased transepithelial electrical resistance (TEER) and decreased reactive oxygen species (ROS) and apoptosis in IECs, mediated via 5-HTR2A. Nano PTL demonstrated superior efficacy over ordinary PTL.
Conclusions:
- Both ordinary PTL and Nano PTL protect intestinal barrier function in sepsis by inhibiting apoptosis and ROS through upregulation of 5-HTR2A.
- Nano PTL offers enhanced therapeutic benefits compared to ordinary PTL for sepsis-induced intestinal barrier dysfunction.

