Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A

Ning-Ke Guo,1,2,* Han She,1,* Lei Tan,1 Yuan-Qun Zhou,1 Chun-Qiong Tang,1 Xiao-Yong Peng,1 Chun-Hua Ma,1 Tao Li,1 Liang-Ming Liu1 1State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Research Institute of Surgery, Daping Hospital, Army Medical...

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Main Authors: Guo NK, She H, Tan L, Zhou YQ, Tang CQ, Peng XY, Ma CH, Li T, Liu LM
Format: Article
Language:English
Published: Dove Medical Press 2023-02-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/nano-parthenolide-improves-intestinal-barrier-function-of-sepsis-by-in-peer-reviewed-fulltext-article-IJN
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author Guo NK
She H
Tan L
Zhou YQ
Tang CQ
Peng XY
Ma CH
Li T
Liu LM
author_facet Guo NK
She H
Tan L
Zhou YQ
Tang CQ
Peng XY
Ma CH
Li T
Liu LM
author_sort Guo NK
collection DOAJ
description Ning-Ke Guo,1,2,* Han She,1,* Lei Tan,1 Yuan-Qun Zhou,1 Chun-Qiong Tang,1 Xiao-Yong Peng,1 Chun-Hua Ma,1 Tao Li,1 Liang-Ming Liu1 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; 2The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Li; Liang-Ming Liu, Email lt200132@163.com; lmliu62@tmmu.edu.cnBackground: Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured.Methods: In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis.Results: The encapsulation rate of Nano PTL was 95± 1.5%, the drug loading rate was 11± 0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL.Conclusion: Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.Keywords: sepsis, nano PTL, intestinal permeability, 5-HTR2A, apoptosis
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spelling doaj.art-2521b277146948678d71768333700b352023-02-12T17:45:33ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-02-01Volume 1869370981575Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2AGuo NKShe HTan LZhou YQTang CQPeng XYMa CHLi TLiu LMNing-Ke Guo,1,2,* Han She,1,* Lei Tan,1 Yuan-Qun Zhou,1 Chun-Qiong Tang,1 Xiao-Yong Peng,1 Chun-Hua Ma,1 Tao Li,1 Liang-Ming Liu1 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; 2The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Li; Liang-Ming Liu, Email lt200132@163.com; lmliu62@tmmu.edu.cnBackground: Intestinal barrier dysfunction is an important complication of sepsis, while the treatment is limited. Recently, parthenolide (PTL) has attracted much attention as a strategy of sepsis, but whether nano parthenolide (Nano PTL) is therapeutic in sepsis-induced intestinal barrier dysfunction is obscured.Methods: In this study, cecal ligation and puncture (CLP)-induced sepsis rats and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells (IECs) were used to investigate the effect of PTL on intestinal barrier dysfunction. Meanwhile, we synthesized Nano PTL and compared the protective effect of Nano PTL with ordinary PTL on intestinal barrier function in septic rats and IECs. Network pharmacology and serotonin 2A (5-HTR2A) inhibitor were used to explore the mechanism of PTL on the intestinal barrier function of sepsis.Results: The encapsulation rate of Nano PTL was 95± 1.5%, the drug loading rate was 11± 0.5%, and the average uptake rate of intestinal epithelial cells was 94%. Ordinary PTL and Nano PTL improved the survival rate and survival time of septic rats, reduced the mean arterial pressure and the serum level of inflammatory cytokines, and protected the liver and kidney functions in vivo, and increased the value of transmembrane resistance (TEER) reduced the reactive oxygen species (ROS) and apoptosis in IECs in vitro through 5-HTR2A. Nano PTL had better effect than ordinary PTL.Conclusion: Ordinary PTL and Nano PTL can protect the intestinal barrier function of septic rats by inhibiting apoptosis and ROS through up-regulating 5-HTR2A, Nano PTL is better than ordinary PTL.Keywords: sepsis, nano PTL, intestinal permeability, 5-HTR2A, apoptosishttps://www.dovepress.com/nano-parthenolide-improves-intestinal-barrier-function-of-sepsis-by-in-peer-reviewed-fulltext-article-IJNsepsisnano ptlintestinal permeability;5-htr2aapoptosis
spellingShingle Guo NK
She H
Tan L
Zhou YQ
Tang CQ
Peng XY
Ma CH
Li T
Liu LM
Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A
International Journal of Nanomedicine
sepsis
nano ptl
intestinal permeability;5-htr2a
apoptosis
title Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A
title_full Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A
title_fullStr Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A
title_full_unstemmed Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A
title_short Nano Parthenolide Improves Intestinal Barrier Function of Sepsis by Inhibiting Apoptosis and ROS via 5-HTR2A
title_sort nano parthenolide improves intestinal barrier function of sepsis by inhibiting apoptosis and ros via 5 htr2a
topic sepsis
nano ptl
intestinal permeability;5-htr2a
apoptosis
url https://www.dovepress.com/nano-parthenolide-improves-intestinal-barrier-function-of-sepsis-by-in-peer-reviewed-fulltext-article-IJN
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