Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effect

Abstract In general, pseudoephedrine (PE) is a safe and universally employed in cold medicine, which displays powerful effect on antipyretic. Nonetheless, the sustained drug delivery system can effectively put an end to the above problems attributable to the drawbacks of low bioavailability and shor...

Full description

Saved in:
Bibliographic Details
Main Authors: Yuqin Yang, Jingyi Jiao, Xiaohui Jia, Lei Li, Meiling Wu, Xinyue Lu, Yangyang Sun, Yingqi Lang, Fuhao Chu, Dong Bai, Penglong Wang, Haimin Lei
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Nanobiotechnology
Online Access:https://doi.org/10.1186/s12951-025-03517-5
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849334308013080576
author Yuqin Yang
Jingyi Jiao
Xiaohui Jia
Lei Li
Meiling Wu
Xinyue Lu
Yangyang Sun
Yingqi Lang
Fuhao Chu
Dong Bai
Penglong Wang
Haimin Lei
author_facet Yuqin Yang
Jingyi Jiao
Xiaohui Jia
Lei Li
Meiling Wu
Xinyue Lu
Yangyang Sun
Yingqi Lang
Fuhao Chu
Dong Bai
Penglong Wang
Haimin Lei
author_sort Yuqin Yang
collection DOAJ
description Abstract In general, pseudoephedrine (PE) is a safe and universally employed in cold medicine, which displays powerful effect on antipyretic. Nonetheless, the sustained drug delivery system can effectively put an end to the above problems attributable to the drawbacks of low bioavailability and short intervals of administration. “Complexation” hydrogels are capturing enormous attention in a diverse array of fields in that there is no necessity to carry out external intervention for drug delivery. Nevertheless, it is prevalently acknowledged that macromolecular “complexation” hydrogels, biotin/avidin, antibodies/antigens, heterodimers, conA/glucose and cyclodextrin (CD) inclusion complexes, have several limitations of conventional drug delivery systems, such as unfavorable biological safety, undesirable intestinal wall penetrating, and extremely limited biodegradability, etc. For this reason, it is tremendously imperative to develop a natural small “complexation” hydrogel. In this context, we innovated a direct self-assembly “complexation” hydrogel (PE-GA). The PE-GA hydrogel was prepared by the incorporation of PE and glycyrrhizic acid (GA) into an aqueous dispersion without the aid of other carriers, which demonstrated dual-responsiveness including heating–cooling as well as pH. It is mainly governed by hydrogen bonds and electrostatic interactions. For cell bioavailability, there were substantial discrepancies between the PE-GA hydrogel and free PE at 72 and 84 h. For pharmacokinetic properties, there was also conspicuous discrepancy in Area Under the Curve (AUC) values between them. In subsequent antipyretic assay, PE-GA hydrogel displayed a conspicuous antipyretic effect in fever rats induced by LPS. The non-invasive fluorescence imaging was utilized to monitor the intestinal retention of the PE-GA hydrogel in mice, its unique aggregation/assembly induced retention (AIR) effect reinforced bioactive molecule retention, which may be another manifestation of enhancing antipyretic effect. Aside from that, PE-GA hydrogel played an antipyretic role by Hsp90/NF‐κB pathway. The current research revealed potential antipyretic effect of PE-GA hydrogel which could be the therapeutic option against fever. Graphical Abstract
format Article
id doaj-art-8379e352e627439d8eccb823201e0bbc
institution Kabale University
issn 1477-3155
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj-art-8379e352e627439d8eccb823201e0bbc2025-08-20T03:45:35ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123112010.1186/s12951-025-03517-5Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effectYuqin Yang0Jingyi Jiao1Xiaohui Jia2Lei Li3Meiling Wu4Xinyue Lu5Yangyang Sun6Yingqi Lang7Fuhao Chu8Dong Bai9Penglong Wang10Haimin Lei11Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical SciencesBeijing University of Chinese MedicineBeijing University of Chinese MedicineBeijing University of Chinese MedicineInstitute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical SciencesInstitute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical SciencesInstitute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical SciencesBeijing University of Chinese MedicineBeijing University of Chinese MedicineInstitute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical SciencesBeijing University of Chinese MedicineBeijing University of Chinese MedicineAbstract In general, pseudoephedrine (PE) is a safe and universally employed in cold medicine, which displays powerful effect on antipyretic. Nonetheless, the sustained drug delivery system can effectively put an end to the above problems attributable to the drawbacks of low bioavailability and short intervals of administration. “Complexation” hydrogels are capturing enormous attention in a diverse array of fields in that there is no necessity to carry out external intervention for drug delivery. Nevertheless, it is prevalently acknowledged that macromolecular “complexation” hydrogels, biotin/avidin, antibodies/antigens, heterodimers, conA/glucose and cyclodextrin (CD) inclusion complexes, have several limitations of conventional drug delivery systems, such as unfavorable biological safety, undesirable intestinal wall penetrating, and extremely limited biodegradability, etc. For this reason, it is tremendously imperative to develop a natural small “complexation” hydrogel. In this context, we innovated a direct self-assembly “complexation” hydrogel (PE-GA). The PE-GA hydrogel was prepared by the incorporation of PE and glycyrrhizic acid (GA) into an aqueous dispersion without the aid of other carriers, which demonstrated dual-responsiveness including heating–cooling as well as pH. It is mainly governed by hydrogen bonds and electrostatic interactions. For cell bioavailability, there were substantial discrepancies between the PE-GA hydrogel and free PE at 72 and 84 h. For pharmacokinetic properties, there was also conspicuous discrepancy in Area Under the Curve (AUC) values between them. In subsequent antipyretic assay, PE-GA hydrogel displayed a conspicuous antipyretic effect in fever rats induced by LPS. The non-invasive fluorescence imaging was utilized to monitor the intestinal retention of the PE-GA hydrogel in mice, its unique aggregation/assembly induced retention (AIR) effect reinforced bioactive molecule retention, which may be another manifestation of enhancing antipyretic effect. Aside from that, PE-GA hydrogel played an antipyretic role by Hsp90/NF‐κB pathway. The current research revealed potential antipyretic effect of PE-GA hydrogel which could be the therapeutic option against fever. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03517-5
spellingShingle Yuqin Yang
Jingyi Jiao
Xiaohui Jia
Lei Li
Meiling Wu
Xinyue Lu
Yangyang Sun
Yingqi Lang
Fuhao Chu
Dong Bai
Penglong Wang
Haimin Lei
Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effect
Journal of Nanobiotechnology
title Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effect
title_full Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effect
title_fullStr Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effect
title_full_unstemmed Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effect
title_short Natural small molecule smart hydrogels inhibited the Hsp90/NF‐κB signaling axis in inflammation to achieve sustained antipyretic effect
title_sort natural small molecule smart hydrogels inhibited the hsp90 nf κb signaling axis in inflammation to achieve sustained antipyretic effect
url https://doi.org/10.1186/s12951-025-03517-5
work_keys_str_mv AT yuqinyang naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT jingyijiao naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT xiaohuijia naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT leili naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT meilingwu naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT xinyuelu naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT yangyangsun naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT yingqilang naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT fuhaochu naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT dongbai naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT penglongwang naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect
AT haiminlei naturalsmallmoleculesmarthydrogelsinhibitedthehsp90nfkbsignalingaxisininflammationtoachievesustainedantipyreticeffect