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Article: Celastrol-loaded PEG-PCL nanomicelles ameliorate inflammation, lipid accumulation, insulin resistance and gastrointestinal injury in diet-induced obese mice

TitleCelastrol-loaded PEG-PCL nanomicelles ameliorate inflammation, lipid accumulation, insulin resistance and gastrointestinal injury in diet-induced obese mice
Authors
KeywordsObesity
Inflammation
Macrophage polarization
Celastrol
Nanomicelles
Issue Date2019
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jconrel
Citation
Journal of Controlled Release, 2019, v. 310, p. 188-197 How to Cite?
AbstractBotanical triterpene celastrol is a candidate drug for the treatment of obesity, except for concerns over the safety in clinical application. The present study was designed to investigate the anti-obesity, anti-inflammatory and toxic activities of celastrol-loaded nanomicelles (nano-celastrol) in diet-induced obese mice. Celastrol was loaded into PEG-PCL nanoparticles, yielding nano-celastrol with optimal size, spherical morphology, good bioavailability, slower peak time and clearance in mice. Nano-celastrol (5 or 7.5 mg/kg/d of celastrol) was administered into diet-induced obese C57BL/6 N male mice for 3 weeks. As result, higher dose nano-celastrol reduced body weight and body fat mass in an equally effective manner as regular celastrol, although lower dose nano-celastrol showed less activity. Similarly, nano-celastrol improved glucose tolerance in mice equally well as regular celastrol, whereas higher dose nano-celastrol improved the response to insulin. As for macrophage M1/M2 polarization in liver, nano-celastrol reduced the expression of macrophage M1 biomarkers (e.g., IL-6, IL-1β, TNF-α, iNOS) in a dose-dependent manner and marginally increased the expression of macrophage M2 biomarkers (e.g., Arg-1, IL-10). Moreover, celastrol could cause anus irritation and disturb intestinal and colonic integrity, whereas nano-celastrol did not cause any injury to mice. Collectively, nano-celastrol represents a translatable therapeutic opportunity for treating diet-induced obesity in humans.
Persistent Identifierhttp://hdl.handle.net/10722/276339
ISSN
2023 Impact Factor: 10.5
2023 SCImago Journal Rankings: 2.157
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhao, J-
dc.contributor.authorLuo, D-
dc.contributor.authorZhang, Z-
dc.contributor.authorFan, N-
dc.contributor.authorWang, Y-
dc.contributor.authorNie, H-
dc.contributor.authorRong, J-
dc.date.accessioned2019-09-10T03:01:06Z-
dc.date.available2019-09-10T03:01:06Z-
dc.date.issued2019-
dc.identifier.citationJournal of Controlled Release, 2019, v. 310, p. 188-197-
dc.identifier.issn0168-3659-
dc.identifier.urihttp://hdl.handle.net/10722/276339-
dc.description.abstractBotanical triterpene celastrol is a candidate drug for the treatment of obesity, except for concerns over the safety in clinical application. The present study was designed to investigate the anti-obesity, anti-inflammatory and toxic activities of celastrol-loaded nanomicelles (nano-celastrol) in diet-induced obese mice. Celastrol was loaded into PEG-PCL nanoparticles, yielding nano-celastrol with optimal size, spherical morphology, good bioavailability, slower peak time and clearance in mice. Nano-celastrol (5 or 7.5 mg/kg/d of celastrol) was administered into diet-induced obese C57BL/6 N male mice for 3 weeks. As result, higher dose nano-celastrol reduced body weight and body fat mass in an equally effective manner as regular celastrol, although lower dose nano-celastrol showed less activity. Similarly, nano-celastrol improved glucose tolerance in mice equally well as regular celastrol, whereas higher dose nano-celastrol improved the response to insulin. As for macrophage M1/M2 polarization in liver, nano-celastrol reduced the expression of macrophage M1 biomarkers (e.g., IL-6, IL-1β, TNF-α, iNOS) in a dose-dependent manner and marginally increased the expression of macrophage M2 biomarkers (e.g., Arg-1, IL-10). Moreover, celastrol could cause anus irritation and disturb intestinal and colonic integrity, whereas nano-celastrol did not cause any injury to mice. Collectively, nano-celastrol represents a translatable therapeutic opportunity for treating diet-induced obesity in humans.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jconrel-
dc.relation.ispartofJournal of Controlled Release-
dc.subjectObesity-
dc.subjectInflammation-
dc.subjectMacrophage polarization-
dc.subjectCelastrol-
dc.subjectNanomicelles-
dc.titleCelastrol-loaded PEG-PCL nanomicelles ameliorate inflammation, lipid accumulation, insulin resistance and gastrointestinal injury in diet-induced obese mice-
dc.typeArticle-
dc.identifier.emailZhao, J: zhaojia7@hku.hk-
dc.identifier.emailZhang, Z: zzhang01@hku.hk-
dc.identifier.emailWang, Y: yuwanghk@hku.hk-
dc.identifier.emailRong, J: jrong@hku.hk-
dc.identifier.authorityWang, Y=rp00239-
dc.identifier.authorityRong, J=rp00515-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jconrel.2019.08.026-
dc.identifier.pmid31454532-
dc.identifier.scopuseid_2-s2.0-85071581196-
dc.identifier.hkuros304954-
dc.identifier.volume310-
dc.identifier.spage188-
dc.identifier.epage197-
dc.identifier.isiWOS:000487856200016-
dc.publisher.placeNetherlands-
dc.identifier.issnl0168-3659-

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