Torularhodin is a carotenoid that exerts beneficial effects on chronic kidney disease(CKD),which is strongly linked to a high-fat diet(HFD),however,its functional properties have not yet been fully determined.In this ...Torularhodin is a carotenoid that exerts beneficial effects on chronic kidney disease(CKD),which is strongly linked to a high-fat diet(HFD),however,its functional properties have not yet been fully determined.In this study,torularhodin bilosomes,which feature good processing properties and physical stability,were chosen for delivery.We evaluated their effect on mice with CKD induced by HFD and determined the relevant mechanisms.In HFD-fed mice,both structural and functional renal injury was observed,including significant increases in BUN,SCr,urinary protein levels,capillary basement membrane thickening,and inflammatory cell infiltration.The results showed that SOD content,GSH-px content,and CAT activity were all significantly higher,while the MDA level was significantly lower in the tor-emu and tor-bilo groups,indicating that torularhodin effectively alleviated oxidative stress.In addition,the expression of the inflammatory factors TNF-a,IL-6,and IL-1βwas reduced in the torularhodin group compared with the model group,and both the transcription and expression of the TLR4,MyD88,TIRAP,TRIF,and NF-κB proteins related to the TLR4/NF-κB pathway were reduced.Mechanistically,torularhodin reduced the renal inflammatory response by decreasing TLR4 protein expression and the signaling of proteins such as MyD88,as well as preventing NF-κB from undergoing dissociation,reducing its transcriptional activity,and decreasing the release of downstream pro-inflammatory mediators.In conclusion,torularhodin bilosomes can alleviate high-fat diet-induced CKD in mice by modulating the TLR4/NF-κB pathway.This result further deepens the understanding of torularhodin activity and confirms the role of torularhodin as an effective health supplement.展开更多
Oral administration is the most acceptable route of drug delivery at this stage due to its convenience,safety,and non-invasiveness.However,drugs given orally are exposed to a complex gastrointestinal environment,causi...Oral administration is the most acceptable route of drug delivery at this stage due to its convenience,safety,and non-invasiveness.However,drugs given orally are exposed to a complex gastrointestinal environment,causing a tremendous challenge for their successful absorption into the circulation.Over the past decades,researchers have developed various novel pharmaceutical technologies to improve oral absorption,among which the vesicular drug delivery system(like liposomes,niosomes and transfersomes)has received extensive attention.Encouragingly,there have been several investigations confirming the improved effect of vesicular drug delivery systems on oral drug absorption.Nevertheless,the clinical translation of oral vesicular drug delivery systems has been less impressive than implied by the positive results,and few vesicular formulations for oral use have been marketed yet.Against this background,this article provides an overview of the current applications and challenges associated with the vesicular delivery systems available for oral drug delivery,specifically liposomes,niosomes,transfersomes,chitosomes and bilosomes.The composition,formation mechanism,drug delivery advantages and application cases of these carriers in oral drug delivery are summarized.The possible mechanisms by which vesicular carriers enhance oral drug absorption are analyzed in terms of the in vivo process of oral drugs.Further,the challenges that oral vesicular carriers now face,such as safety,undefined in vivo fate,and scale-up production,are summarized,while possible strategies to deal with them are indicated.By reviewing the aforementioned,it can facilitate a more comprehensive knowledge of vesicular systems that can be used for oral drug delivery,providing a theoretical basis and reference for the design of oral formulations.展开更多
基金supported by the National Key Research and Development Program of China(Nos.2020YFC1606800)the Project funded by the Wuxi Taihu Lake Talent Plan.
文摘Torularhodin is a carotenoid that exerts beneficial effects on chronic kidney disease(CKD),which is strongly linked to a high-fat diet(HFD),however,its functional properties have not yet been fully determined.In this study,torularhodin bilosomes,which feature good processing properties and physical stability,were chosen for delivery.We evaluated their effect on mice with CKD induced by HFD and determined the relevant mechanisms.In HFD-fed mice,both structural and functional renal injury was observed,including significant increases in BUN,SCr,urinary protein levels,capillary basement membrane thickening,and inflammatory cell infiltration.The results showed that SOD content,GSH-px content,and CAT activity were all significantly higher,while the MDA level was significantly lower in the tor-emu and tor-bilo groups,indicating that torularhodin effectively alleviated oxidative stress.In addition,the expression of the inflammatory factors TNF-a,IL-6,and IL-1βwas reduced in the torularhodin group compared with the model group,and both the transcription and expression of the TLR4,MyD88,TIRAP,TRIF,and NF-κB proteins related to the TLR4/NF-κB pathway were reduced.Mechanistically,torularhodin reduced the renal inflammatory response by decreasing TLR4 protein expression and the signaling of proteins such as MyD88,as well as preventing NF-κB from undergoing dissociation,reducing its transcriptional activity,and decreasing the release of downstream pro-inflammatory mediators.In conclusion,torularhodin bilosomes can alleviate high-fat diet-induced CKD in mice by modulating the TLR4/NF-κB pathway.This result further deepens the understanding of torularhodin activity and confirms the role of torularhodin as an effective health supplement.
基金funded by the National Natural Science Foundation of China(No.81960717)the project of academic and technical leaders in major disciplines in Jiangxi Province(No.20212BCJL23060)+2 种基金the Guangxi science and technology base and talent project(No.Guike AD20238058)the Jiangxi University of Chinese Medicine science and technology innovation team development program(Nos.CXTD-22004,CXTD-22008)the PhD startup foundation of the Affiliated Hospital of Jiangxi University of Chinese Medicine(No.23KYQDZJ02)。
文摘Oral administration is the most acceptable route of drug delivery at this stage due to its convenience,safety,and non-invasiveness.However,drugs given orally are exposed to a complex gastrointestinal environment,causing a tremendous challenge for their successful absorption into the circulation.Over the past decades,researchers have developed various novel pharmaceutical technologies to improve oral absorption,among which the vesicular drug delivery system(like liposomes,niosomes and transfersomes)has received extensive attention.Encouragingly,there have been several investigations confirming the improved effect of vesicular drug delivery systems on oral drug absorption.Nevertheless,the clinical translation of oral vesicular drug delivery systems has been less impressive than implied by the positive results,and few vesicular formulations for oral use have been marketed yet.Against this background,this article provides an overview of the current applications and challenges associated with the vesicular delivery systems available for oral drug delivery,specifically liposomes,niosomes,transfersomes,chitosomes and bilosomes.The composition,formation mechanism,drug delivery advantages and application cases of these carriers in oral drug delivery are summarized.The possible mechanisms by which vesicular carriers enhance oral drug absorption are analyzed in terms of the in vivo process of oral drugs.Further,the challenges that oral vesicular carriers now face,such as safety,undefined in vivo fate,and scale-up production,are summarized,while possible strategies to deal with them are indicated.By reviewing the aforementioned,it can facilitate a more comprehensive knowledge of vesicular systems that can be used for oral drug delivery,providing a theoretical basis and reference for the design of oral formulations.
