Integrated animal experiments and network pharmacology for investigating therapeutic effect of celastrol-loaded liposomes on NAFLD.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current drug delivery Pub Date : 2023-08-10 DOI:10.2174/1567201821666230810094643

Jingbin Shi, Ninghui Ma, Ningchao Luo, Jingyi Huang, Shujun Xu, Yang Xiong

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Abstract

Background: The prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) is closely related to the increase of the incidence rate of obesity.

Aims: To find out the targets of celastrol on NAFLD with the treatment of celastrol-loaded liposomes (Cel-Lips).

Methods: Gene Expression Omnibus (GEO) data were used to compare the expression of differential genes in NAFLD patients with normal individuals. Celastrol was loaded into liposomes to improve its solubility, as well as, achieving a passive targeting effect on the liver to improve the availability, which also could delay the release rate of celastrol to prolong the action time and thus reduce the frequency of administration. Due to rarely reported molecular mechanisms of celastrol, with the help of network pharmacological analysis, the targets of celastrol acting on NAFLD were predictively analyzed.

Results: An association between NAFLD and lipid metabolism was detected in GEO data. Cel-Lips significantly alleviated NAFLD in vivo. Through network pharmacology, it was found that most of the action pathways of celastrol were related to lipid metabolism.

Conclusion: Celastrol has the potential to treat NAFLD, and its possible targets have been identified through network pharmacological screening, which provides a certain basis for the follow-up researches.

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结合动物实验和网络药理学研究了罗汉素脂质体对NAFLD的治疗作用。

背景:非酒精性脂肪性肝病(NAFLD)的患病率与肥胖发病率的增加密切相关。目的:探讨celastrol载脂质体(celastrol- lips)对NAFLD的治疗作用。方法:采用GEO (Gene Expression Omnibus)数据比较NAFLD患者与正常人差异基因的表达。将雷公藤红素加载到脂质体中，提高其溶解度，同时对肝脏产生被动靶向作用，提高利用度，同时延缓雷公藤红素的释放速度，延长作用时间，减少给药频率。由于celastrol的分子机制报道较少，借助网络药理学分析，对celastrol作用于NAFLD的靶点进行了预测分析。结果:在GEO数据中检测到NAFLD与脂质代谢之间的关联。cell - lips在体内显著缓解NAFLD。通过网络药理学研究发现，雷公藤红素的大部分作用途径与脂质代谢有关。结论:Celastrol具有治疗NAFLD的潜力，通过网络药理筛选确定了其可能的靶点，为后续研究提供了一定的依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current drug delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.10

自引率

4.20%

发文量

170

期刊介绍： Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves. The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance. The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.