CARNOSINE-LOADED ORAL NIOSOMES AMELIORATE HIGH-FRUCTOSE-INDUCED METABOLIC SYNDROME IN RATS VIA MODULATION OF SIRT1, A METABOLIC MASTER SWITCH

IF 0.3 4区 农林科学 Q4 VETERINARY SCIENCES Slovenian Veterinary Research Pub Date : 2023-02-26 DOI:10.26873/svr-1563-2022
Amany I. Ahmed, Nada Nasr, M. Said, Reham H. Alattar, K. El-Dawy
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引用次数: 0

Abstract

Metabolic syndrome is a crucial health challenge, and the available therapeutic agents are still not effective. Carnosine, a cytoplasmic dipeptide, is a potent anti-glycation, anti-oxidant, anti-inflammatory and chelating agent. However, whether carnosine would be assumed as a potential hypoglycemic agent or not, no decisive report with detailed mechanisms is found yet. As such, we suggest the carnosine-loaded in niosomes as a prospective solution to bypass its unwanted fast degradation by carnosinase which is considered as a major obstacle with the clinical application of carnosine as an oral drug therapy. Toward this, the purpose of our study is to assess the profits of oral administration of carnosine, and carnosine-loaded niosome in HFD-induced metabolic syndrome rats and to inspect some of the involved mechanisms. Initially, carnosine-loaded niosomes were prepared and characterized. Then, metabolic syndrome was provoked by 60% fructose diet in male Sprague Dawley rats where carnosine and carnosine-loaded niosomes were orally administered at doses 50 mg/kg and 25 mg/kg, respectively. In addition, biochemical and molecular studies were performed to clarify the possible mechanisms of action. Data showed that the consumption of 60% fructose diet displayed a tremendous increment in body weight, body mass index as well as a significant elevation in levels of serum glucose, insulin, TAG, TC, LDL-c, VLDL-c and FFA. Also, it showed a significant reduction in levels of serum HDL-c. Furthermore, HFD provoked up-regulation of SREBP-1c and FAS mRNA levels in adipose tissue. Also, it induced down-regulation of SIRT1, GLUT-4 mRNA levels in adipose tissue. We found that oral administration of either carnosine or carnosine-loaded niosome effectively reversed HFD-mediated alterations via SIRT1 activation. Overall, oral delivery of carnosine-loaded niosome had a better efficacy than oral carnosine, attenuating HFD-mediated alterations. Carnosine nano-formulation is a new excellent candidates for metabolic syndrome management and needs further exploration of its mechanisms.
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肌肽负载的口服小体通过调节代谢主开关sirt1改善大鼠高果糖诱导的代谢综合征
代谢综合征是一个至关重要的健康挑战,现有的治疗药物仍然无效。肌肽是一种细胞质二肽,是一种强效的抗糖基化、抗氧化、抗炎和螯合剂。然而,无论肌肽是否被认为是一种潜在的降血糖剂,目前还没有发现具有详细机制的决定性报告。因此,我们建议将肌肽装载在niosomes中作为一种前瞻性的解决方案,以绕过肌肽酶不必要的快速降解,肌肽酶被认为是肌肽作为口服药物治疗临床应用的主要障碍。为此,我们研究的目的是评估在HFD诱导的代谢综合征大鼠中口服肌肽和肌肽负载的niosome的利润,并检查一些相关机制。最初,制备并表征了肌肽负载的niosomes。然后,60%果糖饮食在雄性Sprague-Dawley大鼠中引发代谢综合征,其中分别以50mg/kg和25mg/kg的剂量口服肌肽和肌肽负载的肌体。此外,还进行了生化和分子研究,以阐明可能的作用机制。数据显示,摄入60%果糖饮食后,体重、体重指数显著增加,血糖、胰岛素、TAG、TC、LDL-c、VLDL-c和FFA水平显著升高。此外,它还显示出血清HDL水平的显著降低。此外,HFD引起脂肪组织SREBP-1c和FAS mRNA水平的上调。此外,它还诱导脂肪组织中SIRT1、GLUT-4 mRNA水平的下调。我们发现,口服肌肽或肌肽负载的niosome可通过SIRT1激活有效逆转HFD介导的改变。总的来说,口服肌肽负载的niosome比口服肌肽具有更好的疗效,减轻了HFD介导的改变。肌肽纳米制剂是代谢综合征治疗的一种新的优秀候选者,其机制有待进一步探索。
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来源期刊
Slovenian Veterinary Research
Slovenian Veterinary Research VETERINARY SCIENCES-
CiteScore
0.60
自引率
0.00%
发文量
12
审稿时长
>12 weeks
期刊介绍: SLOVENIAN VETERINARY RESEARCH (ISSN 1580-4003) publishes original articles, which report the results of original research in most areas of biomedicine. The journal also publishes review articles dealing with rapidly developing areas of biomedicine or which update understanding of classical fields of biomedicine, as well as case reports, shorter scientific contributions, letters to the editor, etc.; which have not been published or are under consideration for publication elsewhere. Only papers written in English can be considered.
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