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穿心莲内酯的自纳米乳化给药:改善胰岛β细胞并抑制脂肪细胞分化

Self-nanoemulsifying Delivery of Andrographolide: Ameliorating Islet Beta Cells and Inhibiting Adipocyte Differentiation.

作者信息

Syukri Yandi, Taher Muhammad, Martien Ronny, Lukitaningsih Endang, Nugroho Agung Endro, Zakaria Zainul Amiruddin

机构信息

Department of Pharmacy, Islamic University of Indonesia, Yogyakarta, 55584, Indonesia.

Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Bandar Indera Mahkota, 25200, Kuantan, Pahang, Malaysia.

出版信息

Adv Pharm Bull. 2021 Jan;11(1):171-180. doi: 10.34172/apb.2021.018. Epub 2020 Nov 7.

Abstract

Insulin resistance is a characteristic of non-insulin-dependent diabetes mellitus associated with obesity and caused by the failure of pancreatic beta cells to secrete sufficient amount of insulin. Andrographolide (AND) improves beta-cell reconstruction and inhibits fat-cell formation. This research aimed to improve the delivery of water-insoluble AND in self-nanoemulsifying (ASNE) formulation, tested in streptozotocin (STZ)-induced diabetic rats and 3T3-L1 preadipocyte cells. A conventional formulation of AND in suspension was used as a control. The experimental rats were orally administered with self-nanoemulsifying (SNE) and suspension of AND for 8 days. Measurements were performed to evaluate blood glucose levels in preprandial and postprandial conditions. Immunohistochemistry was used to assess the process of islet beta cell reconstruction. In vitro study was performed using cell viability and adipocyte differentiation assay to determine the delivery of AND in the formulation. ASNE lowered blood glucose levels (day 4) faster than AND suspension (day 6). The histological testing showed that ASNE could regenerate pancreatic beta cells. Therefore, ASNE ameliorated pancreatic beta cells. The in vitro evaluation indicated the inhibition of adipocyte differentiation by both AND and ASNE, which occurred in a time-dependent manner. ASNE formulation had better delivery than AND. ASNE could improve the antidiabetic activity by lowering blood glucose levels, enhancing pancreatic beta cells, and inhibiting lipid formation in adipocyte cells.

摘要

胰岛素抵抗是与肥胖相关的非胰岛素依赖型糖尿病的一个特征,由胰腺β细胞无法分泌足够量的胰岛素所致。穿心莲内酯(AND)可改善β细胞重建并抑制脂肪细胞形成。本研究旨在改进水不溶性穿心莲内酯的自纳米乳化(ASNE)制剂的递送效果,并在链脲佐菌素(STZ)诱导的糖尿病大鼠和3T3-L1前脂肪细胞中进行测试。以穿心莲内酯的常规混悬液制剂作为对照。给实验大鼠口服穿心莲内酯的自纳米乳化制剂(SNE)和混悬液,持续8天。进行测量以评估餐前和餐后状态下的血糖水平。采用免疫组织化学法评估胰岛β细胞重建过程。通过细胞活力和脂肪细胞分化测定进行体外研究,以确定制剂中穿心莲内酯的递送情况。ASNE比穿心莲内酯混悬液更快降低血糖水平(第4天),而混悬液则在第6天降低血糖。组织学检测表明,ASNE可使胰腺β细胞再生。因此,ASNE改善了胰腺β细胞功能。体外评估表明,穿心莲内酯和ASNE均能抑制脂肪细胞分化,且呈时间依赖性。ASNE制剂的递送效果优于穿心莲内酯。ASNE可通过降低血糖水平、增强胰腺β细胞功能以及抑制脂肪细胞中的脂质形成来提高抗糖尿病活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a28c/7961231/29aff3ebdc8b/apb-11-171-g001.jpg

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