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槲皮素通过抑制骨关节炎模型大鼠基质金属蛋白酶-9、基质金属蛋白酶-13、含血小板反应蛋白基序的解聚素和金属蛋白酶-5的表达来预防蛋白聚糖破坏。

Quercetin prevent proteoglycan destruction by inhibits matrix metalloproteinase-9, matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs-5 expressions on osteoarthritis model rats.

作者信息

Permatasari Dian Agustina, Karliana Deantari, Iskandarsyah Iskandarsyah, Arsianti Ade, Bahtiar Anton

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.

Department of Pharmaceutics, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.

出版信息

J Adv Pharm Technol Res. 2019 Jan-Mar;10(1):2-8. doi: 10.4103/japtr.JAPTR_331_18.

Abstract

Prior study has shown that L. extract that containing quercetin has been proved to prevent inflammation and proteoglycan degradation by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase (MMP-9) expression. Target of osteoarthritis (OA) treatment was in the synovial joint that requiring a drug delivery system. The aim of this study was to prove the efficacy of quercetin-loaded lecithin-chitosan nanoparticles on the OA model rats by observed its effect on interleukin (IL-1) β, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) expressions. In this study, 70 white male Sprague Dawley rats were divided into 14 groups, 7 groups each for destabilization of medial meniscus (DMM) and monoiodoacetate (MIA)-induced OA. After 28 days from induction, SHAM and negative group received gel base topically; positive group received sodium diclofenac gel; three-dose group received each 0.84, 1.68, 3.36 mg/g quercetin-loaded nanoparticles gel; and L. group received L. extract gel. Each group gets treatment until day 70, and then, blood sample was collected for serum analysis; knee joint was isolated and subjected to histology samples treatment. Quercetin-loaded nanoparticle gel dose 1 (0.84 mg/g gel), dose 2 (1.68 mg/g gel), dose 3 (3.36 mg/g), and L. extract gel could decreased the level of IL-1 β, MMP-9, MMP-13, ADAMTS-5, and increasing color intensity significantly on histopathological observations on DMM and MIA-induced OA.

摘要

先前的研究表明,含有槲皮素的L.提取物已被证明可通过抑制肿瘤坏死因子-α和基质金属蛋白酶(MMP-9)的表达来预防炎症和蛋白聚糖降解。骨关节炎(OA)的治疗靶点位于滑膜关节,这需要一种药物递送系统。本研究的目的是通过观察槲皮素负载的卵磷脂-壳聚糖纳米颗粒对白细胞介素(IL-1)β、MMP-9、MMP-13和含血小板反应蛋白基序的解聚素和金属蛋白酶(ADAMTS-5)表达的影响,来证明其对OA模型大鼠的疗效。在本研究中,70只白色雄性Sprague Dawley大鼠被分为14组,每组7只,分别用于内侧半月板不稳定(DMM)和单碘乙酸(MIA)诱导的OA。诱导28天后,假手术组和阴性组局部给予凝胶基质;阳性组给予双氯芬酸钠凝胶;三剂量组分别给予每克含0.84、1.68、3.36毫克槲皮素的纳米颗粒凝胶;L.组给予L.提取物凝胶。每组治疗至第70天,然后采集血样进行血清分析;分离膝关节并进行组织学样本处理。在DMM和MIA诱导的OA的组织病理学观察中,含槲皮素的纳米颗粒凝胶剂量1(0.84毫克/克凝胶)、剂量2(1.68毫克/克凝胶)、剂量3(3.36毫克/克)和L.提取物凝胶可降低IL-1β、MMP-9、MMP-13、ADAMTS-5的水平,并显著增加颜色强度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2443/6383352/a12f36a67cab/JAPTR-10-2-g001.jpg

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