Preclinical pharmacology and pharmacokinetics of curcumin tagged cilostazol nanodispersion for the management of diabetic nephropathy in wister rat model.

In silico pharmacology Pub Date : 2024-09-02 eCollection Date: 2024-01-01 DOI:10.1007/s40203-024-00256-7

Aruna Rawat, Samrat Chauhan, Monika, Rahul Pratap Singh, Sumeet Gupta, Vikas Jhawat

{"title":"Preclinical pharmacology and pharmacokinetics of curcumin tagged cilostazol nanodispersion for the management of diabetic nephropathy in wister rat model.","authors":"Aruna Rawat, Samrat Chauhan, Monika, Rahul Pratap Singh, Sumeet Gupta, Vikas Jhawat","doi":"10.1007/s40203-024-00256-7","DOIUrl":null,"url":null,"abstract":"To evaluate the therapeutic potential of curcumin tagged cilostazol solid nano dispersion in wistar rat streptozotocin-nicotinamide-induced diabetic nephropathy. Cilostazol (CLT), a Phosphodiesterase (PDE) inhibitor has an inhibitory effect on reactive oxygen species (ROS), and Curcumin (Cur), an antioxidant, and anti-inflammatory, are water-soluble. Solid Nano dispersions were developed using the \"Box-Behnken Design\" and emulsion solvent evaporation procedure to improve the solubility and bioavailability. Streptozotocin (SPZ) and Nicotinamide (NA) caused diabetes in Wistar rats. DN developed 30-45 days after disease induction. All rat groups underwent histological, biochemical and pharmacokinetic evaluation. The optimized batch of Cilostazol Loaded Novel Curcumin Tagged Solid Nanodispersion (CLT-15 SND) estimated renal, lipid, and cytokine profiles better than the conventional batch. CLT-15 SND, given orally to diabetic rats for 45 days, significantly lowered fasting BGL and IL-6 levels and improved lipid and kidney-profile markers and body weight compared to plain Cilostazol Loaded Solid Nanodispersion (CLT-15 WC SND). CLT-15 SND treatment groups showed decreased blood glucose by 3.38 and 9.71 percent, increased body weight by 2.81 and 5.27 percent, improved Interleukin-6 (IL-6) by 21.36 and 18.36 percent, improved urine albumin levels by 5.67 and 14.19 percent and creatinine levels by 3.125 and 37.5 percent, improved serum urea by 30.48 percent, increased serum albumin by 2.59 and 11.18 percent, and decreased creatinine and 5.03 and 8.12 percent, respectively as compared to CLT-15 WC and MP treatment animal groups. CLT and Cur reduced IL-6, kidney, and lipid markers, demonstrating their renoprotective and pancreas-protective effects. CLT and Cur's inhibition may be the mechanism.Graphical abstract: ","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368884/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"In silico pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40203-024-00256-7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

To evaluate the therapeutic potential of curcumin tagged cilostazol solid nano dispersion in wistar rat streptozotocin-nicotinamide-induced diabetic nephropathy. Cilostazol (CLT), a Phosphodiesterase (PDE) inhibitor has an inhibitory effect on reactive oxygen species (ROS), and Curcumin (Cur), an antioxidant, and anti-inflammatory, are water-soluble. Solid Nano dispersions were developed using the "Box-Behnken Design" and emulsion solvent evaporation procedure to improve the solubility and bioavailability. Streptozotocin (SPZ) and Nicotinamide (NA) caused diabetes in Wistar rats. DN developed 30-45 days after disease induction. All rat groups underwent histological, biochemical and pharmacokinetic evaluation. The optimized batch of Cilostazol Loaded Novel Curcumin Tagged Solid Nanodispersion (CLT-15 SND) estimated renal, lipid, and cytokine profiles better than the conventional batch. CLT-15 SND, given orally to diabetic rats for 45 days, significantly lowered fasting BGL and IL-6 levels and improved lipid and kidney-profile markers and body weight compared to plain Cilostazol Loaded Solid Nanodispersion (CLT-15 WC SND). CLT-15 SND treatment groups showed decreased blood glucose by 3.38 and 9.71 percent, increased body weight by 2.81 and 5.27 percent, improved Interleukin-6 (IL-6) by 21.36 and 18.36 percent, improved urine albumin levels by 5.67 and 14.19 percent and creatinine levels by 3.125 and 37.5 percent, improved serum urea by 30.48 percent, increased serum albumin by 2.59 and 11.18 percent, and decreased creatinine and 5.03 and 8.12 percent, respectively as compared to CLT-15 WC and MP treatment animal groups. CLT and Cur reduced IL-6, kidney, and lipid markers, demonstrating their renoprotective and pancreas-protective effects. CLT and Cur's inhibition may be the mechanism.

Graphical abstract:

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

姜黄素标记西洛他唑纳米分散体用于治疗威斯特大鼠模型糖尿病肾病的临床前药理学和药代动力学。

目的：评估姜黄素标记的西洛他唑固体纳米分散体对线粒体大鼠链脲佐菌素-尼古丁酰胺诱导的糖尿病肾病的治疗潜力。西洛他唑（CLT）是一种磷酸二酯酶（PDE）抑制剂，对活性氧（ROS）有抑制作用，姜黄素（Cur）是一种抗氧化剂和抗炎剂，均为水溶性。为了提高溶解度和生物利用度，我们采用 "Box-Behnken 设计 "和乳化溶剂蒸发程序开发了固体纳米分散体。链脲佐菌素（SPZ）和烟酰胺（NA）会导致 Wistar 大鼠患糖尿病。糖尿病诱导后 30-45 天出现 DN。所有大鼠组均接受了组织学、生物化学和药代动力学评估。与传统批次相比，优化批次的西洛他唑负载新型姜黄素标记固体纳米分散体（CLT-15 SND）能更好地评估肾脏、血脂和细胞因子状况。与普通的西洛他唑负载型固体纳米分散剂（CLT-15 WC SND）相比，糖尿病大鼠口服 CLT-15 SND 45 天后，空腹血糖胆固醇（BGL）和 IL-6 水平明显降低，血脂、肾轮廓指标和体重也有所改善。CLT-15 WC SND 治疗组的血糖分别降低了 3.38% 和 9.71%，体重分别增加了 2.81% 和 5.27%，白细胞介素-6（IL-6）分别提高了 21.36% 和 18.36%，尿白蛋白水平分别提高了 5.67% 和 14.19%，肌酐水平分别提高了 2.81% 和 5.27%。与 CLT-15 WC 和 MP 治疗动物组相比，尿白蛋白水平分别提高了 5.67% 和 14.19%，肌酐水平分别提高了 3.125% 和 37.5%，血清尿素分别提高了 30.48%，血清白蛋白分别提高了 2.59% 和 11.18%，肌酐分别降低了 5.03% 和 8.12%。CLT和Cur降低了IL-6、肾脏和血脂指标，显示了它们的肾脏保护和胰腺保护作用。CLT和Cur的抑制作用可能是其作用机制：

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

In silico pharmacology

自引率

0.00%

发文量