Rawat Aruna, Chauhan Samrat, Singh Rahul Pratap, Gupta Sumeet, Jhawat Vikas
Department of Pharmaceutical Science, School of Medical and Allied Science, GD Goenka University, Gurugram, Haryana India.
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab India.
In Silico Pharmacol. 2024 Sep 2;12(2):81. doi: 10.1007/s40203-024-00256-7. eCollection 2024.
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.
评估姜黄素标记的西洛他唑固体纳米分散体对Wistar大鼠链脲佐菌素-烟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）具有抑制作用，而姜黄素（Cur）是一种抗氧化剂和抗炎剂，且具有水溶性。采用“Box-Behnken设计”和乳液溶剂蒸发法制备固体纳米分散体，以提高其溶解度和生物利用度。链脲佐菌素（SPZ）和烟酰胺（NA）诱导Wistar大鼠患糖尿病。疾病诱导后30-45天发展为糖尿病肾病。所有大鼠组均接受了组织学、生化和药代动力学评估。优化后的载西洛他唑新型姜黄素标记固体纳米分散体（CLT-15 SND）批次在评估肾脏、脂质和细胞因子谱方面优于传统批次。与普通载西洛他唑固体纳米分散体（CLT-15 WC SND）相比，给糖尿病大鼠口服CLT-15 SND 45天，显著降低了空腹血糖水平和IL-6水平，并改善了脂质和肾脏指标以及体重。与CLT-15 WC和MP治疗动物组相比，CLT-15 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）分别改善了21.36%和18.36%，尿白蛋白水平分别改善了5.67%和14.19%，肌酐水平分别改善了3.125%和37.5%，血清尿素改善了30.48%，血清白蛋白分别增加了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、肾脏和脂质指标，证明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。
