Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People's Republic of China.
Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
Int J Nanomedicine. 2023 Dec 27;18:7965-7983. doi: 10.2147/IJN.S430769. eCollection 2023.
The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect.
The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted.
The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the C was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration.
TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.
本研究前期阶段证实，一种包含 59%姜黄素（CU）、22%脱甲氧基姜黄素（DMC）和 18%双脱甲氧基姜黄素（BDMC）的姜黄提取物（TUR）可增强 CU 的稳定性，并具有更大的体外抗抑郁潜力。本研究的目的是开发一种包含 TUR 的纳米递药系统（TUR-NE），以改善 TUR 的药代动力学行为并增强其抗抑郁作用。
采用 ABTS、氧化应激诱导的细胞损伤和高通量筛选模型探讨 TUR 的抗抑郁潜力。制备、优化并表征 TUR-NE。口服给予正常大鼠后，评估 TUR-NE 的药代动力学行为。在慢性不可预测轻度应激模型（CUMS）小鼠中评估 TUR-NE 的抗抑郁作用。对小鼠的行为和生化指标进行了检测。
结果表明，TUR 的抗氧化能力分别比抗坏血酸和 CU 高 3.18 和 1.62 倍。与氟西汀和 CU 相比，TUR 对 ASP+转运的抑制作用明显增强。TUR-NE 的粒径为 116.0±0.31nm，多分散指数值为 0.121±0.007，包封率为 98.45%，在冷藏条件下具有良好的释放和稳定性。药代动力学结果表明，TUR-NE 的 AUC 分别是 CU 和 TUR 的 8.436 倍和 4.495 倍，而 C 分别是 CU 和 TUR 的 9.012 倍和 5.452 倍。药效学研究证实，TUR-NE 通过显著改善抑郁样行为和提高 CUMS 小鼠血浆和脑组织中 5-羟色胺的含量，具有更好的抗抑郁作用。TUR-NE 经重复给药后显示出良好的安全性。
TUR-NE 粒径小且均匀，提高了 TUR 的生物利用度和抗抑郁作用。它可能是一种有前途的新型抗抑郁口服制剂。
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