Issuriya Acharaporn, Cheaha Dania, Khan Muhammad, Panichayupakaranant Pharkphoom
Division of Biological Science, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90110, Thailand.
Biosignal Research Center for Health, Prince of Songkla University, Hat-Yai, Songkhla 90110, Thailand.
ACS Omega. 2025 Apr 5;10(14):14271-14282. doi: 10.1021/acsomega.5c00423. eCollection 2025 Apr 15.
The present study aimed to establish water-soluble curcuminoid-rich extracts and assess their acute and subchronic toxicities, following the OECD guidelines. Water-soluble curcuminoid-rich extracts, namely, CRE-Ter [ternary complex of curcuminoid-rich extract (CRE), hydroxypropyl-β-cyclodextrin, and polyvinylpyrrolidone K30] and CRE-SD (CRE in a solid dispersion form with polyvinylpyrrolidone K30) were produced via green technology, and their curcuminoid content was subsequently quantified using a high-performance liquid chromatographic (HPLC) method. CRE-Ter and CRE-SD contained 17.8% (w/w) total curcuminoids (12.7% (w/w) of curcumin, 3.2% (w/w) of demethoxycurcumin, and 1.9% (w/w) of bisdemethoxycurcumin) and 7.5% (w/w) total curcuminoids (5.2% (w/w) of curcumin, 1.4% (w/w) of demethoxycurcumin, and 0.9% (w/w) of bisdemethoxycurcumin), respectively. The acute and subchronic toxicities of the extracts were investigated in both male and female rats. The limit test of acute toxicity revealed that the oral LD of both CRE-Ter and CRE-SD was found to be greater than 2000 mg/kg, with no signs of acute toxicity or mortality during a single dose treatment of 2000 mg/kg. Similarly, regular oral administration of 0, 10, 30, and 300 mg/kg/day of CRE-Ter or CRE-SD for 90 days did not induce any significant toxicological effects on the clinical signs, body weights, food consumption, or water intake of both male and female rats. Moreover, no adverse effects were noted on the hematological or serum biochemical parameters. The gross appearance and histopathological analysis of the major visceral organs in treated groups were comparable to those of the control group. Interestingly, both CRE-Ter and CRE-SD significantly decreased the levels of lipid profiles and fasting blood glucose. These results clearly highlight the excellent safety profiles of CRE-Ter and CRE-SD when administered orally, paving the way for future drug development.
本研究旨在按照经合组织（OECD）指南制备富含水溶性姜黄素类化合物的提取物，并评估其急性和亚慢性毒性。通过绿色技术制备了富含水溶性姜黄素类化合物的提取物，即CRE-Ter [富含姜黄素类化合物的提取物（CRE）、羟丙基-β-环糊精和聚乙烯吡咯烷酮K30的三元复合物] 和CRE-SD（与聚乙烯吡咯烷酮K30形成固体分散体形式的CRE），随后使用高效液相色谱（HPLC）法对其姜黄素类化合物含量进行了定量。CRE-Ter和CRE-SD分别含有17.8%（w/w）的总姜黄素类化合物（12.7%（w/w）的姜黄素、3.2%（w/w）的去甲氧基姜黄素和1.9%（w/w）的双去甲氧基姜黄素）和7.5%（w/w）的总姜黄素类化合物（5.2%（w/w）的姜黄素、1.4%（w/w）的去甲氧基姜黄素和0.9%（w/w）的双去甲氧基姜黄素）。在雄性和雌性大鼠中研究了提取物的急性和亚慢性毒性。急性毒性的限度试验表明，CRE-Ter和CRE-SD的口服半数致死量均大于2000 mg/kg，在单次给予2000 mg/kg剂量治疗期间无急性毒性或死亡迹象。同样，以0、10、30和300 mg/kg/天的剂量对雄性和雌性大鼠定期口服CRE-Ter或CRE-SD 90天，对其临床体征、体重、食物消耗或饮水量均未产生任何显著的毒理学影响。此外，血液学或血清生化参数也未发现不良反应。治疗组主要内脏器官的大体外观和组织病理学分析与对照组相当。有趣的是，CRE-Ter和CRE-SD均显著降低了血脂水平和空腹血糖。这些结果清楚地表明，CRE-Ter和CRE-SD口服给药时具有出色的安全性，为未来的药物开发铺平了道路。
