Muangnoi Chawanphat, Jithavech Ponsiree, Ratnatilaka Na Bhuket Pahweenvaj, Supasena Wiwat, Wichitnithad Wisut, Towiwat Pasarapa, Niwattisaiwong Nuansri, Haworth Ian S, Rojsitthisak Pornchai
a Natural Products for Ageing and Chronic Diseases Research Unit , Chulalongkorn University , Bangkok , Thailand.
b Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences , Chulalongkorn University , Bangkok , Thailand.
Biosci Biotechnol Biochem. 2018 Aug;82(8):1301-1308. doi: 10.1080/09168451.2018.1462694. Epub 2018 Apr 20.
In this work, a curcumin-diglutaric acid (CurDG) prodrug was synthesized by conjugation of curcumin with glutaric acid via an ester linkage. The water solubility, partition coefficient, release characteristics, and antinociceptive activity of CurDG were compared to those of curcumin. The aqueous solubility of CurDG (7.48 μg/mL) is significantly greater than that of curcumin (0.068 μg/mL). A study in human plasma showed that the CurDG completely releases curcumin within 2 h, suggesting the ability of CurDG to serve as a prodrug of curcumin. A hot plate test in mice showed the highest antinociceptive effect dose of curcumin at 200 mg/kg p.o., whereas CurDG showed the same effect at an effective dose of 100 mg/kg p.o., indicating that CurDG significantly enhanced the antinociceptive effect compared to curcumin. The enhanced antinociceptive effect of CurDG may be due to improved water solubility and increased oral bioavailability compared to curcumin.
在本研究中，通过姜黄素与戊二酸经酯键连接合成了姜黄素-戊二酸（CurDG）前药。将CurDG的水溶性、分配系数、释放特性和抗伤害感受活性与姜黄素进行了比较。CurDG的水溶性（7.48μg/mL）显著高于姜黄素（0.068μg/mL）。一项人体血浆研究表明，CurDG在2小时内完全释放出姜黄素，表明CurDG有能力作为姜黄素的前药。小鼠热板试验显示，姜黄素口服给药的最高抗伤害感受效应剂量为200mg/kg，而CurDG在100mg/kg口服有效剂量时表现出相同的效应，表明与姜黄素相比，CurDG显著增强了抗伤害感受效应。CurDG抗伤害感受效应增强可能是由于与姜黄素相比，其水溶性提高和口服生物利用度增加。
