Curcumin and Its Supramolecular Complex with Disodium Glycyrrhizinate as Potential Drugs for the Liver Fluke Infection Caused by Opisthorchis felineus

作者：Maria Lvova, D. V. Ponomarev, Alena A. Tarasenko, А. В. Ковнер, Galina A. Minkova, М. А. Цыганов, Meijun Li, Yan Lou, V. I. Evseenko, Alexander V. Dushkin, И. В. Сорокина, Т. Г. Толстикова, Viatcheslav A. Mordvinov, Д. Ф. Августинович · 发表于：Pathogens · 年份：2023 · DOI：10.3390/pathogens12060819 · 被引用次数：9 · 研究领域：Curcumin's Biomedical Applications、Pharmacological Effects of Natural Compounds、Rabbits: Nutrition, Reproduction, Health

Opisthorchiosis is a parasitic liver disease found in mammals that is widespread throughout the world and causes systemic inflammation. Praziquantel remains the drug of choice for the treatment of opisthorchiosis, despite its many adverse effects. An anthelmintic effect is attributed to the main curcuminoid of Curcuma longa L. roots—curcumin (Cur)—along with many other therapeutic properties. To overcome the poor solubility of curcumin in water, a micellar complex of curcumin with the disodium salt of glycyrrhizic acid (Cur:Na2GA, molar ratio 1:1) was prepared via solid-phase mechanical processing. In vitro experiments revealed a noticeable immobilizing effect of curcumin and of Cur:Na2GA on mature and juvenile Opisthorchis felineus individuals. In vivo experiments showed that curcumin (50 mg/kg) had an anthelmintic effect after 30 days of administration to O. felineus-infected hamsters, but the effect was weaker than that of a single administration of praziquantel (400 mg/kg). Cur:Na2GA (50 mg/kg, 30 days), which contains less free curcumin, did not exert this action. The complex, just as free curcumin or better, activated the expression of bile acid synthesis genes (Cyp7A1, Fxr, and Rxra), which was suppressed by O. felineus infection and by praziquantel. Curcumin reduced the rate of inflammatory infiltration, whereas Cur:Na2GA reduced periductal fibrosis. Immunohistochemically, a decrease in liver inflammation markers was found, which is determined by calculating the numbe...