Curcumin and Its Supramolecular Complex with Disodium Glycyrrhizinate as Potential Drugs for the Liver Fluke Infection Caused by <i>Opisthorchis felineus</i>
Maria N. Lvova,
Denis V. Ponomarev,
Alena A. Tarasenko,
Anna V. Kovner,
Galina A. Minkova,
Michail A. Tsyganov,
Meijun Li,
Yan Lou,
Veronica I. Evseenko,
Alexander V. Dushkin,
Irina V. Sorokina,
Tatiana G. Tolstikova,
Viatcheslav A. Mordvinov,
Damira F. Avgustinovich
Affiliations
Maria N. Lvova
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Denis V. Ponomarev
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Alena A. Tarasenko
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Anna V. Kovner
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Galina A. Minkova
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Michail A. Tsyganov
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Meijun Li
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia
Yan Lou
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia
Veronica I. Evseenko
Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Alexander V. Dushkin
Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Irina V. Sorokina
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Tatiana G. Tolstikova
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Viatcheslav A. Mordvinov
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Damira F. Avgustinovich
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
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 numbers of tumor-necrosis-factor-positive cells during the curcumin treatment and of kynurenine-3-monooxygenase-positive cells during the Cur:Na2GA treatment. A biochemical blood test revealed a normalizing effect of Cur:Na2GA (comparable to that of curcumin) on lipid metabolism. We believe that the further development and investigation of therapeutics based on curcuminoids in relation Opisthorchis felineus and other trematode infections will be useful for clinical practice and veterinary medicine.
