Efficacy assessment of miltefosine and curcumin against Clonorchis sinensis infection

Author:

Lee Soon-Ok1,Chu Ki Back23ORCID,Yoon Keon-Woong4,Eom Gi-Deok4,Mao Jie4,Lee Hyeryon5,No Joo Hwan5,Song Jin Ho6,Hong Sung-Jong7,Kim Sung Soo8,Quan Fu-Shi18ORCID

Affiliation:

1. Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea

2. Department of Parasitology, Inje University College of Medicine, Busan, Republic of Korea

3. Department of Infectious Disease and Malaria, Paik Institute of Clinical Research, Inje University, Busan, Republic of Korea

4. Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea

5. Host-Parasite Research Laboratory, Institut Pasteur Korea, Seongnam, Republic of Korea

6. Department Pharmacology, Chung-Ang University College of Medicine, Seoul, Republic of Korea

7. Convergence Research Center for Insect Vectors, Incheon National University, Incheon, Republic of Korea

8. Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea

Abstract

ABSTRACT Praziquantel (PZQ) is currently the only approved drug for treating clonorchiasis, but its poor efficacy against Clonorchis sinensis larvae has highlighted the need to develop newer drugs. In this study, to address this challenge, we investigated the anti-parasitic efficacy of miltefosine (MLT), curcumin (CUR), and PZQ against C. sinensis metacercariae (CsMC), newly excysted juvenile worms (CsNEJs), and adults. Larvicidal effects of MLT and CUR surpassed those elicited by PZQ in vitro . These two drugs exerted their effect against both CsMC and CsNEJs in a dose- and time-dependent manner. To confirm the effect of these drugs in vivo , Syrian golden hamsters were orally infected with 100 CsMC and subsequently treated with MLT, CUR, or PZQ at 1 and 4 weeks post-infection (wpi). MLT and CUR reduced the worm recoveries at 1 and 4 wpi, indicating that these drugs were efficacious against both larvae and adult C. sinensis . PZQ was only efficacious against adult worms. Interestingly, both MLT and CUR showed lower levels of C. sinensis- specific IgG responses than the infection control group, implying that worm burden and bile IgG responses could be correlated. These results indicate that MLT and CUR are efficacious against both larval and adult stages of C. sinensis , thereby highlighting their potential for further development as alternative therapeutic options for clonorchiasis.

Funder

National Research Foundation of Korea

Publisher

American Society for Microbiology

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