Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice
Introduction: FLLL-32, a synthetic analog of curcumin, is a potent inhibitor of STAT3’s constitutive activation in a variety of cancer cells, and its anticancer properties have been demonstrated both in vitro and in vivo. It is also suggested that it might have other pharmacological activities inclu...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-11-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1278451/full |
| _version_ | 1827775417375784960 |
|---|---|
| author | Shimaa Abd El-Salam El-Sayed Shimaa Abd El-Salam El-Sayed El-Sayed El-Alfy Hanadi B. Baghdadi Hanadi B. Baghdadi Mohamed Z. Sayed-Ahmed Saad S. Alqahtani Nawazish Alam Sarfaraz Ahmad Md. Sajid Ali Ikuo Igarashi Mohamed Abdo Rizk |
| author_facet | Shimaa Abd El-Salam El-Sayed Shimaa Abd El-Salam El-Sayed El-Sayed El-Alfy Hanadi B. Baghdadi Hanadi B. Baghdadi Mohamed Z. Sayed-Ahmed Saad S. Alqahtani Nawazish Alam Sarfaraz Ahmad Md. Sajid Ali Ikuo Igarashi Mohamed Abdo Rizk |
| author_sort | Shimaa Abd El-Salam El-Sayed |
| collection | DOAJ |
| description | Introduction: FLLL-32, a synthetic analog of curcumin, is a potent inhibitor of STAT3’s constitutive activation in a variety of cancer cells, and its anticancer properties have been demonstrated both in vitro and in vivo. It is also suggested that it might have other pharmacological activities including activity against different parasites.Aim: This study therefore investigated the in vitro antiparasitic activity of FLLL-32 against four pathogenic Babesia species, B. bovis, B. bigemina, B. divergens, and B. caballi, and one Theileria species, Theileria equi. In vivo anti-Babesia microti activity of FLLL-32 was also evaluated in mice.Methods: The FLLL-32, in the growth inhibition assay with a concentration range (0.005–50 μM), was tested for it’s activity against these pathogens. The reverse transcription PCR (RT-PCR) assay was used to evaluate the possible effects of FLLL-32 treatment on the mRNA transcription of the target B. bovis genes including S-adenosylhomocysteine hydrolase and histone deacetylase.Results: The in vitro growth of B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi was significantly inhibited in a dose-dependent manner (in all cases, p < 0.05). FLLL-32 exhibits the highest inhibitory effects on B. bovis growth in vitro, and it’s IC50 value against this species was 9.57 μM. The RT-PCR results showed that FLLL-32 inhibited the transcription of the B. bovis S-adenosylhomocysteine hydrolase gene. In vivo, the FLLL-32 showed significant inhibition (p < 0.05) of B. microti parasitemia in infected mice with results comparable to that of diminazene aceturate. Parasitemia level in B. microti-infected mice treated with FLLL-32 from day 12 post infection (pi) was reduced to reach zero level at day 16 pi when compared to the infected non-treated mice.Conclusion: The present study demonstrated the antibabesial properties of FLLL-32 and suggested it’s usage in the treatment of babesiosis especially when utilized in combination therapy with other antibabesial drugs. |
| first_indexed | 2024-03-11T13:49:36Z |
| format | Article |
| id | doaj.art-d4774bbf31a941fc956290b40d3eb838 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-11T13:49:36Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d4774bbf31a941fc956290b40d3eb8382023-11-02T09:27:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-11-011410.3389/fphar.2023.12784511278451Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in miceShimaa Abd El-Salam El-Sayed0Shimaa Abd El-Salam El-Sayed1El-Sayed El-Alfy2Hanadi B. Baghdadi3Hanadi B. Baghdadi4Mohamed Z. Sayed-Ahmed5Saad S. Alqahtani6Nawazish Alam7Sarfaraz Ahmad8Md. Sajid Ali9Ikuo Igarashi10Mohamed Abdo Rizk11National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanDepartment of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptParasitology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptBiology Department, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaBasic and Applied Scientific Research Center (BASRC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, Jazan University, Jizan, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, Jazan University, Jizan, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, Jazan University, Jizan, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jazan University, Jizan, Saudi ArabiaNational Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, JapanDepartment of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, EgyptIntroduction: FLLL-32, a synthetic analog of curcumin, is a potent inhibitor of STAT3’s constitutive activation in a variety of cancer cells, and its anticancer properties have been demonstrated both in vitro and in vivo. It is also suggested that it might have other pharmacological activities including activity against different parasites.Aim: This study therefore investigated the in vitro antiparasitic activity of FLLL-32 against four pathogenic Babesia species, B. bovis, B. bigemina, B. divergens, and B. caballi, and one Theileria species, Theileria equi. In vivo anti-Babesia microti activity of FLLL-32 was also evaluated in mice.Methods: The FLLL-32, in the growth inhibition assay with a concentration range (0.005–50 μM), was tested for it’s activity against these pathogens. The reverse transcription PCR (RT-PCR) assay was used to evaluate the possible effects of FLLL-32 treatment on the mRNA transcription of the target B. bovis genes including S-adenosylhomocysteine hydrolase and histone deacetylase.Results: The in vitro growth of B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi was significantly inhibited in a dose-dependent manner (in all cases, p < 0.05). FLLL-32 exhibits the highest inhibitory effects on B. bovis growth in vitro, and it’s IC50 value against this species was 9.57 μM. The RT-PCR results showed that FLLL-32 inhibited the transcription of the B. bovis S-adenosylhomocysteine hydrolase gene. In vivo, the FLLL-32 showed significant inhibition (p < 0.05) of B. microti parasitemia in infected mice with results comparable to that of diminazene aceturate. Parasitemia level in B. microti-infected mice treated with FLLL-32 from day 12 post infection (pi) was reduced to reach zero level at day 16 pi when compared to the infected non-treated mice.Conclusion: The present study demonstrated the antibabesial properties of FLLL-32 and suggested it’s usage in the treatment of babesiosis especially when utilized in combination therapy with other antibabesial drugs.https://www.frontiersin.org/articles/10.3389/fphar.2023.1278451/fullFLLL-32BabesiaTheileria equiin vitroin vivo |
| spellingShingle | Shimaa Abd El-Salam El-Sayed Shimaa Abd El-Salam El-Sayed El-Sayed El-Alfy Hanadi B. Baghdadi Hanadi B. Baghdadi Mohamed Z. Sayed-Ahmed Saad S. Alqahtani Nawazish Alam Sarfaraz Ahmad Md. Sajid Ali Ikuo Igarashi Mohamed Abdo Rizk Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice Frontiers in Pharmacology FLLL-32 Babesia Theileria equi in vitro in vivo |
| title | Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice |
| title_full | Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice |
| title_fullStr | Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice |
| title_full_unstemmed | Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice |
| title_short | Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice |
| title_sort | antiparasitic activity of flll 32 against four babesia species b bovis b bigemina b divergens and b caballi and one theileria species theileria equi in vitro and babesia microti in mice |
| topic | FLLL-32 Babesia Theileria equi in vitro in vivo |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1278451/full |
| work_keys_str_mv | AT shimaaabdelsalamelsayed antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT shimaaabdelsalamelsayed antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT elsayedelalfy antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT hanadibbaghdadi antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT hanadibbaghdadi antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT mohamedzsayedahmed antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT saadsalqahtani antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT nawazishalam antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT sarfarazahmad antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT mdsajidali antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT ikuoigarashi antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice AT mohamedabdorizk antiparasiticactivityofflll32againstfourbabesiaspeciesbbovisbbigeminabdivergensandbcaballiandonetheileriaspeciestheileriaequiinvitroandbabesiamicrotiinmice |