AUTHOR=El-Sayed Shimaa Abd El-Salam , El-Alfy El-Sayed , Sayed-Ahmed Mohamed Z. , Mohanta Uday Kumar , Alqahtani Saad S. , Alam Nawazish , Ahmad Sarfaraz , Ali Md Sajid , Igarashi Ikuo , Rizk Mohamed Abdo 

TITLE=Evaluating the inhibitory effect of resveratrol on the multiplication of several Babesia species and Theileria equi on in vitro cultures, and Babesia microti in mice

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1192999

DOI=10.3389/fphar.2023.1192999

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Histone post-translational modification is one of the most studied factors influencing epigenetic regulation of protozoan parasite gene expression, which is mediated by histone deacetylases (KDACs) and acetyltransferases (KATs).</p><p><bold>Objective and methods:</bold> The present study investigated the role of resveratrol (RVT) as an activator of histone deacetylases in the control of various pathogenic Babesia sp. and Theileria equi <italic>in vitro</italic>, as well as <italic>B. microti</italic> infected mice <italic>in vivo</italic> using fluorescence assay. Its role in mitigating the side effects associated with the widely used antibabesial drugs diminazene aceturate (DA) and azithromycin (AZM) has also been investigated.</p><p><bold>Results:</bold> The <italic>in vitro</italic> growth of <italic>B. bovis</italic>, <italic>B. bigemina</italic>, <italic>B. divergens</italic>, <italic>B. caballi</italic> and Theileria equi (<italic>T. equi</italic>) was significantly inhibited (P &lt; 0.05) by RVT treatments. The estimated IC50 values revealed that RVT has the greatest inhibitory effects on <italic>B. bovis</italic> growth <italic>in vitro</italic>, with an IC50 value of 29.51 ± 2.46 µM. Reverse transcription PCR assay showed that such inhibitory activity might be attributed to resveratrol’s stimulatory effect on <italic>B. bovis</italic> KDAC3 <italic>(BbKADC3)</italic> as well as its inhibitory effect on BbKATS. RVT causes a significant decrease (P &lt; 0.05) in cardiac troponin T (cTnT) levels in heart tissue of <italic>B. microti</italic>- infected mice, thereby indicating that RVT may play a part in reducing the cardiotoxic effects of AZM. Resveratrol showed an additive effect with imidocarb dipropionate <italic>in vivo</italic>. Treatment of <italic>B. microti</italic>-infected mice with a combined 5 mg/kg RVT and 8.5 mg/kg ID resulted in an 81.55% inhibition at day 10 postinoculation (peak of parasitemia).</p><p><bold>Conclusion:</bold> Our data show that RVT is a promising antibabesial pharmacological candidate with therapeutic activities that could overcome the side effects of the currently used anti-Babesia medications.</p>