Botanical Medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia Demonstrate Inhibitory Activity Against Babesia duncani.

Yumin Zhang,Hector Alvarez-Manzo,Ying Zhang,Jacob Leone,Sunjya Schweig

doi:10.3389/fcimb.2021.624745

Abstract

Human babesiosis is a CDC reportable disease in the United States and is recognized as an emerging health risk in multiple parts of the world. The current treatment for human babesiosis is suboptimal due to treatment failures and unwanted side effects. Although Babesia duncani was first described almost 30 years ago, further research is needed to elucidate its pathogenesis and clarify optimal treatment regimens. Here, we screened a panel of herbal medicines and identified Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Alchornea cordifolia, and Polygonum cuspidatum to have good in vitro inhibitory activity against B. duncani in the hamster erythrocyte model. Furthermore, we found their potential bioactive compounds, cryptolepine, artemisinin, artesunate, artemether, and baicalein, to have good activity against B. duncani, with IC50 values of 3.4 μM, 14 μM, 7.4 μM, 7.8 μM, and 12 μM, respectively, which are comparable or lower than that of the currently used drugs quinine (10 μM) and clindamycin (37 μM). B. duncani treated with cryptolepine and quinine at their respective 1×, 2×, 4× and 8× IC50 values, and by artemether at 8× IC50 for three days could not regrow in subculture. Additionally, Cryptolepis sanguinolenta 90% ethanol extract also exhibited no regrowth after 6 days of subculture at doses of 2×, 4×, and 8× IC50 values. Our results indicate that some botanical medicines and their active constituents have potent activity against B. duncani in vitro and may be further explored for more effective treatment of babesiosis.

Highlights

Babesiosis is a disease caused by the Babesia parasite that infects red blood cells
Cryptolepis sanguinolenta (60, 90% ethanol extracts), Artemisia annua (30% ethanol extract), Scutellaria baicalensis (60%, 90% ethanol extracts), Polygonum cuspidatum (60% ethanol extract), and Alchornea cordifolia were the top hits with more than 50%
The results showed that Artemisia annua (30% ethanol extract) and Scutellaria baicalensis (90% ethanol extract) treated B. duncani could regrow at 1×, 2×, 4×, and 8× IC50 values, and growth of most of these treated parasites could be observed at day two (Figures 4A, B)

Summary

Introduction

Babesiosis is a disease caused by the Babesia parasite that infects red blood cells. Babesia microti, and Babesia duncani cause the most human babesiosis cases worldwide. Most human babesiosis infections in the United States are caused by B. microti and B. duncani, and in Europe the majority of reported cases are due to B. divergens (Vannier and Krause, 2012). All of these Babesia species can be acquired by Ixodes ticks that are reservoirs of Borrelia spirochetes which cause Lyme disease. On immunosuppressive therapies, and those who have undergone splenectomy are at increased risk of more severe symptoms and even death (Vannier et al, 2015)

Methods

Results

Discussion

Conclusion