Effects of Extracts from Thai Piperaceae Plants against Infection with Toxoplasma gondii

Herbal medicines and natural herb extracts are widely used as alternative treatments for various parasitic diseases, and such extracts may also have potential to decrease the side effects of the standard regimen drugs used to treat toxoplasmosis (sulfadiazine-pyrimethamine combination). We evaluated how effective the Thai piperaceae plants Piper betle, P. nigrum and P. sarmentosum are against Toxoplasma gondii infection in vitro and in vivo. Individually, we extracted the piperaceae plants with ethanol, passed them through a rotary evaporator and then lyophilized them to obtain crude extracts for each one. The in vitro study indicated that the P. betle extract was the most effective extract at inhibiting parasite growth in HFF cells (IC50 on RH-GFP: 23.2 μg/mL, IC50 on PLK-GFP: 21.4 μg/mL). Furthermore, treatment of experimental mice with the P. betle extract for 7 days after infection with 1,000 tachyzoites of the T. gondii PLK strain increased their survival (survival rates: 100% in 400 mg/kg-treated, 83.3% in 100 mg/kg-treated, 33.3% in 25 mg/kg-treated, 33.3% in untreated mice). Furthermore, treatment with 400 mg/kg of the P. betle extract resulted in 100% mouse survival following infection with 100,000 tachyzoites. The present study shows that P. betle extract has the potential to act as a medical plant for the treatment of toxoplasmosis.

草药及天然植物提取物已被广泛用作多种寄生虫病的替代治疗方案，此类提取物或可降低治疗弓形虫病的标准联合用药方案——磺胺嘧啶-乙胺嘧啶——所带来的不良反应。本研究评估了泰国胡椒科（Piperaceae）植物蒌叶（Piper betle）、黑胡椒（Piper nigrum）与山蒟（Piper sarmentosum）在体内外对抗弓形虫（Toxoplasma gondii）感染的效果。我们分别采用乙醇提取上述胡椒科植物，经旋转蒸发仪浓缩后再进行冷冻干燥，从而获得各植物的粗提取物。体外实验结果显示，蒌叶提取物对HFF细胞内弓形虫增殖的抑制效果最为显著：针对RH-GFP虫株的半数抑制浓度（IC50）为23.2 μg/mL，针对PLK-GFP虫株的IC50为21.4 μg/mL。此外，在实验小鼠感染1000个弓形虫PLK株速殖子（tachyzoites）后，连续7天给予蒌叶提取物治疗，可提升小鼠存活率：400 mg/kg给药组存活率为100%，100 mg/kg给药组为83.3%，25 mg/kg给药组为33.3%，未给药对照组为33.3%。进一步实验显示，当小鼠感染10万个弓形虫速殖子后，以400 mg/kg剂量的蒌叶提取物进行治疗，可实现100%的小鼠存活率。本研究证实，蒌叶提取物具备开发为治疗弓形虫病药用植物制剂的潜力。