Lee Soon-Ok, Chu Ki Back, Yoon Keon-Woong, Heo Su In, Song Jin-Ho, Li Jianhua, Hong Sung-Jong, Quan Fu-Shi
Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
Pharmaceutics. 2024 Dec 3;16(12):1550. doi: 10.3390/pharmaceutics16121550.
: Clonorchiasis is a foodborne parasitic disease that can lead to severe biliary fibrosis and cholangiocarcinoma. While praziquantel (PZQ) is available for clonorchiasis treatment, it cannot revert the histopathological damage incurred through parasite-induced fibrosis. Curcumin (CUR) is an emerging experimental drug possessing anti-inflammatory and fibrosis-alleviating effects, thus signifying its potential as an anthelmintic drug. Here, we evaluated the effect of CUR+PZQ combinatorial drug treatment on infection as well as its effect on ameliorating fibrotic tissue damage in rats. : Worm viabilities following CUR and PZQ treatments were confirmed through microscopy and tetrazolium salt absorption. Anthelminthic effect and hepatobiliary damage mitigation in rats were determined by quantifying worm recovery, histopathological staining, and enzyme-linked immunosorbent assay. : CUR+PZQ at LD doses demonstrated a time- and dose-dependent antiparasitic effect in vitro, which was markedly greater than either drug alone. Rats were infected with , and drugs were administered at 1 and 4 weeks post-infection (wpi) to assess drug-induced changes in worm burden. Significant reductions in worm burden recoveries were observed following CUR+PZQ treatment at both time points, accompanied by markedly reduced serum and mucosal IgG responses. ALT and AST levels were also substantially lower in combinatorial drug treatment groups than controls. Histopathological examinations confirmed that parasite-induced bile duct lumen widening and liver fibrosis were suppressed at 1 wpi, implying that CUR+PZQ co-treatment can alleviate clonorchiasis-associated pathologies. : Our findings indicate that CUR+PZQ co-treatment improved parasite clearance and promoted the resolution of hepatobiliary tissue damage resulting from chronic clonorchiasis.
华支睾吸虫病是一种食源性寄生虫病，可导致严重的胆管纤维化和胆管癌。虽然吡喹酮（PZQ）可用于治疗华支睾吸虫病，但它无法逆转由寄生虫引起的纤维化所导致的组织病理学损伤。姜黄素（CUR）是一种新兴的实验性药物，具有抗炎和减轻纤维化的作用，因此表明其作为驱虫药物的潜力。在此，我们评估了CUR+PZQ联合药物治疗对感染的影响以及对改善大鼠纤维化组织损伤的作用。通过显微镜检查和四氮唑盐吸收确认了CUR和PZQ处理后的虫体活力。通过量化虫体回收率、组织病理学染色和酶联免疫吸附测定来确定大鼠的驱虫效果和肝胆损伤减轻情况。LD剂量的CUR+PZQ在体外表现出时间和剂量依赖性的抗寄生虫作用，明显大于单独使用任何一种药物。大鼠感染[具体寄生虫名称未给出]，并在感染后1周和4周（wpi）给药，以评估药物引起的虫体负荷变化。在两个时间点进行CUR+PZQ治疗后，观察到虫体负荷回收率显著降低，同时血清和黏膜IgG反应明显降低。联合药物治疗组的ALT和AST水平也明显低于对照组。组织病理学检查证实，在1 wpi时，寄生虫引起的胆管管腔扩张和肝纤维化受到抑制，这意味着CUR+PZQ联合治疗可以减轻华支睾吸虫病相关的病理变化。我们的研究结果表明，CUR+PZQ联合治疗提高了寄生虫清除率，并促进了慢性华支睾吸虫病引起的肝胆组织损伤的消退。
