Combinatorial Treatment with Praziquantel and Curcumin Reduces Clonorchis sinensis Parasite Burden and Clonorchiasis-Associated Pathologies in Rats

<b>Background/Objectives</b>: 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 <i>C. sinensis</i> infection as well as its effect on ameliorating fibrotic tissue damage in rats. <b>Methods</b>: 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. <b>Results</b>: CUR+PZQ at LD₅₀ doses demonstrated a time- and dose-dependent antiparasitic effect in vitro, which was markedly greater than either drug alone. Rats were infected with <i>C. sinensis</i>, 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. <b>Conclusions</b>: Our findings indicate that CUR+PZQ co-treatment improved parasite clearance and promoted the resolution of hepatobiliary tissue damage resulting from chronic clonorchiasis.