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姜黄素负载纳米复合物可改善感染华支睾吸虫的仓鼠非酒精性脂肪性肝炎的严重程度。

Curcumin-loaded nanocomplexes ameliorate the severity of nonalcoholic steatohepatitis in hamsters infected with Opisthorchis viverrini.

机构信息

Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.

出版信息

PLoS One. 2022 Sep 27;17(9):e0275273. doi: 10.1371/journal.pone.0275273. eCollection 2022.

Abstract

BACKGROUND

Comorbidity of Opisthorchis viverrini (OV) infection and nonalcoholic fatty-liver disease (NAFLD) enhances NAFLD progression to nonalcoholic steatohepatitis (NASH) by promoting severe liver inflammation and fibrosis. Here, we investigated the effect of supplementation with curcumin-loaded nanocomplexes (CNCs) on the severity of NASH in hamsters.

METHODOLOGY

Hamsters were placed in experimental groups as follows: fed standard chow diet (normal control, NC); fed only high-fat and high-fructose (HFF) diet; O. viverrini-infected and fed HFF diet (HFFOV); group fed with blank nanocomplexes (HFFOV+BNCs); groups fed different doses of CNCs (25, 50 and 100 mg/kg body weight: HFFOV+CNCs25; HFFOV+CNCs50; HFFOV+CNCs100, respectively) and a group given native curcumin (HFFOV+CUR). All treatment were for three months.

RESULTS

The HFF group revealed NAFLD as evidenced by hepatic fat accumulation, ballooning, mild inflammation and little or no fibrosis. These changes were more obvious in the HFFOV group, indicating development of NASH. In contrast, in the HFFOV+CNCs50 group, histopathological features indicated that hepatic fat accumulation, cell ballooning, cell inflammation and fibrosis were lower than in other treatment groups. Relevantly, the expression of lipid-uptake genes, including fatty-acid uptake (cluster of differentiation 36), was reduced, which was associated with the lowering of alanine aminotransferase, total cholesterol and triglyceride (TG) levels. Reduced expression of an inflammation marker (high-mobility group box protein 1) and a fibrosis marker (alpha smooth-muscle actin) were also observed in the HFFOV+CNCs50 group.

CONCLUSION

CNCs treatment attenuates the severity of NASH by decreasing hepatic steatosis, inflammation, and fibrosis as well as TG synthesis. CNCs mitigate the severity of NASH in this preclinical study, which indicates promise for future use in patients.

摘要

背景

华支睾吸虫(OV)感染和非酒精性脂肪性肝病(NAFLD)的合并会通过促进严重的肝脏炎症和纤维化来增强 NAFLD 向非酒精性脂肪性肝炎(NASH)的进展。在这里,我们研究了负载姜黄素的纳米复合物(CNCs)补充剂对仓鼠 NASH 严重程度的影响。

方法

将仓鼠分为以下实验组:喂食标准的 Chow 饮食(正常对照组,NC);仅喂食高脂肪高果糖(HFF)饮食;感染华支睾吸虫并喂食 HFF 饮食(HFFOV);喂食空白纳米复合物(HFFOV+BNCs)组;喂食不同剂量的 CNCs(25、50 和 100mg/kg 体重:HFFOV+CNCs25、HFFOV+CNCs50、HFFOV+CNCs100)和喂食天然姜黄素组(HFFOV+CUR)。所有治疗均持续三个月。

结果

HFF 组表现出肝脂肪堆积、气球样变、轻度炎症和几乎没有纤维化的非酒精性脂肪肝,表明 NASH 的发展。相比之下,在 HFFOV+CNCs50 组中,组织病理学特征表明肝脂肪堆积、细胞气球样变、细胞炎症和纤维化低于其他治疗组。相关地,脂质摄取基因(包括脂肪酸摄取(分化群 36))的表达减少,这与丙氨酸氨基转移酶、总胆固醇和甘油三酯(TG)水平降低有关。在 HFFOV+CNCs50 组中还观察到炎症标志物(高迁移率族蛋白 B1)和纤维化标志物(α平滑肌肌动蛋白)的表达降低。

结论

CNCs 治疗通过减少肝脂肪变性、炎症和纤维化以及 TG 合成来减轻 NASH 的严重程度。CNCs 在这项临床前研究中减轻了 NASH 的严重程度,这表明在未来患者中具有应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8b/9514634/88d584f9fc79/pone.0275273.g001.jpg

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