In vivo Therapeutic Effects and Mechanisms of Hydroxyasiaticoside Combined With Praziquantel in the Treatment of Schistosomiasis Induced Hepatic Fibrosis.

Huilong Fang,Da You,Wanbei Guo,Junjie Wang,Xing Zhang,Ling Yu,Nan Peng

doi:10.3389/fbioe.2020.613784

Huilong Fang, Da You + Show 5 more

Open Access

https://doi.org/10.3389/fbioe.2020.613784

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Abstract

Schistosomiasis has been a fatal obstinate disease that threatens global human health, resulting in the granulomatous inflammation and liver fibrosis.Objective:The aim of this study was to evaluate the therapeutic effects and mechanisms of hydroxyasiaticoside combined with praziquantel in the treatment of schistosomiasis-induced liver fibrosis.Methods:Mice were randomly distributed into four experimental groups: normal control group, model group, praziquantel group, praziquantel + hydroxyasiaticoside group. Except for the normal control group, they were infected with Schistosomia cercariae through the abdominal skin to induce liver fibrosis. In the intervention group, mice were administered with the respective drugs by gavage after 8 weeks of infection. At the end of the treatment, mice were sacrificed to collect blood for the determination of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels. Moreover, the liver was excised, weighed, and liver indices were calculated. Histopathological examination was performed to assess liver morphology. Besides, the expression of collagen type I and III in liver was determined; the mRNA expression levels of IL-6 and TNF-α in liver tissues were measured using Real-time PCR while ELISA and western blotting were performed on liver tissue homogenate to determine the protein expression of IL-6 and TNF-α.Results:The combination of praziquantel and hydroxyasiaticoside lowered the pathological scores of schistosomiasis-induced hepatic fibrosis, the liver indice, serum AST and ALT levels, improved liver morphology, downregulated the expression levels of hepatic type I and III collagen, inhibited the mRNA expression levels of pro-inflammatory factors (IL-6 and TNF-α) in the liver of mice relative to the praziquantel alone.Conclusion:The combination of hydroxyasiaticoside and praziquantel is a potential therapeutic option for schistosomiasis-induced hepatic fibrosis. Notably, this combination noticeably suppresses the protein and mRNA expression levels of pro-inflammatory factors (TNF-α and IL-6) in the liver.

Highlights

In terms of public health impact, schistosomiasis is the second most important parasitic disease in the world (Tucker et al, 2013)
Hydroxyasiaticoside was extracted from C. asiatica by ethanol reflux method
The regression equation of the standard curve of hydroxyasiaticoside: Y = 282.96X-23.171, R2 = 0.9998, and the standard curve are shown in Supplementary Figure 1

Summary

Introduction

In terms of public health impact, schistosomiasis is the second most important parasitic disease in the world (Tucker et al, 2013). Liver fibrosis is a woundhealing process that is aimed at restoring organ integrity after mechanical stress, autoimmune reactions and infections induced severe injury. The solicitation of this process is pathogenic and a pathognomonic feature of diseases like schistosomiasis (Campana and Iredale, 2017; Aydin and Akçali, 2018; Parola and Pinzani, 2019). It has been reported that hydroxyasiaticoside has numerous significant biological effects, such as antiinflammation, anti-oxidation, anti-depression, anti-tumor, and anti-scar proliferation (Fitri et al, 2018a,b; Song et al, 2018; He et al, 2019). It has not been established whether hydroxy asiaticoside can alleviate schistosomiasisinduced fibrosis

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