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

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.

Resveratrol protects against Schistosoma mansoni-induced liver fibrosis by targeting the Sirt-1/NF-κB axis

“…In this study, we document an evident antifibrotic effect of resveratrol in schistosomal hepatic fibrosis and delineate some contributing mechanisms. In accordance with previous studies (Fang et al 2021 ) (El-Lakkany et al 2012 ), the untreated S. mansoni infected mice showed an elevation in serum levels of liver enzymes reflecting the loss of hepatocyte integrity, whereas the detected hypoalbuminemia could be the result of decreased albumin synthesis from damaged hepatocytes or due to decreased absorption from damaged intestinal mucosa (Al Humayed et al 2020 ; El-Lakkany et al 2012 ).…”

“…Therefore, prevention of fibrosis remains the only feasible strategy available (Kong et al 2020 ). Though very few agents (e.g., pirfenidone and nintedanib) have recently been approved for pulmonary fibrosis, an effective antifibrotic drug that can be used safely in liver fibrosis is considered a big challenge (Fang et al 2021 ). Therefore, promising plant-derived compounds possessing pleiotropic pharmacological actions with a long history of safety, such as resveratrol, merits attention (Koushki et al 2018 ).…”

“…This means that the likelihood of progression to hepatic fibrosis and cirrhosis still exists. Thus, to ensure liver protection against fibrosis and its subsequent complications, a combination of other (anti-fibrotic) drugs plus PZQ could be more advantageous than PZQ monotherapy (Fang et al 2021 ). Therefore, promising plant derived compounds like resveratrol with long history of safety merits attention.…”

Loss of GPR40 in LDL receptor-deficient mice exacerbates high-fat diet-induced hyperlipidemia and nonalcoholic steatohepatitis

“…These findings strongly suggest that although LFD is not associated with hyperlipidemia, the upregulation of CD36 by GPR40 KO increases lipid uptake and hepatic inflammation, contributing to hepatic steatosis, inflammation and fibrosis. Consistently, we showed that GPR40 KO in LFD-fed LDLR-deficient mice increased hepatic expression of aSMA, TGFβ1, IL-6 and TNFα, which are key molecules involved in hepatic fibrosis and inflammation [67,68].…”

Lactobacillus rhamnosus Encapsulated in Alginate/Chitosan Microgels Manipulates the Gut Microbiome to Ameliorate Salt-Induced Hepatorenal Injury

“…After sectioning, these tissues were assessed with hematoxylin and eosin (H&E) staining to observe the pathological changes under a microscope. In addition, the kidney and liver tissues were investigated by Masson staining to evaluate the histology of organ fibrosis, and the pathological scores of kidney and liver tissues were calculated per the method of Fang et al ( 31 ).…”