Corilagin Counteracts IL-13Rα1 Signaling Pathway in Macrophages to Mitigate Schistosome Egg-Induced Hepatic Fibrosis

Abstract

The IL-13Rα1 signaling pathway and M2 macrophages play crucial roles in schistosome egg-induced hepatic fibrosis via the expression of pro-fibrotic molecules. This study aims to investigate the inhibitory effect and mechanism of action of corilagin on schistosome egg-induced hepatic fibrosis via the IL-13Rα1 signaling pathway in M2 macrophages in vitro and in vivo. The mRNA and protein expression of IL-13Rα1, PPARγ, KLF4, SOCS1, STAT6, p-STAT6, and TGF-β was measured in vitro with corilagin treatment after IL-13 stimulation and in vivo corilagin treatment after effectively killing the adult schistosomes in schistosome-infected mice. Histological analysis of liver tissue was assessed for the degree of hepatic fibrosis. The results revealed that corilagin significantly reduced the expression of PPARγ, KLF4, SOCS1, p-STAT6, and TGF-β compared with model group and praziquantel administration (p < 0.01 or p < 0.05) in vivo and in vitro, which indicated a strong inhibitory effect of corilagin on IL-13Rα1 signaling pathway. As well, the inhibitory effect of corilagin showed a significant dose-dependence (p < 0.05). The area of fibrosis and distribution of M2 macrophages in mouse liver tissue were reduced significantly and dose-dependently with corilagin treatment compared to model group or praziquantel administration (p < 0.01 or p < 0.05), indicating that corilagin suppressed IL-13Rα1 signaling pathway and M2 macrophage polarization effectively in vivo. Furthermore, the anti-fibrogenic effect persisted even when IL-13Rα1 was up- or down-regulated in vitro. In conclusion, corilagin can suppress schistosome egg-induced hepatic fibrosis via inhibition of M2 macrophage polarization in the IL-13Rα1 signaling pathway.

Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models

“…Our present study now reconcile such observations, demonstrating that PZQ has potential preventive antifibrotic effects while it has no efficacy in therapeutically reversing established fibrosis. This conclusion reliably recapitulates the established view of most authors on the subject 9,11,21,[53][54][55][56][57][58][59][60][61][62][63] where PZQ antifibrotic / anti-pathological potential in clinically fibrotic schistosomiasis-diseased patients might not be direct and/or effective on established fibrosis but entirely consequent to its anti-parasitic effect when administered after fibrosis development.…”

“…The extensive usage of PZQ during mass drug administration campaigns in flatworm-endemic areas has considerable health benefits for the target populations over time such as improved fitness, improved cognitive functions and reduced tissue fibrosis 13,[15][16][17][18][19][20]34,[40][41][42][43][44][45][46][47][48][49][50][51][52] . Whereas most authors associated such health benefits and particularly the improvement of tissue fibrosis in helminth-infested individuals to the sole antiparasitic potential of PZQ 9,11,21,[53][54][55][56][57][58][59][60][61][62][63] , recent reports on the drug ability to also directly mitigate tissue fibrosis have also emerged 13,[15][16][17][18][19][20]34,[40][41][42][43]…”

Corilagin Alleviates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced C57BL/6 Mice by Ameliorating Oxidative Stress and Restoring Autophagic Flux

“…Particularly, the hepatoprotective effect of Cori has been brought into focus by current research. Several studies reported the protective role of Cori against hepatocellular carcinoma (HCC) (Ming et al, 2013), hepatic injury following hemorrhagic shock (Liu et al, 2017), schistosomiasis hepatic fibrosis (Li et al, 2017), and hepatitis c virus (HCV) infection (Reddy et al, 2018). However, whether Cori possesses the therapeutic potential for the treatment of NAFLD has not been reported yet.…”

Corilagin Ameliorates Atherosclerosis in Peripheral Artery Disease via the Toll-Like Receptor-4 Signaling Pathway in vitro and in vivo

“…Corilagin can protect against herpes simplex virus-1-induced encephalitis by reducing expression of TNF-α and NF-κB through inhibition of the TLR2 signaling pathway (13). Corilagin can suppress the interleukin-13/Janus kinase/signal transducer and activator of transcription-6 and microRNA-21/smad7/extracellular signal-regulated kinase signaling pathways in macrophages to reduce fibrosis severity (14). Corilagin has anti-oxidative and anti-inflammation function due to its suppression of expression of proinflammatory cytokines and mediators such as TNF-α, IL-6, inducible nitric oxide synthase, and cyclo-oxygenase-2 (15).…”