title: Paeoniflorin attenuates schistosomiasis japonica-associated liver fibrosis through inhibiting alternative activation of macrophages.
abstract: Interleukin (IL)-13 and alternatively activated macrophages (AAMs) play an important role in liver granuloma and fibrosis of schistosomiasis. Paeoniflorin (PAE, C23H28O11) has been reported to have an anti-hepatic fibrosis effect in schistosomiasis; however, the mechanism has not been fully elucidated. In this study, we measured serum hyaluronic acid (HA) concentrations, liver granuloma diameter and volume density, fibrosis degree and expressions of IL-13, arginase-1 (ARG-1), nitric oxide synthase-2 (NOS-2), and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in mice liver of schistosomiasis. Then we detected expressions of specific biomarkers of AAMs and activity of Arg-1 in Kupffer cells (KCs) from infected and PAE-treated mice, or in KCs from uninfected mice, but exposed to rIL-13 in vitro. Finally, we observed expression of IL-13 signalling molecules in KCs and secretion of IL-13 from lymphocytes of infected and PAE-treated mice. Our results showed that during schistosomiasis, IL-13 expression and secretion increased with liver macrophages activated alternatively. PAE not only directly inhibited alternative activation of macrophages via reducing the phosphorylations of janus-activated kinase 2 (JAK2) and/or STAT6, leading to reduction of AAMs-related markers and Arg-1 activity, but also indirectly suppressed alternative activation of macrophages through decreasing secretion of IL-13. PAE might be a promising prophylactic agent for hepatic granuloma and fibrosis of schistosomiasis japonica.
authors.affiliation: Department of Microbiology and Parasitology, Anhui Key Laboratory of Microbiology and Parasitology, Anhui Medical University, Hefei, China.
authors.forename: Deyong
authors.initials: D
authors.lastname: Chu
authors.forename: Mingzhan
authors.initials: M
authors.lastname: Du
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Hu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001565:Benzoates / Q000008:administration & dosage* / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D005960:Glucosides / Q000008:administration & dosage* / Q000627:therapeutic use; D006099:Granuloma / Q000209:etiology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012549:Schistosoma japonicum / Q000502:physiology*; D012554:Schistosomiasis japonica / Q000150:complications / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control; D006027:Glycosides
chemical_list: D001119:Arginase; D001565:Benzoates; D001952:Bridged-Ring Compounds; D005960:Glucosides; D006820:Hyaluronic Acid; D018793:Interleukin-13; D053614:Janus Kinase 2; D039821:Monoterpenes; D052247:Nitric Oxide Synthase Type II; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C015423:peoniflorin; D006027:Glycosides; C496317:Nos2 protein, mouse; C507926:Jak2 protein, mouse; C544448:Arg1 protein, mouse