peoniflorin and Granuloma

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.

Topics: Animals; Arginase; Benzoates; Bridged-Ring Compounds; Female; Gene Expression; Glucosides; Granuloma; Humans; Hyaluronic Acid; Interleukin-13; Janus Kinase 2; Kupffer Cells; Liver; Liver Cirrhosis; Macrophage Activation; Macrophages; Mice; Mice, Inbred BALB C; Monoterpenes; Nitric Oxide Synthase Type II; Phosphorylation; Schistosoma japonicum; Schistosomiasis japonica; STAT6 Transcription Factor

Treatment of liver fibrosis associated with Schistosoma japonicum ova-induced granulomas remains a challenging proposition. Paeoniflorin (PAE, C23H28O11) has anti-inflammatory, anti-allergic, and immunoregulatory effects and it is commonly used in Chinese Herbal prescriptions to treat hepatic disorders. The present study was carried out to investigate the effects of PAE on hepatic fibrosis of mice infected with S. japonicum and to explore its possible mechanism. Upon pathological examination of PAE-treated mice, the size of egg granuloma, fibrosis scores, the concentration of IL-13 and hydroxyproline in liver were significantly reduced compared with the model mice. In the primary culture of hepatic stellate cells (HSCs), PAE inhibited IL-13-induced collagen synthesis. These results suggested that PAE might alleviate the hepatic granulomas and fibrosis caused by S. japonicum and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to decrease the level of IL-13 and to interfere with the IL-13 signalling molecule in HSCs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Bridged-Ring Compounds; Cells, Cultured; Collagen; Female; Gene Expression Regulation; Glucosides; Granuloma; Hepatic Stellate Cells; Interleukin-13; Liver Cirrhosis; Mice; Mice, Inbred BALB C; Monoterpenes; Paeonia; Schistosoma japonicum; Schistosomiasis japonica; Signal Transduction

The pharmacological properties of the five samples of glycyrrhizic acid, paeoniflorin, the extracts of Glycyrrhizae Radix, the extracts of Paeoniae Radix and a preparation of Chinese drug Shakuyakukanzo-To were compared by investigating their actions in the carrageenan-induced paw edema, the cotton pellet granuloma formation and acetic acid-induced writhing syndrome tests, using ddY-strain mice. The concentrations of glycyrrhizic acid and paeniflorin, the main components of Glycyrrhizae Radix and Paeoniae Radix respectively, were determined in the preparations by high performance liquid chromatography. Anti-inflammatory activity was observed with the doses of glycyrrhizic acid, 3.0 and 30.0 mg/kg p.o., which are almost equivalent to the quantities contained in the extracts of Glycyrrhizae Radix, 18.0 (normal human dose per day) and 180.0 mg/kg, or in Shakuyakukanzo-To, 32.0 (normal human dose per day) and 320.0 mg/kg, respectively and with the doses of the extracts of Glycyrrhizae Radix, 18.0 and 180.0 mg/kg p.o., but not with the doses of Shakuyakukanzo-To, 32.0 and 320.0 mg/kg p.o., in carrageenan-induced edema and cotton pellet method. Doses of paeoniflorin (2.0, 20.0 and 200.0 mg/kg p.o.) and the extracts of Paeoniae Radix, 21.0 (normal human dose per day) and 210.0 mg/kg p.o., which contain almost equivalent quantities of paeoniflorin, 2.0 and 20.0 mg/kg, respectively, showed significant inhibitory effects in the writhing syndrome test. Furthermore, Shakuyakukanzo-To, 32.0 and 320.0 mg/kg p.o., which contain almost equivalent quantities of paeoniflorin, 2.0 and 20.0 mg/kg, showed strong effects in this test.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetates; Acetic Acid; Animals; Anti-Inflammatory Agents; Benzoates; Bridged-Ring Compounds; Carrageenan; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Edema; Glucosides; Glycyrrhetinic Acid; Glycyrrhiza; Glycyrrhizic Acid; Granuloma; Male; Mice; Monoterpenes; Paeonia; Pain; Plant Extracts; Plants, Medicinal