Anti-allergic effects of PG102, a water-soluble extract prepared from Actinidia arguta, in a murine ovalbumin-induced asthma model

Background Asthma is a chronic inflammatory disease of the lung and its incidence has been increasing around the world. We previously reported that oral administration of a water-soluble extract prepared from Actinidia arguta, code-named PG102, could modulate the level of Th1 and Th2 cytokines and suppress the production of immunoglobulin E (IgE) in the ovalbumin (OVA)-immunized murine model as well as in the in vitro cell culture system, and furthermore could significantly improve dermatitis conditions in the NC/Nga murine model. These data suggested that PG102 might have therapeutic effects in a broad range of allergic diseases. Objective To assess the possible anti-allergic effects of PG102 in the OVA-induced murine asthma model. Methods The quality of PG102 was standardized, using its effects on the production of IgE, IL-5, and IL-13, in in vitro cell culture systems. To test effects on asthma, BALB/c mice were orally administrated with PG102, followed by OVA sensitization and challenge to induce asthmatic symptoms. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid, serum, and lung tissue were analysed by using various methods. Results PG102 could decrease the level of IgE, IL-5, and IL-13 in in vitro cell culture systems with IC(50) being 1.12-1.43 mg/mL. PG102 could ameliorate asthmatic symptoms, including AHR and eosinophilia in the lungs. Such improvement of asthmatic symptoms by PG102 was accompanied by the down-regulation of IL-5 and IgE. In PG102-treated mice, high level expression of heme oxygenase-1, a potent anti-inflammatory enzyme, was observed in alveolar inflammatory cells, while the mRNA levels of foxp3, TGF-beta 1, and IL-10, important markers for regulatory T cells, were also up-regulated in the lung tissue. Conclusions PG102 may have potential as a safe and effective reagent for the prevention or treatment of asthma.Kim DH, 2008, J IMMUNOL, V180, P2062Arnold E, 2008, COCHRANE DB SYST REV, DOI 10.1002/14651858.CD005989.pub2Xia ZW, 2007, AM J PATHOL, V171, P1904, DOI 10.2353/ajpath.2007.070096Longui CA, 2007, J PEDIAT, V83, pS163, DOI 10.2223/JPED.1713Bloemen K, 2007, IMMUNOL LETT, V113, P6, DOI 10.1016/j.imlet.2007.07.010Hendeles L, 2007, ANN PHARMACOTHER, V41, P1397, DOI 10.1345/aph.1K005Park EJ, 2007, J INVEST DERMATOL, V127, P1154, DOI 10.1038/sj.jid.5700658Lee JH, 2007, CLIN CANCER RES, V13, P2584, DOI 10.1158/1078-0432.CCR-06-1785Bousquet J, 2007, ALLERGY, V62, P102, DOI 10.1111/j.1398-9995.2006.01305.xXia ZW, 2006, J IMMUNOL, V177, P5936BRAMAN SS, 2006, CHEST S1, V130, P4Park EJ, 2005, J ALLERGY CLIN IMMUN, V116, P1151, DOI 10.1016/j.jaci.2005.07.024Lee K, 2005, GLIA, V51, P1, DOI 10.1002/glia.20179Keshavan P, 2005, J IMMUNOL, V174, P3709Almolki A, 2004, AM J PHYSIOL-LUNG C, V287, pL26, DOI 10.1152/ajplung.00237.2003Masoli M, 2004, ALLERGY, V59, P469Zheng SG, 2004, J IMMUNOL, V172, P5213Cho JY, 2004, J CLIN INVEST, V113, P551, DOI 10.1172/JCI200419133Nakamura K, 2004, J IMMUNOL, V172, P834Ameredes BT, 2003, AM J PHYSIOL-LUNG C, V285, pL1270, DOI 10.1152/ajplung.00145.2003Fontenot JD, 2003, NAT IMMUNOL, V4, P330, DOI 10.1038/ni904Hori S, 2003, SCIENCE, V299, P1057, DOI 10.1126/science.1079490Baranano DE, 2002, P NATL ACAD SCI USA, V99, P16093, DOI 10.1073/pnas.252626999Chung Y, 2002, IMMUNOBIOLOGY, V206, P408Blanc PD, 2001, CHEST, V120, P1461Chapman JT, 2001, AM J PHYSIOL-LUNG C, V281, pL209Busse WW, 2001, NEW ENGL J MED, V344, P350Holt PG, 2000, AM J RESP CRIT CARE, V162, pS151Chang TW, 2000, NAT BIOTECHNOL, V18, P157Hamelmann E, 1999, ALLERGY, V54, P297Martell M, 1999, J CLIN MICROBIOL, V37, P327Wills-Karp M, 1999, ANNU REV IMMUNOL, V17, P255Chong BTY, 1998, J PHARMACOL TOXICOL, V39, P163Hamelmann E, 1997, AM J RESP CRIT CARE, V156, P766Lemanske RF, 1997, AM J RESP CRIT CARE, V156, P685Worm M, 1997, J MOL MED-JMM, V75, P440LOETSCHER P, 1994, FASEB J, V8, P1055HIRANO T, 1989, J IMMUNOL METHODS, V119, P145STOCKER R, 1987, SCIENCE, V235, P1043TENHUNEN R, 1969, J BIOL CHEM, V244, P6388