Abstract
Objective: Asthma is an inflammatory airway disease affecting most of the population in the world. The current medication for asthma relieves airway inflammation but it has serious adverse effects. Biochanin A (BCA), a phytoestrogen, is an active component present in red clover, alfalfa, soy having anti-oxidant and anti-inflammatory properties. BCA was identified as a natural activator of peroxisome proliferator-activated receptor-gamma (PPARγ).
Methods: The study aims to evaluate the effects of BCA in ovalbumin (OVA)-induced murine model of asthma and to study the role of PPARγ.
Results: We found that BCA administration reduced the severity of murine allergic asthma as evidenced histologically, and measurement of allergen-specific IgE levels in serum as well as in BAL fluid. BCA also reversed the elevated levels of inflammatory cytokines, cell infiltration, protein leakage into the airways and expression of hemoxygenase-1 in OVA-induced lungs. Further, we confirmed that BCA mediated inhibitory effects are mediated through PPARγ as assessed by treatment with PPARγ antagonist GW9662.
Conclusion: Our results suggest that BCA is efficacious in a preclinical model of asthma and may have the potential for the treatment of asthma in humans.
Keywords: Allergic airway disease, biochanin A, IgE, inflammation, isoflavones, PPARγ.
Graphical Abstract
[http://dx.doi.org/10.1146/annurev.immunol.17.1.255] [PMID: 10358759]
[http://dx.doi.org/10.1056/NEJM199010113231505] [PMID: 2215562]
[http://dx.doi.org/10.1016/j.rmed.2004.07.003] [PMID: 15715182]
[http://dx.doi.org/10.1517/14656560903200667] [PMID: 19678793]
[http://dx.doi.org/10.1056/NEJM199901213400306] [PMID: 9895400]
[http://dx.doi.org/10.1002/14651858.CD002178]
[http://dx.doi.org/10.1016/S0002-9343(99)80404-5] [PMID: 7847437]
[http://dx.doi.org/10.1016/j.rmed.2005.11.020] [PMID: 16412623]
[http://dx.doi.org/10.1517/13543776.13.4.489]
[http://dx.doi.org/10.1016/0305-1978(81)90030-2]
[http://dx.doi.org/10.1016/j.foodchem.2008.10.026]
[http://dx.doi.org/10.1007/s00436-008-1193-z] [PMID: 18810492]
[http://dx.doi.org/10.1016/j.tifs.2018.07.001]
[http://dx.doi.org/10.1016/j.etap.2015.04.020] [PMID: 25997126]
[http://dx.doi.org/10.3346/jkms.1991.6.4.325] [PMID: 1844641]
[http://dx.doi.org/10.1155/2011/635058]]
[http://dx.doi.org/10.31024/ajpp.2018.4.1.1]
[http://dx.doi.org/10.3389/fphar.2019.00793] [PMID: 31354500]
[http://dx.doi.org/10.1021/jf802298w] [PMID: 19053389]
[http://dx.doi.org/10.4049/jimmunol.164.3.1364] [PMID: 10640751]
[http://dx.doi.org/10.1164/rccm.200207-740OC] [PMID: 14563653]
[http://dx.doi.org/10.1002/1529-0131(200103)44:3<595:AID-ANR108>3.0.CO;2-8] [PMID: 11263774]
[http://dx.doi.org/10.1136/thorax.58.9.778] [PMID: 12947137]
[http://dx.doi.org/10.1161/01.HYP.0000085332.69777.D1]]
[http://dx.doi.org/10.1016/j.pupt.2005.02.005] [PMID: 16286236]
[http://dx.doi.org/10.1186/1465-9921-8-90] [PMID: 18053220]
[http://dx.doi.org/10.1016/j.jaci.2004.02.036] [PMID: 15131570]
[http://dx.doi.org/10.1136/thx.53.8.668] [PMID: 9828853]
[http://dx.doi.org/10.1046/j.1365-2222.2001.01179.x] [PMID: 11591199]
[PMID: 7723286]
[http://dx.doi.org/10.3109/10715769009148577] [PMID: 2189794]
[http://dx.doi.org/10.1016/j.bbrc.2015.05.104] [PMID: 26067554]
[http://dx.doi.org/10.1152/ajplung.00365.2017] [PMID: 29388469]
[http://dx.doi.org/10.1016/j.intimp.2019.04.001] [PMID: 30981081]
[PMID: 14907713]
[http://dx.doi.org/10.1016/j.ejphar.2011.01.024] [PMID: 21277298]
[http://dx.doi.org/10.1016/j.bcp.2014.07.018] [PMID: 25083916]
[http://dx.doi.org/10.1038/nri3632] [PMID: 24625841]
[http://dx.doi.org/10.1164/ajrccm.164.supplement_1.2103024]
[http://dx.doi.org/10.4049/jimmunol.1300730]]
[http://dx.doi.org/10.4049/jimmunol.170.5.2663] [PMID: 12594295]
[http://dx.doi.org/10.1007/s11064-014-1480-2] [PMID: 25432463]
[http://dx.doi.org/10.1042/CS20080195]]
[http://dx.doi.org/10.1164/ajrccm.164.8.2101070] [PMID: 11704601]
[http://dx.doi.org/10.1016/j.abb.2003.08.006] [PMID: 14522590]
[http://dx.doi.org/10.1155/2017/1069718] [PMID: 28656106]
[http://dx.doi.org/10.1084/jem.20021384] [PMID: 12900517]
[http://dx.doi.org/10.1016/S0140-6736(94)90931-8] [PMID: 7904001]
[http://dx.doi.org/10.1016/0891-5849(90)90034-G] [PMID: 2272532]
[http://dx.doi.org/10.1042/bj2790891] [PMID: 1835380]
[http://dx.doi.org/10.1155/2011/725926]
[http://dx.doi.org/10.3109/02770903.2015.1008138] [PMID: 26133060]
[http://dx.doi.org/10.1007/s00011-009-0037-3]]
[http://dx.doi.org/10.4049/jimmunol.1800649]]
[http://dx.doi.org/10.1016/S1081-1206(10)61173-8] [PMID: 16312170]
[http://dx.doi.org/10.1038/labinvest.3700456] [PMID: 16865089]
[http://dx.doi.org/10.1038/nature03988] [PMID: 16127449]
[http://dx.doi.org/10.1124/mol.105.017160] [PMID: 16150927]
[http://dx.doi.org/10.1016/j.micpath.2019.103846] [PMID: 31698051]
[http://dx.doi.org/10.1146/annurev.iy.12.040194.001041] [PMID: 8011280]
[http://dx.doi.org/10.3892/mmr.2011.599] [PMID: 21946955]
[http://dx.doi.org/10.1164/ajrccm.160.5.9806170] [PMID: 10556116]
[http://dx.doi.org/10.1164/rccm.200404-440OC] [PMID: 15215154]