Anti-inflammatory properties of pterocarpanquinone LQB-118 in mice

作者：Rica Ingred G^*; Netto Chaquip D; Renno Magdalena N; Abreu Paula A; Costa Paulo R R; da Silva Alcides J M; Cavalcante Moises C M

来源：Bioorganic & Medicinal Chemistry, 2016, 24(18): 4415-4423.

DOI：10.1016/j.bmc.2016.07.046

• Inflammation
• Pterocarpanquinone
• LQB 118
• TNF-alpha
• Estrogen receptors

Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic properties and also shows great inhibitory effect on TNF-alpha release in vitro. Here, its anti-inflammatory activity was evaluated in a lipopolysaccharide (LPS)-induced lung inflammation model in C57BL/6 mice. LPS inhalation induced a marked neutrophil infiltration to the lungs which was reduced by intraperitoneal treatment with (+/-)-LQB-118 in a similar manner to that of dexamethasone and even better than that of acetylsalicylic acid. Moreover, (+/-)-LQB-118 administration resulted in decrease of NF-kappa B activation and KC level in lungs, with a pronounced inhibitory effect on TNF-alpha release, measured in bronchoalveolar lavage fluid. Trying to understand the anti-inflammatory mechanism by which (+/-)-LQB-118 acts, we performed a molecular modeling analysis, including docking to estrogen receptors alpha and beta. Results suggested that (+/-)-LQB-118 may bind to both receptors, with a similar orientation to 17-beta-estradiol. Together, these results showed that (+/-)-LQB-118 exhibits an anti-inflammatory effect, most likely by inhibiting TNF-alpha release and NF-kappa B activation, which may be related to the estrogen receptor binding.

• 出版日期2016-9-15