Malaysian Tualang Honey Inhibits Hydrogen Peroxide-Induced Endothelial Hyperpermeability

<jats:p>Malaysian Tualang honey (TH) is a known therapeutic honey extracted from the honeycombs of the Tualang tree (Koompassia excelsa) and has been reported for its antioxidant, anti-inflammatory, antiproliferative, and wound healing properties. However, the possible vascular protective effect of TH against oxidative stress remains unclear. In this study, the effects of TH on hydrogen peroxide- (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-) elicited vascular hyperpermeability in human umbilical vein endothelial cells (HUVECs) and Balb/c mice were evaluated. Our data showed that TH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to HUVECs. Induction with 0.5 mM H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> was found to increase HUVEC permeability, but the effect was significantly reversed attenuated by TH (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>), of which the permeability with the highest inhibition peaked at 0.1%. In Balb/c mice, TH (0.5 g/kg-1.5 g/kg) significantly (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>) reduced H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> (0.3%)-induced albumin-bound Evans blue leak, in a dose-dependent manner. Immunofluorescence staining confirmed that TH reduced actin stress fiber formation while increasing cortical actin formation and colocalization of caveolin-1 and <jats:italic>β</jats:italic>-catenin in HUVECs. Signaling studies showed that HUVECs pretreated with TH significantly (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>) decreased intracellular calcium release, while sustaining the level of cAMP when challenged with H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>. These results suggested that TH could inhibit H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-induced vascular hyperpermeability in vitro and in vivo by suppression of adherence junction protein redistribution via calcium and cAMP, which could have a therapeutic potential for diseases related to the increase of both oxidant and vascular permeability.</jats:p>