Abstract:
Alcoholic liver disease (ALD) is a significant public health problem worldwide. Numerous natural molecules, including curcumin, have been extensively studied as potential treatment agents for ALD. Tetrahydrocurcumin (THC), the reductive metabolite of curcumin, was previously reported to exert the potent antioxidant activity against chemical-induced oxidative stress suggesting the potential of THC to be used as a protective agent for ALD. However, THC has poor water solubility limiting its pharmacological activity. In the present study, tetrahydrocurcumin-diglutaric acid (TDG) was synthesized. The solubility of TDG at pH 6.8 was higher than THC approximately 20 times with a logP value of 3.03. TDG was stable in acidic solution, but it was not stable in basic conditions and plasma. TDG was completely degraded within 4 h in plasma with a rate constant of 0.758 h-1 and half-life 0.9 h. The protective effect of THC and TDG against alcohol-induced hepatotoxicity was evaluated by using the HepG2 cell line as an in vitro model. The results show that the pre-treated cells with TDG exhibited a more effective protective effect than THC by reducing ROS levels and restoring the antioxidant system. Moreover, THC and TDG can suppress the apoptosis pathway via modulating the activation of caspases. These results indicated that TDG could be a potential therapeutic agent for ALD with a higher protective effect than THC.
