Synthesis, physicochemical properties, and protective effects of a novel water-soluble tetrahydrocurcumin-diglutaric acid prodrug on ethanol-induced toxicity in HepG2 cells

A Stability-Indicating Assay for Tetrahydrocurcumin-Diglutaric Acid and Its Applications to Evaluate Bioaccessibility in an In Vitro Digestive Model

“…Similarly, TDG and THC can exhibit keto-enol tautomerism as curcumin. However, the keto tautomer is usually slightly presented in the 1 H and 13 C NMR studies as previously reported [ 21 ]. Under the chromatographic condition used in this study, the keto-enol tautomerization of analytes is noticeable even though the acidic and polar mobile phase was used ( Figure 2 A).…”

“…In this regard, our developed UHPLC-UV method also provides the benefit of separating and providing a deep insight into the tautomer characteristics of THC and its derivatives. More importantly, the developed method is used not only for qualifying TDG in bulk drugs and its formulation but has also been applied in verifying in vitro kinetic [ 21 ] and bioaccessibility studies of TDG compared to THC.…”

“…The greater amount of TDG in the simulated gastrointestinal fluids indicated that TDG was more available than THC for absorption ( Figure 4 D). The solubility profile of TDG, especially in essential solutions, may contribute to an improved bioaccessibility of TDG [ 21 ]. Moreover, THC and TDG were stable after incubation in the SIF at 37 °C for 2 h. The development of drug candidates with better aqueous solubility is a dominant strategy to improve bioaccessibility, which may enhance drug bioavailability, resulting in greater pharmacological activities.…”

“…They found that mucoadhesive properties, in combination with the aqueous solubility enhancement, contributed to the increased bioaccessibility [ 20 ]. We recently synthesized tetrahydrocurcumin-diglutaric acid (TDG, Figure 1 B) with enhanced hepatoprotective effects against alcohol-induced liver toxicity compared to THC [ 21 ], suggesting its potential use for the treatment of alcoholic liver disease (ALD) [ 21 ]. Structurally, as a diglutaric ester prodrug of THC, TDG was converted to its parent THC and subsequently exerted hepatoprotective effects.…”

“…Later, HPLC coupled with mass spectrometry (MS) [ 22 , 24 , 25 ] was developed. During the quantification method development of TDG for solubility, partition coefficient and kinetic studies [ 21 ], a simple analytical method for the simultaneous determination of TDG and THC in aqueous solutions and plasma was achieved. Nevertheless, this method has not been validated and proven to be a stability-indicating assay (SIA) for future implementation as a routine quantification of TDG in raw materials and other metrics.…”