Human Serum Albumin Increases the Stability of Green Tea Catechins in Aqueous Physiological Conditions

Abstract

Epicatechin (EC), epigallocatechin (EGC), epicatechingallate (ECG) and epigallocatechingallate (EGCG) are antioxidants present in the green tea, a widely used beverage whose health benefits are largely recognized. Nevertheless, major physicochemical limitations, such as the high instability of catechins, pose important questions concerning their potential pharmacological use. Recent studies indicate that binding of catechins with plasmatic proteins may modulate their plasma concentration, tissue delivery and biological activity. After 5 minutes of incubation with HSA both ECG and EGCG were fully bound to HSA, while after 48h incubation only 41% of EC and 70% of EGC resulted linked. HSA had a strong stabilizing effect on all catechins, which could be found in solution between 29 and 85% even after 48h of incubation. In the absence of HSA, EGC and EGCG disappeared in less than 24h, while ECG and EC were found after 48h at 5 and 50%, respectively. The stabilizing effect of HSA toward EGCG, obtained in aqueous physiological conditions, resulted stronger in comparison to cysteine and HCl, previously reported to stabilize this polyphenol. Because of the multitude of contradictory data concerning in vivo and in vitro antioxidant-based experimentations, we believe our work may shed some light on this debated field of research.

Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases

“…Catechins are generally most stable in solution at a pH range of 4-6. It is now known that human serum albumin acts as a stabilizer, binding to the catechins and then transporting them [ 50 ]. Various studies in humans have found that the peak concentrations of catechins and their metabolites occur in blood plasma between 1.5 and 2 hours after ingestion and in urine between 4 and 6 hours after ingestion.…”

Isocitrate dehydrogenase 1-mutated cancers are sensitive to the green tea polyphenol epigallocatechin-3-gallate

“…4b). Because EGCG binds to serum albumin [37], possibly diminishing cellular uptake, we repeated the LC-MS experiment, but now cultured cells in serum-free medium. Under these conditions, EGCG treatment resulted in a significant reduction of 13 C- flux from *Glu to D- 2-HG (Additional file 1: Figure S1).

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“…Anticancer effects of EGCG can be diminished due to oxidation of the compound [66], resulting in low circulating doses after oral administration [67, 68]. Furthermore, EGCG in the circulation is mostly albumin-associated, increasing stability but decreasing bioavailability [37]. Methods to increase bioavailability via nanomedicine and controlled delivery are currently being explored [69, 70].…”

The Intrinsic Virtues of EGCG, an Extremely Good Cell Guardian, on Prevention and Treatment of Diabesity Complications

“…In part, this is due to EGCG high solubility, which limits its absorption through membranes and in part to its chemical steadiness, that is elevated in an acidic environment such as the stomach during gastric digestion, but decreases rapidly in alkaline duodenal environments [ 81 ]. The wide distribution of EGCG in most tissues is explained by its avid binding to albumin, which stabilizes and transports EGCG in the bloodstream [ 82 ]. In humans, as in mice, EGCG undergoes similar phase II biotransformation processes that result in methylated, sulfated and glucuronidated products as the major EGCG metabolites [ 83 , 84 ].…”