(−)-Epigallocatechin-3-gallate inhibits human angiotensin-converting enzyme activity through an autoxidation-dependent mechanism

Abstract

We investigated the molecular mechanisms involved in the angiotensin-converting enzyme (ACE) inhibition by (-)-epigallocatechin-3-gallate (EGCg), a major tea catechin. EGCg inhibited both the ACE activity in the lysate of human colorectal cancer cells and human recombinant ACE (rh-ACE) in a dose-dependent manner. Co-incubation with zinc sulfate showed no influence on the rh-ACE inhibition by EGCg, whereas it completely counteracted the inhibitory effect of ethylenediaminetetraacetic acid, a chelating-type ACE inhibitor. Although hydrogen peroxide was produced by the autoxidation of EGCg, hydrogen peroxide itself had little effect on the ACE activity. Conversely, the co-incubation of EGCg with borate or ascorbic acid significantly diminished the EGCg inhibition. A redox-cycling staining experiment revealed that rh-ACE was covalently modified by EGCg. A Lineweaver-Burk plot analysis indicated that EGCg inhibited the ACE activity in a non-competitive manner. These results suggested that EGCg might allosterically inhibit the ACE activity through oxidative conversion into an electrophilic quinone.

Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments

“…A mechanism for the autoxidation of EGCG was based on the formation of EGCG quinone, EGCG dimer quinone, and other related compounds [ 70 ]. For example, EGCG can inhibit the angiotensin-converting enzyme (ACE) activity through oxidation into an electrophilic quinone [ 71 ], which may be related to the treatment of cardiovascular diseases. Moreover, the formation of autoxidized products also contributes to the inhibition of fibrillation [ 72 ].…”

In silico Nigellidine (N. sativa) bind to viral spike/active-sites of ACE1/2, AT1/2 to prevent COVID-19 induced vaso-tumult/vascular-damage/comorbidity

“…2 ; supplementary file, S-table1). This binding was compared with some known/reported binder epigallocatechin-3-gallate(EGCG) [ 19 ]; −4.53 kcal/mol with ki 479.87 μmol and Theaflavin gallate [TFDG]; −2.85 kcal/mol with ki value 8.2 μmol. Best ten binding values of nigellidine, EGCG and TFDG to ACE2 are presented in supplementary file, S-table2.…”

Covalent adduction of endogenous and food-derived quinones to a protein: its biological significance

“…Meanwhile, a study revealed that EGCg inhibited angiotensin-converting enzyme (ACE) activity through oxidative conversion into quinone and successive covalent binding of the quinone to ACE. ( 11 ) Furthermore, the paper revealed that EGCg is a non-competitive inhibitor of ACE and EGCg binds to a specific site but not the active site of ACE.…”

“…( 9 , 10 , 18 ) Tea has beneficial effects on human health and it has been speculated that these effects are caused by the components in tea. The quinone of EGCg could participate in some of the biological activities of tea; ( 11 ) we discuss the mechanisms behind this in section 3 below. Flavonoid-derived quinones, such as quercetin quinone, might be key players in the induction of cell protection against oxidative stress.…”

“…( 7 ) Moreover, even after the ingestion of food-derived polyphenols (catechols), quinones can form endogenously in the gut or in organs/tissues. ( 8 – 11 ) Some vitamins and related compounds also have or develop a quinone moiety. For example, vitamin K has a quinone moiety in its standard form, while tocopherol (vitamin E) forms tocopherol quinone through antioxidative action.…”