Epigallocatechin gallate is a potent inhibitor of cystathionine beta-synthase: Structure-activity relationship and mechanism of action

Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies

“…In the past, many polyphenolic compounds similar to EGCG were selected in the screening of CBS inhibitors, but most of them were not as effective as the most commonly used AOAA for inhibition. In contrast, EGCG inhibits CBS-catalyzed H 2 S production at sub-micromolar concentrations (IC 50 : 0.12 μM) and has been shown to significantly inhibit H 2 S production in CRC or Down syndrome cell models in vitro [ 162 ]. Remarkably, unlike AOAA and its derivatives or hydrazine CBS inhibitors, the inhibition of CBS by EGCG does not target PLP or response mechanisms, but exploits certain structural or conformational features unique to CBS, which makes it a CBS-specific inhibitor.…”

“…Remarkably, unlike AOAA and its derivatives or hydrazine CBS inhibitors, the inhibition of CBS by EGCG does not target PLP or response mechanisms, but exploits certain structural or conformational features unique to CBS, which makes it a CBS-specific inhibitor. In addition, it has been proposed that EGCG can oxidize H 2 S produced by CBS to form polysulfides [ 161 ], indicating that EGCG may act as a scavenger of H 2 S. Nonetheless, a study by Szabo's group discovered that EGCG exhibited some H 2 S scavenging activity only at higher concentrations and also inhibited non–H 2 S–generating HsCBS, indicating that it is a true CBS inhibitor [ 162 ]. Although EGCG and other polyphenolic bioflavonoids usually have a variety of pharmacological targets and actions, their therapeutic effects on CRC may not be attributed to CBS inhibition alone.…”

State‐of‐the‐art therapy for Down syndrome

“…15 Recently, it was also proven to be safe in children with Down syndrome. 71 Interestingly, not only does epigallocatechin-3-gallate inhibit DYRK1A, but it also targets key postsynaptic and plasticity-related pathways 72,73 and inhibits CBS, 74 a major H 2 S-generating enzyme, potentially contributing to ameliorating cognition in Down syndrome. 75 However, given that DYRK1A function is dosage dependent, an excessive long-term inhibition may be deleterious, especially during development.…”

Epigenetic Control of Hyperuricemia and Gout by Gene Writer DNMT1 and RNA Editor ADAR1: Mechanism of Gout and Amyloid Dissolution in Down Syndrome

“…Furthermore, in clinical trials folic acid (FA) supplementation in DS have been tried but the study did not show a protective effect of FA on heart anomalies among infants with DS (31,32). In this context, we opine that innovative approaches such as CBS inhibitors may offer new avenues for mitigating H 2 S levels and addressing mitochondrial dysfunction in DS subjects (18,33). Additionally, the potential role(s) of 3MST and pyruvate acetyl-CoA in epigenetic gene regulation in DS represent novel areas of research (34).…”