The SAM-m6A axis as an unexplored therapeutic hub for plant-derived regulation of disease metabolism

Zhao, Yuxuan and Liang, Jingyimei and Ma, Wanning and Xiao, Jianbo and Cao, Hui UNSPECIFIED (2026) The SAM-m6A axis as an unexplored therapeutic hub for plant-derived regulation of disease metabolism. Pharmacological Research, 225. p. 108114. ISSN 10436618

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Abstract

S-adenosylmethionine (SAM) is the main cellular methyl donor and a core product of one-carbon metabolism. Its balance with S-adenosylhomocysteine (SAH) defines methylation potential and shapes epigenetic and epitranscriptomic outputs. RNA N6-methyladenosine (m6A) directly depends on SAM and is controlled by a writer-reader-eraser system. This review summarizes how altered SAM supply, SAH accumulation, and shifts in the SAM/SAH ratio can reprogram m6A landscapes. These changes can occur in cancer, metabolic disease, inflammation, and neurodegeneration. We integrate metabolic control of SAM generation and consumption with regulation of METTL3/METTL14, WTAP and related cofactors, and the erasers FTO and ALKBH5. We also assess plant-derived bioactive compounds proposed to act on this coupling. Most phytochemicals do not behave as potent, selective m6A enzyme inhibitors. They more often act upstream by reshaping one-carbon metabolism, redox state, and protein expression. This profile contrasts with canonical synthetic inhibitors that block a single node with higher affinity and more predictable pharmacodynamics. Together, the evidence supports the SAM-m6A axis as a practical framework to connect nutrient state with RNA fate decisions. It also highlights key gaps for translation, including target engagement, dose-exposure alignment, and causal validation of m6A-dependent phenotypes.

Item Type:	Article
Uncontrolled Keywords:	S-Adenosylmethionine N6-Methyladenosine Plant-derived bioactive compounds Tea Polyphenols Disease
Subjects:	Subjects > Biomedicine
Divisions:	Europe University of Atlantic > Research > Scientific Production
Depositing User:	Sr Bibliotecario
Date Deposited:	04 Feb 2026 10:06
Last Modified:	04 Feb 2026 10:06
URI:	http://repositorio.funiber.org/id/eprint/27157

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