Metformin-like Methylglyoxal Scavengers from Macroalgae Chondrus crispus and Gracilaria vermiculophyla Preserve Cell Viability

A quantitative NMR assay was utilized to identify methylglyoxal-scavenging natural products from Rhodophytes, Chondrus crispus and Gracilaria vermiculophylla. This revealed the activity of guanylurea-containing amino acid derivatives, gongrine and gigartinine. The molecules share structural features with the frontline blood glucose-lowering drug and plant natural product derivative, metformin, and scavenge methylglyoxal via the same mechanism, resulting in an imidazole-containing Advanced Glycation Endproduct or AGE. The protective effect of the molecules reported here was evaluated in a cell-based model for reactive aldehyde stress using methylglyoxal exposure to reduce cell viability. Gongrine, gigartinine, and metformin all preserve cell viability in HepG2 following methylglyoxal exposure. This is the first report of methylglyoxal scavenging and cell viability protection of these macroalgae-derived guanylurea-containing natural products, which can be found in high abundance in commonly consumed and industrially produced macroalgae species. The compounds presented here, along with their algal sources, offer a unique opportunity to produce guanylureas with therapeutic potential through sustainable production methods from easily cultivated algal sources.