Novel l‑Cysteine Incomplete Degradation Method for Preparation of Procyanidin B2-3′‑O‑Gallate and Exploration of its in Vitro Anti-inflammatory Activity and in Vivo Tissue Distribution

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3′-O-gallate (B2-3′-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure–activity relationship of B2-3′-G was further evaluated in vitro through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. The results suggested that the better protective effects of B2-3′-G against inflammation were attributed to its polymerization degree and the introduction of the galloyl group, compared to its four corresponding structural units. In vivo experiments demonstrated that the B2-3′-G prototype was distributed in plasma, small intestine, liver, lung, and brain. Remarkably, B2-3′-G was able to penetrate the blood–brain barrier and appeared to play an important role in improving brain health. Furthermore, a total of 18 metabolites were identified in tissues. Potential metabolic pathways, including reduction, methylation, hydration, desaturation, glucuronide conjugation, and sulfation, were suggested.