5-(3′,4′-Dihydroxyphenyl-γ-valerolactone), a Major Microbial Metabolite of Proanthocyanidin, Attenuates THP-1 Monocyte-Endothelial Adhesion

Abstract

Several metabolomics of polymeric flavan-3-ols have reported that proanthocyanidins are extensively metabolized by gut microbiota. 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone (DHPV) has been reported to be the major microbial metabolite of proanthocyanidins. We demonstrated that DHPV has stronger prevention effect on tumor necrosis factor (TNF)-α-stimulated adhesion of THP-1 human monocytic cells to human umbilical vein endothelial cells compared to its potential precursors such as procyanidin A1, A2, B1 and B2, (+)catechin, (−)epicatechin and its microbial metabolites such as 3-(3,4-dihydroxyphenyl)propionic acid and 2-(3,4-dihydroxyphenyl)acetic acid. Mechanism study showed that DHPV prevents THP-1 monocyte-endothelial cell adhesion by downregulating TNF-α-stimulated expressions of the two biomarkers of atherosclerosis such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1, activation of nuclear factor kappa B transcription and phosphorylation of I kappa-B kinase and IκBα. We suggested that DHPV has higher potentiality in prevention of atherosclerosis among the proanthocyanidin metabolites.

Colonic metabolites from flavanols stimulate nitric oxide production in human endothelial cells and protect against oxidative stress-induced toxicity and endothelial dysfunction

“…In particular, small phenolic acids derivatives from anthocyanins were able to induce heme oxygenase-1 (HO-1) and modulate eNOS activity, resulting in reduced superoxide production and improved NO bioavailability in human umbilical vein endothelial cells (Edwards et al, 2015). More recently, Lee et al (Lee et al, 2017) have demonstrated that a major microbial metabolite of proanthocyanidin (5-dihydroxyphenylvalerolactone) attenuated THP-1 monocyte-endothelial adhesion in human umbilical vein endothelial cells. Taken together, these findings clearly confirmed that 1) microbial phenolic metabolites may independently have bioactivity improving vascular function and 2) this effect may be definitely crucial since they are probably the main active compounds in vivo.…”

Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

“…The cell adhesion assay was conducted as previously described with modification (Lee et al, ). Briefly, THP‐1 cells were labeled with 2 μM of the fluorescent probe Calcein AM (Solarbio, Beijing, China) in RPMI‐1640 medium at 37°C for 30 min in the dark.…”

Rethinking the Mechanism of the Health Benefits of Proanthocyanidins: Absorption, Metabolism, and Interaction with Gut Microbiota

“…Studies have shown that metabolites of proanthocyanidins also exhibited strong bioactivity. 5‐(3′,4′‐dihydroxyphenyl)‐γ‐valerolactone, a metabolite of proanthocyanidins, inhibit the adhesive activity of uropathogenic Escherichia coli in bladder epithelial cells and thus attenuated THP‐1 monocyte‐endothelial adhesion (Lee et al., ; Mena et al., ). Also, dihydroxyphenyl‐γ‐valerolactone derivatives which are metabolites of cranberry proanthocyanidins have been proved to prevent invasion of UPEC ATCC R 53503 TM which may cause UTIs, while 5‐(3’‐hydroxyphenyl)‐γ‐valerolactone‐4‐ O ‐sulphate also shows neuroprotective effects at 50 µM (Mena et al., ).…”