Oral green tea catechin metabolites are incorporated into human skin and protect against UVR-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-HETE

1 Green tea catechins (GTC) reduce ultraviolet radiation (UVR)-induced inflammation in 2 experimental models but human studies are scarce, and their cutaneous bioavailability and 3 mechanism of photoprotection are unknown. We aimed to examine oral GTC cutaneous 4 uptake, ability to protect human skin against erythema induced by a UVR dose-range, and 5 impact on potent cyclooxygenase and lipoxygenase-produced mediators of UVR6 inflammation, prostaglandin (PG)E2 and 12-hydroxyeicosatetraenoic acid (HETE), 7 respectively. In an open oral intervention study, 16 healthy humans (phototype I/II) were 8 given low-dose GTC (540 mg) with vitamin C (50 mg) daily for 12 weeks. Preand post9 supplementation, buttock skin was exposed to UVR and resultant erythema quantified. Skin 10 blister fluid and biopsies were taken from unexposed and UVR-exposed skin 24h-post a pro11 inflammatory UVR challenge (3 minimal erythema doses). Urine, skin tissue and fluid were 12 analysed for catechin content, and skin fluid for PGE2 and 12-HETE, by liquid 13 chromatography coupled to tandem mass spectrometry. Fourteen completing subjects were 14 supplement-compliant (12F, median 42.5y, range 29-59y). Benzoic acid levels were 15 increased in skin fluid post-supplementation (P=0.03), and methylated gallic acid and several 16 intact catechins and hydroxyphenyl-valerolactones were detected in skin tissue and fluid. 17 Area-under-curve analysis for UVR-erythema revealed reduced response post-GTC 18 (P=0.037). Pre-supplementation, PGE2 and 12-HETE were UVR-induced (P=0.003, 19 P=0.0001). After GTC, UVR-induced 12-HETE reduced from mean±SD 64±42 to 41±32 20 pg/L (P=0.01) while PGE2 was unaltered. Thus GTC intake results in incorporation of 21 catechin metabolites in human skin associated with abrogated UVR-induced 12-HETE; this 22 may contribute to protection against sunburn inflammation and potentially longer-term UVR23 mediated damage. 24