Inhibitory effects of black tea theaflavin derivatives on 12‐O‐tetradecanoylphorbol‐13‐acetate‐induced inflammation and arachidonic acid metabolism in mouse ears

Abstract

Tea has been shown to possess several health beneficial properties primarily due to its polyphenolic content. The major polyphenolic compounds in black tea leaves are theaflavins (TFs) formed by oxidative coupling of catechins in tea leaves during its processing. In this paper, we report the characterization of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear inflammatory model and the inhibitory effects of major black tea TFs derivatives on this inflammation. In addition, the effect on inflammatory biomarkers, such as proinflammatory cytokines and arachidonic acid metabolites, are reported as well. A single topical application of TPA to ears of CD-1 mice induced a time- and dose-dependent increase in edema as well as formation of proinflammatory cytokine proteins interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in mouse ears. A single topical application of equimolar of black tea constituents (TF, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate) strongly inhibited TPA-induced edema of mouse ears. Application of TFs mixture to mouse ears 20 min prior to each TPA application once a day for 4 days inhibited TPA-induced persistent inflammation, as well as TPA-induced increase in IL-1beta and IL-6 protein levels. TFs also inhibited arachidonic acid (AA) metabolism via both cyclooxygenase (COX) and lipoxygenase pathways. This observation was substantiated by decreased amounts of AA metabolites prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. Combined application of TF and sulindac, a nonsteroidal anti-inflammatory drug resulted a significant synergetic anti-inflammatory effect. Oral administration of TFs or the hot water extract of black tea leaves also significantly inhibited TPA-induced edema in mouse ears. In conclusion, proinflammatory cytokines, IL-1beta and IL-6, as well as the intermediated metabolites of AA, PGE2, and LTB4 are good biomarkers for inflammation. Black tea constituents, TF and its derivatives, had strongly anti-inflammatory activity in vivo which may be due to their ability to inhibit AA metabolism via lipoxygenase and COX pathways.

Specific Dietary Polyphenols Attenuate Atherosclerosis in Apolipoprotein E–Knockout Mice by Alleviating Inflammation and Endothelial Dysfunction

“…44 Theaflavin protected against inflammation in mice by inhibiting arachidonic acid metabolism via both 5-lipoxygenase and cyclooxygenase pathways. 45 Sesamin inhibited lipopolysaccharide-induced interleukin 6 production by suppression of the p38 mitogen-activated protein kinase signal pathway and nuclear factor-B activation. 46 Our results showed that quercetin and theaflavin significantly inhibited the ex vivo production of proinflammatory LTB 4 in the vasculature of the ApoE Ϫ/Ϫ mice and were better inhibitors of vascular LTB 4 production than (Ϫ)-epicatechin and sesamin ( Figure 4C).…”

Trapping reactions of reactive carbonyl species with tea polyphenols in simulated physiological conditions

“…They cannot be isolated into pure compound under LH-20 chromatography. The composition ratio for TF2/TF29 was 3:1 after being quantified by the HPLC method [22].…”

Black tea polyphenol theaflavin suppresses LPS-induced ICAM-1 and VCAM-1 expression via blockage of NF-κB and JNK activation in intestinal epithelial cells

“…The theaflavins consist of theaflavin, theaflavin-3-gallate, theaflavin-3 0 -gallate and theaflavin-3,3 0 -gallate. Theaflavins have been suggested to reduce oxidative stress and inflammation in studies in vitro and in vivo [8][9][10][11][12][13][14]. However, although black tea is the most widely consumed beverage, the precise mechanisms by which black tea polyphenols exert these protective effects have not yet been as thoroughly elucidated as with green tea.…”