Long-Term Effects of (–)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats

Abstract

Rheumatoid arthritis (RA)—a widespread chronic inflammatory disease in industrialized countries—is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the pharmacological mode of action of this polyphenol.

Could Polyphenols Help in the Control of Rheumatoid Arthritis?

“…Morinobu et al focused their study on the role of nuclear factor of activated T cells c1 (NF-ATc1) in EGCG’s effect on osteoclasts [35]. On the other hand, a study by Leichsenring, et al lacked a detailed discussion on the mechanism of EGCG [34]. A study of Oka, et al on both EGCG and TFDG also gave an incomplete description of the mechanism of the compounds’ anti-RA effects [36].…”

“…Furthermore, IL-6, TNFα, and interferon (IFN)-γ were suppressed, but anti-CII specific IgG1 antibodies were activated when CIA rats were treated for 3 weeks with a dose of 10 mg per kg of the rats’ weight [33]. EGCG at doses of 10 mg/kg for 5 days also showed anti-RA effects on pristane-induced arthritic (PIA) rats via inhibition of myeloperoxidase (MPO) [34]. When both human osteoclasts of peripheral blood monocytes and mice were treated for 15 days with a dose of 20 and 50 μM, CTR, carbonic anhydrase II, cathepsin K, α-v integrin, β-3 integrin, and NF-ATc1 were downregulated [35].…”

Encapsulation of epigallocatechin-3-gallate into albumin nanoparticles improves pharmacokinetic and bioavailability in rat model

“…Two groups of Wistar albino rats weighing around 200-250 g were used to study the pharmacokinetics after a single oral administration of free EGCG and Alb-NP-EGCG at a dose of 10 mg kg −1 (Leichsenring et al 2016;Stringer et al 2017). Rats were sacrificed at a time interval of 1, 2, 3, 4, 6, 8, and 24 h after oral drug administration and the blood and tissue samples (liver, kidney, spleen, and brain) were collected.…”

“…Green tea consumption has been associated with multiple health benefits, particularly its active derivative epigallocatechin-3-gallate (EGCG) has shown to modulate many pharmacological properties in cancer (Lambert and Yang 2003;Thangapazham et al 2007;Rahmani et al 2015), inflammatory (Tominari et al 2015;Leichsenring et al 2016) and cardiovascular diseases (Eng et al 2018). Further, EGCG has shown the potential to inhibit reactive oxygen species and apoptosis, chelate metals, and modulate multiple signaling pathways (Hechler et al 2006;Karatas et al 2009;Schroeder et al 2009).…”

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

“…For example, a randomized, double-blind, placebo-controlled trial showed that green tea containing O -methylated catechins reduces symptoms of Japanese cedar pollinosis [ 100 ]. In an animal model of arthritis, the therapeutic effect of EGCG was reported to be comparable to that of methotrexate, a well-known anti-rheumatoid arthritis drug [ 101 ]. CMDA provided information on the interaction of catechins with proteins related to immunological diseases and two studies [ 102 , 103 ] have been discussed earlier [ 5 ].…”