Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis

Abstract

Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically, PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO, and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system (CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.

The dual face of microglia (M1/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases

“…As a result, the suppressive impact of PEGA on the release of IL-6 in macrophages/microglia and TNF-α in microglia may contribute to the agent's amelioration of EAE. PEGA's inhibitory effects on NO, TNF-α, and IL-6 are consistent with the previously reported effects of GA and GA-like substances on immune cells in both in vivo and in vitro studies (Stegnjai et al, 2022b).…”

“…The phenethyl ester of gallic acid (PEGA) was developed to enhance gallic acid bioavailability and consequently its therapeutic potential. PEGA has been demonstrated to affect the inflammatory activities of T-cells and macrophages/microglia in an in vivo study of its effects on encephalitogenic cells (Stegnjai et al, 2022b) PEGA lowered the inflammatory potency of T-cells and microglia by inhibiting their ability to produce or release IL-17 and IFN-γ, as well as IL-6 and NO. Additionally, it significantly limits ongoing inflammatory responses against the CNS while also alleviating EAE.…”

Complete Freund’s adjuvant as a confounding factor in multiple sclerosis research

“…Infiltrates were observed in both the white and the gray matter of the spinal cord and also in the brain ( 68 ). This model has proven useful for evaluating the therapeutic efficacy of novel agents ( 73 , 74 ). We are currently investigating cellular and molecular mechanisms behind the pathogenesis of CNS autoimmunity in this model in detail.…”