The inhibitory effects of Orengedokuto on inducible PGE2 production in BV-2 microglial cells

Abstract

Background and aim Reactive microglia has been associated with neuroinflammation caused by the production of proinflammatory molecules such as cytokines, nitric oxide, and prostaglandins. The overexpression of these molecules may provoke neuronal damage that can cause neurodegenerative diseases. A traditional herbal medicine, Orengedokuto (OGT), has been widely used for treating inflammation-related diseases. However, how it influences neuroinflammation remains poorly understood. Experimental procedure This study investigated the effects of OGT on inflammatory molecule induction in BV-2 microglial cells using real-time RT-PCR and ELISA. An in vivo confirmation of these effects was then performed in mice. Results and conclusion OGT showed dose-dependent inhibition of prostaglandin E2 (PGE2) production in BV-2 cells stimulated with lipopolysaccharide (LPS). To elucidate the mechanism of PGE2 inhibition, we examined cyclooxygenases (COXs) and found that OGT did not suppress COX-1 expression or inhibit LPS-induced COX-2 upregulation at either the transcriptional or translational levels. In addition, OGT did not inhibit COX enzyme activities within the concentration that inhibited PGE2 production, suggesting that the effect of OGT is COX-independent. The inhibitory effects of OGT on PGE2 production in BV-2 cells were experimentally replicated in primary cultured astrocytes and mice brains. OGT can be useful in the treatment of neuroinflammatory diseases by modulating PGE2 expression.

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“…When microglial cells are activated, the secretion of pro-inflammatory cytokines including TNF-α and IL-1β, increases leading to a neuroinflammatory response ( López and Ballaz, 2020 ). The activation of microglial cells is also associated with the release of microsomal PGE synthase (mPGES)-1 ( Nagano et al, 2021 ) which is an inducible enzyme involved in the synthesis of prostaglandins E2 (PGE 2 ) leading to neurodegenerative diseases ( Chini et al, 2020 , Iwata et al, 2021 ). Fig.…”