Abstract

Berberine is a well-known quaternary ammonium salt that is usually found in the roots of such plants as Phellodendron amurense and Coptis chinensis. However, the effects of berberine on double-stranded RNA (dsRNA)-induced macrophages have not been fully reported. In this study, we examined the anti-inflammatory effects of berberine on dsRNA [polyinosinic-polycytidylic acid; poly I:C]-induced macrophages. Levels of nitric oxide (NO), Prostaglandin E2 (PGE2), first apoptosis signal receptor (Fas; CD95), cytokines, intracellular calcium, phosphorylated I-kappa-B-alpha (IkB-α), phosphorylated p38 mitogen-activated protein kinase (MAPK), phosphorylated ERK1/2, phosphorylated signal transducer and activated transcription 3 (STAT3), and mRNA expression of inflammatory genes in poly I:C-induced RAW 264.7 mouse macrophages were evaluated. Berberine significantly inhibited the production of NO, PGE2, Fas, GM-CSF, LIF, LIX, RANTES, and MIP-2 as well as calcium release in poly I:C-induced RAW 264.7 cells at concentrations of up to 50 μM. Berberine also significantly inhibited the phosphorylation of p38 MAPK, ERK1/2, IkB-α, and STAT3 in poly I:C-induced RAW 264.7 cells. Additionally, berberine significantly decreased the mRNA expressions of Chop (GADD153), Stat1, Stat3, and Fas in poly I:C-induced RAW 264.7 cells. Taken together, berberine has anti-inflammatory properties related to its inhibition of NO, PGE2, Fas, GM-CSF, LIF, LIX, RANTES, and MIP-2 in dsRNA-induced macrophages via the endoplasmic reticulum stress-related calcium-CHOP/STAT pathway.

Highlights

  • Berberine is a well-known quaternary ammonium salt that is usually found in the roots of such plants as Phellodendron amurense and Coptis chinensis

  • Jiang et al reported that berberine suppresses IL-1β secretion that was induced by the activation of the NLRP3 inflammasome in m­ acrophages[2]

  • Berberine is a well-known quaternary ammonium salt that is usually found in the roots of such plants as Phel‐ lodendron amurense (Amur corktree), Berberis vulgaris, Berberis aristata, Mahonia aquifolium (Oregon grape), Hydrastis Canadensis, Xanthorhiza simplicissima, Cop‐ tis chinensis (Chinese goldthread), Tinospora cordifolia, Argemone mexicana, and Eschscholzia californica (Californian poppy)[7]

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Summary

Introduction

Berberine is a well-known quaternary ammonium salt that is usually found in the roots of such plants as Phellodendron amurense and Coptis chinensis. Berberine significantly inhibited the production of NO, PGE2, Fas, GM-CSF, LIF, LIX, RANTES, and MIP-2 as well as calcium release in poly I:C-induced RAW 264.7 cells at concentrations of up to 50 μM. Inflammation is a necessary immunoreaction against pathogenic infection in the human body It sometimes cause hyper-production of pro-inflammatory mediators, such as nitric oxide (NO), cytokines, chemokines, and prostaglandins. Macrophages produce many kinds of inflammatory mediators, including NO, Prostaglandin E2 (PGE2), first apoptosis signal receptor (Fas; CD95), cytokines, chemokines, growth factors, and prostaglandins, against invasive bacteria, fungi, and viruses. In these days, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has caused global disruption. Polyinosinic–polycytidylic acid (poly I:C), a synthetic analog of double-stranded

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