Berberine modulates hyper-inflammation in mouse macrophages stimulated with polyinosinic-polycytidylic acid via calcium-CHOP/STAT pathway

• Published in: Scientific reports Vol. 11; no. 1; p. 11298
• Main Authors: Kim, Hyun-Ju, Kim, Young-Jin, Park, Wansu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-05-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/250; 692/420; Ammonium; Ammonium salts; Apoptosis; Berberine; Calcium; Calcium (intracellular); Calcium (reticular); CD95 antigen; CHOP protein; Double-stranded RNA; Endoplasmic reticulum; Extracellular signal-regulated kinase; Gene expression; Granulocyte-macrophage colony-stimulating factor; Humanities and Social Sciences; Inflammation; Kinases; Macrophage inflammatory protein; Macrophages; MAP kinase; multidisciplinary; Nitric oxide; Phosphorylation; Polyinosinic:polycytidylic acid; Prostaglandin E2; Protein kinase; RANTES; Science; Science (multidisciplinary); Stat1 protein; Stat3 protein; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-90752-z

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.