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Article

Diospyrin Modulates Inflammation in Poly I:C-Induced Macrophages via ER Stress-Induced Calcium-CHOP Pathway

1
Department of Pathology, College of Korean Medicine, Gachon University, Seong-nam 13120, Korea
2
Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan
3
Department of Chemistry, University of Swabi, Anbar 23561, KPK, Pakistan
*
Author to whom correspondence should be addressed.
Processes 2020, 8(9), 1050; https://doi.org/10.3390/pr8091050
Received: 29 July 2020 / Revised: 19 August 2020 / Accepted: 25 August 2020 / Published: 27 August 2020
(This article belongs to the Special Issue Pharmacodynamics Modeling of Anti-inflammatory Drugs)
Diospyrin, plant-derived bisnaphthoquinonoid, is known to have anticancer activity. However, pharmacological activity of diospyrin on viral infection is not well known. We investigated effects of diospyrin on macrophages induced by polyinosinic-polycytidylic acid (poly I:C), a mimic of double-stranded viral RNA. Various cytokines, intracellular calcium, nitric oxide (NO), phosphorylated p38 MAPK, and phosphorylated ERK1/2 as well as mRNA expressions of transcription factors were evaluated. Diospyrin significantly reduced NO production, granulocyte-macrophage colony-stimulating factor production, and intracellular calcium release in poly I:C-induced RAW 264.7. The phosphorylation of p38 MAPK and ERK1/2 was also significantly suppressed. Additionally, diospyrin inhibited mRNA levels of nitric oxide synthase 2, C/EBP homologous protein (CHOP), calcium/calmodulin dependent protein kinase II alpha, signal transducers and activators of transcription 1 (STAT1), STAT3, STAT4, Janus kinase 2, first apoptosis signal receptor, c-Jun, and c-Fos in poly I:C-induced RAW 264.7. Taken together, this study represents that diospyrin might have the inhibitory activity against viral inflammation such as excessive production of inflammatory mediators in poly I:C-induced RAW 264.7 via ER stress-induced calcium-CHOP pathway. View Full-Text
Keywords: diospyrin; poly I:C; viral infection; p38 MAPK; ERK1/2; CHOP; STAT; ER stress; calcium; cytokine diospyrin; poly I:C; viral infection; p38 MAPK; ERK1/2; CHOP; STAT; ER stress; calcium; cytokine
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MDPI and ACS Style

Kim, H.-J.; Khan, I.; Shahidullah, A.; Halimi, S.M.A.; Rauf, A.; Lee, J.-Y.; Kim, Y.-J.; Kim, B.-Y.; Park, W. Diospyrin Modulates Inflammation in Poly I:C-Induced Macrophages via ER Stress-Induced Calcium-CHOP Pathway. Processes 2020, 8, 1050. https://doi.org/10.3390/pr8091050

AMA Style

Kim H-J, Khan I, Shahidullah A, Halimi SMA, Rauf A, Lee J-Y, Kim Y-J, Kim B-Y, Park W. Diospyrin Modulates Inflammation in Poly I:C-Induced Macrophages via ER Stress-Induced Calcium-CHOP Pathway. Processes. 2020; 8(9):1050. https://doi.org/10.3390/pr8091050

Chicago/Turabian Style

Kim, Hyun-Ju, Inamullah Khan, Adnan Shahidullah, Syed M.A. Halimi, Abdur Rauf, Ji-Young Lee, Young-Jin Kim, Bong-Youn Kim, and Wansu Park. 2020. "Diospyrin Modulates Inflammation in Poly I:C-Induced Macrophages via ER Stress-Induced Calcium-CHOP Pathway" Processes 8, no. 9: 1050. https://doi.org/10.3390/pr8091050

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