Procyanidin A2, a polyphenolic compound, exerts anti-inflammatory and anti-oxidative activity in lipopolysaccharide-stimulated RAW264.7 cells

• Published in: PloS one Vol. 15; no. 8; p. e0237017
• Main Authors: Wang, Qin-Qin, Gao, Hongwei, Yuan, Renyikun, Han, Shan, Li, Xin-Xing, Tang, Meiwen, Dong, Baiqing, Li, Jun-Xiu, Zhao, Li-Chun, Feng, Jianfang, Yang, Shilin
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 05-08-2020; Public Library of Science (PLoS)
• Subjects: Anti-inflammatory agents; Antioxidants (Nutrients); Arthritis; Biology and Life Sciences; Care and treatment; Cytokines; Cytoplasm; Cytotoxicity; Engineering; Extracellular signal-regulated kinase; Grape seed extract; Health aspects; Immunofluorescence; Inflammation; Interleukin; Interleukin 6; Kinases; Lipopolysaccharides; MAP kinase; Medicine; Medicine and Health Sciences; Metabolic pathways; mRNA; NF-κB protein; Nitric oxide; Nuclei (cytology); Oligomeric proanthocyanidins; Oxidative stress; Oxygen; Pathways; Pharmacy; Polymerization; Procyanidins; Prostaglandin E2; Protein kinase; Proteins; Reactive oxygen species; Research and Analysis Methods; Seeds; Statistical analysis; Testing; Toxicity; Translocation; Tumor necrosis factor-α; China; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0237017

Procyandin A2 (PCA2) is a polyphenolic compound which is isolated from grape seeds. It has been reported that PCA2 exhibits antioxidative and anti-inflammatory effects, but its molecular mechanism is still poorly understood. This study tests the hypothesis that PCA2 suppresses lipopolysaccharide (LPS)-induced inflammation and oxidative stress through targeting the nuclear factor-[kappa]B (NF-[kappa]B), mitogen-activated protein kinase (MAPK), and NF-E2-related factor 2 (Nrf2) pathways in RAW264.7 cells. PCA2 (20, 40, 80 [mu]M) exhibited no significant cytotoxicity in RAW264.7 cells and showed an inhibitory effect on an LPS-induced nitrite level. Pro-inflammatory cytokines like tumor necrosis factor-[alpha] (TNF-[alpha]), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO), and reactive oxygen species (ROS) were suppressed by PCA2 with a concentration range of 0-80 [mu]M. The mRNA levels of TNF-[alpha] and IL-6 were inhibited by PCA2 (80 [mu]M). The hallmark-protein expression of the NF-[kappa]B (p-IKK[alpha]/[beta], p-I[kappa]B[alpha], and p-p65) and MAPK (p-p38, p-JNK, and p-ERK) pathways were decreased by PCA2 in LPS-stimulated RAW264.7 cells. In addition, immunofluorescence results indicated that PCA2 (80 [mu]M) promoted the translocation of NF-[kappa]B/p65 from the cytoplasm into the nucleus. PCA2 upregulated the expressions of Nrf2 and HO-1 and downregulated the expression of Keap-1. Simultaneously, PCA2 (80 [mu]M) reversed LPS-induced Nrf2 translocation from the nucleus into the cytoplasm. Collectively, PCA2 protect cells against the damage from inflammation and oxidative injury, which suggest a potential therapeutic strategy for inflammatory and oxidative stress through targeting NF-[kappa]B, MAPK, and Nrf2 pathways in RAW264.7 cells.