Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells

Abstract

Inflammation is a complex physiological process that poses a serious threat to people’s health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.

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

“…Under the stimulation of LPS, RAW26.7 cells activate inducible iNOS and COX enzyme systems, leading to cytokines like NO and PGE2 release [33]. Shan et al demonstrated that PCA1, an isomeride of PCA2, showed no effect on COX-2 and PGE2 in RAW264.7 cells [9]. However, in our study, PCA2 attenuated COX-2 expression and PGE2 release, which is different from PCA1 (Figs 1 and 2).…”

“…And B-type proanthocyanidins are bind together via C4β!C8, C4β!C6, C4α!C8 or C4α!C6 bonds, while A-type proanthocyanidins have another interflavan bond C2β!O7, and procyanidins A1, A2, B1, B2, B3 are dimers, procyanidin C1 is trimer [27]. Increasing evidence has demonstrated that procyanidin A1 has anti-inflammatory and anti-oxidative effects on LPS-stimulated RAW264.7 cells [9]. Procyanidin B1, B2, and C1 showed anti-inflammatory and oxidative activities in human monocytes [28].…”

“…Inflammatory processes include vascular reactions and white blood cell reactions, which are achieved through the action of a series of chemical factors [ 8 ]. A monocyte/macrophage-like cell line plays a valuable role in the inflammatory process [ 9 ]. Thus, RAW264.7 macrophage is the most generally employed for drug screening for anti-inflammatory activity in vitro [ 9 ].…”

“…A monocyte/macrophage-like cell line plays a valuable role in the inflammatory process [ 9 ]. Thus, RAW264.7 macrophage is the most generally employed for drug screening for anti-inflammatory activity in vitro [ 9 ]. LPS, toll-like receptor 4 (TLR4) agonist, induces inflammation response on the macrophage, which induces pro-inflammatory cytokines release [ 10 , 11 ].…”

Bioactive role of plant stress hormone methyl jasmonate against lipopolysaccharide induced arthritis

“…The result of study indicates LPS dramatically increases the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells by activation of NF-κB and increases the expression and synthesis of inflammatory cytokines (TNF-α, IL-6, IL-1β, NO, and iNOS2). In the conclusion it was summarized that inhibition or disorder of NF-κB pathway could be potential target in the treatment of inflammation and oxidative stress (Han et al, 2019). Activated NF-κB regulates gene transcription related to host immune, inflammatory responses and oxidative stress.…”