In vitro evidence that the anti‐inflammatory effect of synthetic cinnamate‐derived dienes is directly linked to a macrophage repolarization

Abstract

The inflammatory process is a mammalian physiological reaction against infectious agents or injuries. Among the cells involved, the macrophages have a highlighted role during this process. Depending on the inflammatory context, they can polarize into pro-or anti-inflammatory profiles (M1 and M2). In this context, compounds derived from cinnamic acid have demonstrated strong evidence of anti-inflammatory activity; however, the mechanism responsible for this effect remains unclear. In this study, we investigated the anti-inflammatory activity of five cinnamate-derived dienes of synthetic origin. The compounds that did not demonstrate significant cytotoxicity were tested to assess anti-inflammatory activity (NO x ) in RAW 264.7 cells stimulated with LPS. Then, the selected compound (diene 1) was evaluated as to its ability to inhibit the secretion of pro-inflammatory cytokines (IL-1β, TNF-α, INF-γ, MCP-1, and IL-6) and increase the production of antiinflammatory cytokines (IL-13, IL-4, and IL-10). Finally, diene 1 was able to reduce the expression of TLR4 and increase the phagocytic activity of the macrophages. Gathering these results together, we conclude that diene 1 showed an important anti-inflammatory effect, and this effect is linked to its immunomodulatory characteristic. Since the M1 markers were reduced at the same time, M2 markers were increased by the treatment of the macrophages with diene 1.

Evaluation of anti‐inflammatory activity of kaurenol: Experimental evaluation and mechanistic insights

“…NO effect has already been demonstrated in LPSstimulated macrophages [23]. Furthermore, NO results are similar to C. langsdorffii leaf extract [5].…”

“…In vitro assays have been employed to elucidate the mechanisms underlying the anti-inflammatory effects [22,23]. Kaurenol showed no cytotoxic activity and inhibit NO, IL-6, and IL-10 release induced by LPS.…”

Novel ginsenoside monomer RT4 promotes colitis repair in mice by regulating miR‐144‐3p/SLC7A11 signaling pathway

“…M1 macrophages produce pro‐inflammatory cytokines such as TNF‐α, IL‐1β, IL‐6, and IL‐12. M2 macrophages secrete anti‐inflammatory cytokines such as IL‐10 and TGF‐β, which promote tissue repair [15]. It is shown that the regulatory effects of ginsenoside RT4 on cytokine production may modulate the innate immune system in mice with colitis, leading to the repair of the injury of colitis.…”