12-oxo-phytodienoic acid, a plant-derived oxylipin, attenuates lipopolysaccharide-induced inflammation in microglia

Abstract

Jasmonates are plant lipid-derived oxylipins that act as key signaling compounds in plant immunity, germination, and development. Although some physiological activities of natural jasmonates in mammalian cells have been investigated, their anti-inflammatory actions in mammalian cells remain unclear. Here, we investigated whether jasmonates protect mouse microglial MG5 cells against lipopolysaccharide (LPS)-induced inflammation. Among the jasmonates tested, only 12-oxo-phytodienoic acid (OPDA) suppressed LPS-induced expression of the typical inflammatory cytokines interleukin-6 and tumor necrosis factor α. In addition, only OPDA reduced LPS-induced nitric oxide production through a decrease in the level of inducible nitric oxide synthase. Further mechanistic studies showed that OPDA suppressed neuroinflammation by inhibiting nuclear factor κB and p38 mitogen-activated protein kinase signaling in LPS-activated MG5 cells. In addition, OPDA induced expression of suppressor of cytokine signaling-1 (SOCS-1), a negative regulator of inflammation, in MG5 cells. Finally, we found that the nuclear factor erythroid 2-related factor 2 signaling cascade induced by OPDA is not involved in the anti-inflammatory effects of OPDA. These results demonstrate that OPDA inhibited LPS-induced cell inflammation in mouse microglial cells via multiple pathways, including suppression of nuclear factor κB, inhibition of p38, and activation of SOCS-1 signaling.

Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling

“…LPS leads to glial activation, that is astrocytosis and reactive microglia, which releases inflammatory cytokines such as TNF-α and IL-1β. These inflammatory mediators are involved in various neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and cerebral ischemia [52,53,54]. Herein, we observed that LPS markedly elevated microglial activation and astrocytosis by enhancing the TLR4 receptor expression, but hesperetin ameliorated the reactive gliosis and astrocytosis by downregulating the TLR4-mediated GFAP and Iba-1 expression.…”

Carpesium divaricatum Sieb. & Zucc. Revisited: Newly Identified Constituents from Aerial Parts of the Plant and Their Possible Contribution to the Biological Activity of the Plant

“…proved that the compound was (9 S ,13 R )-12-OPDA, i.e., (+)- trans -12-OPDA [40]. Except for the activity as a plant hormone, 12-OPDA exerted cytoprotective effects in human neuroblastoma SH-SY5Y cells subjected to oxidative stress [41], mitigated LPS-induced inflammation in microglia [42], inhibited proliferation of human breast cancer cells [43], and demonstrated antileishmanial activity [44]. Thus, we decided to check whether or not the compound may contribute to the overall activity of C. divaricatum .…”

Distribution analysis of jasmonic acid‐related compounds in developing Glycine max L. (soybean) seeds using mass spectrometry imaging and liquid chromatography–mass spectrometry

“…The effects of JA‐related oxylipins on mammals have attracted much attention because of their structural similarities to mammalian oxylipins such as prostaglandins and leukotrienes. Known in vitro and in vivo effects of JA‐related oxylipins include anti‐inflammatory and anti‐cancer effects, and anti‐ageing properties on human skin 29,30 . Therefore, the seed coat of developing G. max seeds may be a promising source of these JA‐related oxylipins.…”

“…Known in vitro and in vivo effects of JA-related oxylipins include anti-inflammatory and anti-cancer effects, and anti-ageing properties on human skin. 29,30 Therefore, the seed coat of developing G. max seeds may be a promising source of these JA-related oxylipins. Pharmacokinetic analyses (i.e., post-consumption tissue-localisation analyses of phytochemicals) have been conducted using MALDI-MSI.…”