methyl-jasmonate and Inflammation

Neuroinflammation plays a central role in the etiology and progression of Alzheimer's disease (AD), a neurodegenerative disorder, characterized by a gradual loss of memory functions. Thus, it has been proposed that agents that could reduce inflammatory processes in AD brains might be useful for the treatment of the disease. Methyl jasmonate (MJ) is a bioactive compound, which has been reported to exhibit anti-amnesic and in vitro anti-inflammatory activities. In this study, we further examine its effects on the brain levels of biomarkers of neuroinflammation in lipopolysaccharide (LPS)-induced memory deficits in mice. Mice (n=6) were pretreated intraperitoneally with MJ (10-40mg/kg), donepezil (DP) (1mg/kg) or vehicle (10mL/kg) for 30min prior to injection of LPS (250μg/kg, i.p) daily for 7days. Thirty minutes after LPS administration on day 7, memory function was assessed using Y-maze test. After Y-maze test, the levels of biomarkers of neuroinflammation: prostaglandin E2 (PGE2), tumor necrosis factor α (TNFα) and interleukin 1β (IL1β) were estimated in brain tissue homogenates using ELISA. Expressions of positive cells of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB) and amyloid-beta (Aβ) in the prefrontal cortex were also assessed using immunohistochemistry technique. Our data showed that MJ (10, 20 and 40mg/kg) significantly (p<0.05) reversed LPS-induced memory deficits in mice. The increased brain levels of PGE2, TNFα and IL1β in LPS-treated mice were significantly (p<0.05) reduced by MJ indicating anti-neuroinflammatory activity. MJ also suppressed the expression of COX2, iNOS and NFκB, which further suggest anti-neuroinflammation. The increased brain level of Aβ in LPS-treated mice was significantly (p<0.05) suppressed by MJ suggesting anti-amyloidogenesis-like effect. Our present data showed that MJ attenuated LPS-induced memory dysfunction via mechanisms involving inhibition of pro-inflammatory mediators and beta-amyloid generation in mice.

Topics: Acetates; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Astrocytes; Biomarkers; Brain; Cyclooxygenase 2; Cyclopentanes; Inflammation; Interleukin-1beta; Lipopolysaccharides; Male; Maze Learning; Memory; Memory Disorders; Mice; Microglia; Neuroimmunomodulation; NF-kappa B; Nitric Oxide Synthase Type II; Oxylipins; Prefrontal Cortex; Tumor Necrosis Factor-alpha

Phytotherapy is becoming a treatment option in management of diseases including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH, however the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH.. BPH was induced by daily injections of testosterone propionate (TP) (3mg/kg) for 28 days.. The weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers; prostatic myeloperoxidase and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl. MeJA protects against TP-induced BPH via mechanisms that involve anti-inflammation, induction of apoptosis and inhibition of phase I drug metabolizing enzyme.

Topics: Acetates; Animals; Apoptosis; Biomarkers; Cyclopentanes; Finasteride; Inflammation; Lipids; Male; Metabolic Detoxication, Phase I; Nitric Oxide; Organ Size; Oxylipins; Prostate; Prostatic Hyperplasia; Rats, Wistar; Testosterone; Weight Gain

Methyl jasmonate is an important signaling molecule involved in plant defense as well as in the regulation of plant growth and development. Despite its various functions in plants, its effects on animal cells have not been widely studied and no report has been issued on the molecular aspects of its anti-inflammatory effect. In the present study, we investigated the in vitro anti-inflammatory properties of methyl jasmonate in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methyl jasmonate treatment effectively inhibited LPS-induced production of pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) in a concentration-dependent manner. Furthermore, it attenuated the LPS-induced activation of nuclear factor-κB (NF-κB) by suppressing the degradation of the inhibitor of κB-α (IκB-α). Additionally, methyl jasmonate dose-dependently blocked the phosphorylation of mitogen-activated protein kinases (MAPKs), i.e., p38 kinase, extracellular signal-regulated kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK), in these cells. These results suggest that methyl jasmonate attenuated the LPS-induced release of pro-inflammatory mediators and cytokines by suppressing the activation of MAPK (JNK, ERK and p38) and NF-κB signaling. This study not only demonstrated that methyl jasmonate exerts anti-inflammatory activities in macrophages but also revealed its potential as a candidate for the treatment of various inflammation-associated diseases.

Topics: Acetates; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Survival; Cyclooxygenase 2; Cyclopentanes; Cytokines; Dinoprostone; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide; Oxylipins; Plant Growth Regulators; RAW 264.7 Cells