Methyl galbanate, a novel inhibitor of nitric oxide production in mouse macrophage RAW264.7 cells

Abstract

It is well known that inflammation is associated with various neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. An inflammatory mediator, nitric oxide (NO), is produced by inducible NO synthase (iNOS) in microglia and seems to be one of the possible causes of neurodegeneration. Several natural and synthetic compounds which exert anti-inflammatory effects by inhibiting NO production have been reported to date. The aim of this work was to investigate whether any of the 6 terpenoid coumarins (methyl galbanate, galbanic acid, farnesiferol A, badrakemone, umbelliprenin, and aurapten) isolated from Ferula szowitsiana DC. have inhibitory activity against NO production in RAW264.7 mouse macrophage cells stimulated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Of the 6 terpenoid coumarins tested, methyl galbanate significantly decreased NO production in LPS/IFN-γ-stimulated RAW264.7 cells. In the presence of methyl galbanate, LPS/IFN-γ-induced iNOS mRNA expression was significantly decreased to 52% of the level found with LPS/IFN-γ stimulation alone. Methyl galbanate slightly attenuated COX-2 mRNA expression. Using the RAW264.7-tsAM5NE co-culture system, we showed that methyl galbanate protected neuronally differentiated tsAM5NE cells from NO-induced cell death by inhibiting the production of NO. Our finding suggests that methyl galbanate may be useful for developing a new drug against neurodegenerative diseases.

Synthesis, biosynthesis and biological activities of galbanic acid – A review

“…Methyl galbanate 10 mM GA showed no effect on NO production; Methyl galbanate significantly inhibited NO production; Methyl galbanate exerts its anti-inflammatory effect by inhibiting iNOS mRNA expression (Kohno et al, 2011) Figure 2. Timeline of the proposed structures of galbanic acid by date.…”

“…In addition, methyl galbanate slightly attenuated COX-2 mRNA expression. Their findings revealed that the membrane permeability of methyl galbanate was higher than that of GA due to the presence of a hydrophobic methyl-esterified group (Kohno et al, 2011).…”

Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles

“…GBA is a lipophilic sesquiterpene coumarin and possesses different approved pharmaceutical activities. Synergism effect of GBA with penicillin G and cephalexin (Shahverdi et al, 2007), erythrocyte aggregation inhibitory properties (Mansurov & Martirosov, 1988), hepatoprotective effects through liver redox potential improving (Syrov et al, 1990), inhibition of the nitric oxide (NO) production (Kohno et al, 2011), down-regulation of androgen receptors abundance in the prostate gland (Zhang et al, 2012), anti-leishmanial activity (Iranshahi et al, 2007), and farnesyl-transferase inhibition (Cha et al, 2011) have reported for the compound.…”

Evaluation of the analgesic effect of Umbelliprenin and Umbelliprenin-morphine co-administration on the acute, chronic and neuropathic pain

“…It was shown that iNOS and NO are involved in inflammation, neurodegeneration, and NP and one of underlying mechanism of UMB is iNOS inhibitory effects. [19][20][21] UMB (0.01 mM) with morphine (1 mg/kg) potentiated morphine antinociceptive effects. UMB shows its antinociceptive effcts partly via µ receptors stimulation.…”