Cardamonin from Alpinia rafflesiana inhibits inflammatory responses in IFN-γ/LPS-stimulated BV2 microglia via NF-κB signalling pathway.
The increasing prevalence of neurodegenerative diseases has prompted investigation into innovative therapeutics over the last two decades. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the therapeutic choices to control and suppress the symptoms of neurodegenerative diseases. However, NSAIDs-associated gastropathy has hampered their long term usage despite their clinical advancement. On the natural end of the treatment spectrum, our group has shown that cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Alpinia rafflesiana exerts potential anti-inflammatory activity in activated macrophages. Therefore, we further explored the anti-inflammatory property of cardamonin as well as its underlying mechanism of action in IFN-γ/LPS-stimulated microglial cells. In this investigation, cardamonin shows promising anti-inflammatory activity in microglial cell line BV2 by inhibiting the secretion of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). The inhibition of NO and PGE(2) by cardamonin are resulted from the reduced expression of inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2), respectively. Meanwhile the suppressive effects of cardamonin on TNF-α, IL-1β and IL-6 were demonstrated at both protein and mRNA levels, thus indicating the interference of upstream signal transduction pathway. Our results also validate that cardamonin interrupts nuclear factor-kappa B (NF-κB) signalling pathway via attenuation of NF-κB DNA binding activity. Interestingly, cardamonin also showed a consistent suppressive effect on the cell surface expression of CD14. Taken together, our experimental data provide mechanistic insights for the anti-inflammatory actions of cardamonin in BV2 and thus suggest a possible therapeutic application of cardamonin for targeting neuroinflammatory disorders.
Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia.
Yuh-Lit
YL
Chow
Ka-Heng
KH
Lee
Sharmili
S
Vidyadaran
Nordin Haji
NH
Lajis
M Nadeem
MN
Akhtar
Daud Ahmad
DA
Israf
Ahmad
A
Syahida
D032429:Alpinia; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D009573:Nitrites / Q000276:immunology
D000893:Anti-Inflammatory Agents; D047188:Chalcones; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D009569:Nitric Oxide; D007371:Interferon-gamma; D004247:DNA; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C436747:cardamonin; D015232:Dinoprostone