Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes.
BACKGROUND
Neuritic plaques, a neuropathologic hallmark of Alzheimer's disease, are extracellular deposits of beta-amyloid peptides (Abeta). In the central nervous system neuritic plaques are surrounded by activated microglial cells expressing proinflammatory cytokines, chemokines, and neurotoxic mediators. Long-term activation of microglial cells is suspected to contribute to the neuron loss in Alzheimer's disease.


OBJECTIVE
This study was conducted to determine whether a ginger (Zingiber officinale and Alpinia galanga) extract (GE) can dampen the activation of THP-1 cells by lipopolysaccharide, proinflammatory cytokines, and fibrillar amyloid peptide Abeta(1-42), a major component of neuritic plaques.


METHODS
THP-1 cells, a human monocytic cell line with properties similar to human microglial cells, were incubated with GE or control medium alone for 1 hour, and then with reincubated lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) or fibrillar Abeta(1-42) for an additional hour. The extent of THP-1 cell activation was determined by measuring mRNA levels of TNF-alpha and IL-1beta, cyclooxygenase-2 (COX-2), macrophage inflammatory protein 1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma inducible protein 10 (IP-10).


RESULTS
The results document that the GE used in this study inhibits LPS, cytokine, and amyloid Abeta peptide-induced expression of the proinflammatory genes TNF-alpha, IL-1beta, COX-2, MIP-alpha, MCP-1, and IP-10. The data provide experimental evidence that ginger can inhibit the activation of human monocytic THP-1 cells by different proinflammatory stimuli and reduce the expression of a wide range of inflammation-related genes in these microglial-like cells.


CONCLUSIONS
The findings suggest that GE may be useful in delaying the onset and the progression of neurodegenerative disorders involving chronically activated microglial cells in the central nervous system.
Grzanna
Reinhard
R
RMG Biosciences, Inc., Baltimore, MD, USA.
Phan
Phong
P
Polotsky
Anna
A
Lindmark
Lars
L
Frondoza
Carmelita G
CG
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D018925:Chemokines / Q000037:antagonists & inhibitors*; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D020939:Zingiber officinale; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D016229:Amyloid beta-Peptides; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases