Anti-inflammatory effects of daidzein on primary astroglial cell culture.
BACKGROUND
Alzheimer's disease is the common cause of dementia in old people. The pathological hallmarks of Alzheimer's disease include neuronal loss, deposition of amyloid-beta, and presence of neurofibrillary tangles. The endogenous steroid estrogen has been shown to affect neuronal growth, differentiation and survival, while isoflavones also have a neuroprotective effect on human cortical neurons. Daidzein, however, has a superior neuron-protective effect to other isoflavones. The present study is to determine whether daidzein is able to inhibit the production of pro-inflammatory mediators under amyloid-beta and lipopolysaccharide stimulation.


METHODS
Astrocyte cells were stimulated with amyloid-beta or lipopolysaccharide in the absence and presence of diadzein. Nitric oxide released into the culture media was determined using the Griess reaction, and concentrations of IL-1, IL-6, TNF-alpha and estrogen receptor gene expression were measured by semi-quantitative real-time polymerase chain reaction assay.


RESULTS
Diadzein-treatment increases astrocyte cell counts and attains its maximal effect at the 10(-12)M concentration. The addition of 20 microM amyloid-beta or 10(-6) g/ml LPS can significantly decrease the viability of astrocytes, up-regulated IL-1, IL-6, TNF-alpha mRNA and estrogen receptor expression; in addition, 1-h daidzein pre-treatment can restore the decreased viability of astrocytes induced by amyloid-beta or lipopolysaccharide as well as down-regulate their mRNA expression.


CONCLUSIONS
It seems that this response is estrogen receptor-mediated. These results further increase the possibility that daidzein may have potential to ameliorate the inflammatory process and also alleviate the risk of Alzheimer's disease progression.
Liu
Man-Hai
MH
Graduate Institute of Pharmacy, Taipei Medical University, Taipei, Taiwan, Republic of China.
Lin
Yu-Shan
YS
Sheu
Shiow-Yunn
SY
Sun
Jui-Sheng
JS
D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007529:Isoflavones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D007529:Isoflavones; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C004742:daidzein