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KMID : 0606920110190040431
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Biomolecules & Therapeutics
2011 Volume.19 No. 4 p.431 ~ p.437
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Betulinic Acid Inhibits LPS-Induced MMP-9 Expression by Suppressing NF-kB Activation in BV2 Microglial Cells
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Lee Jae-Won
Choi Yong-Joon
Kim Song-In
Lee Sue-Young
Kang Sang-Soo
Kim Nam-Ho
Kwon Yong-Soo
Lee Hee-Jae
Chun Wan-Joo
Kim Sung-Soo
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Abstract
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Aberrant activation of microglia has been reported to cause neuronal damages by releasing a variety of pro-infl ammatory cyto-kines. Besides where microglia become active, damages have been also observed in remote places, which is considered due to the migration of activated microglia. Therefore, an agent that could suppress abnormal activation of microglia and their sub-sequent migration might be valuable in activated microglia-related brain pathologies. The objective of the present study was to evaluate anti-infl ammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid signifi cantly attenuated LPS-induced NO production and protein expression of iNOS. Betulinic acid also signifi cantly suppressed LPS-induced release and expression of cytokines such as TNF-α and IL-1β. Furthermore, betulinic acid signifi cantly suppressed LPS-induced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major pro-infl ammatory transcription factor, was examined. Betulinic acid signifi -cantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was signifi cantly suppressed with betulinic acid. Taken together, the present study for the fi rst time demonstrates that betulinic acid possesses anti-infl ammatory activity through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.
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KEYWORD
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Betulinic acid, MMP-9, BV2 microglial cells, Lipopolysaccharide, Cytokines, NF-kB
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