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Published on: January 30, 2014
Amelioration of LPS-induced inflammation response in microglia by AMPK activation
Chin-Chen Chen1, Jiun-Tsai Lin2, Yi-Fang Cheng2
1Institute of Applied Science and Engineering, Catholic Fu-Jen University, New Taipei City 24205, Taiwan.
Abstract:
Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis via modulating metabolism of glucose, lipid, and protein. In addition to energy modulation, AMPK has been demonstrated to associate with several important cellular events including inflammation. The results showed that ENERGI-F704 identified from bamboo shoot extract was nontoxic in concentrations up to 80 μM and dose-dependently induced phosphorylation of AMPK (Thr-172) in microglia BV2 cells. Our findings also showed that the treatment of BV2 with ENERGI-F704 ameliorated the LPS-induced elevation of IL-6 and TNF-α production. In addition, ENERGI-F704 reduced increased production of nitric oxide (NO) and prostaglandin E2 (PGE2) via downregulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), respectively. Moreover, ENERGI-F704 decreased activated nuclear translocation and protein level of NF-κB. Inhibition of AMPK with compound C restored decreased NF-κB translocation by ENERGI-F704. In conclusion, ENERGI-F704 exerts inhibitory activity on LPS-induced inflammation through manipulating AMPK signaling and exhibits a potential therapeutic agent for neuroinflammatory disease.
Insights
ENERGI-F704 from bamboo extract activates AMPK and reduces inflammation markers in microglia cells. This compound shows potential for treating neuroinflammatory diseases by modulating cellular energy and inflammatory pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Adenosine 5'-monophosphate-activated protein kinase (AMPK) regulates cellular energy and inflammation.
- Neuroinflammation is implicated in various neurological disorders.
Purpose of the Study:
- To investigate the anti-inflammatory effects of ENERGI-F704, a compound from bamboo shoot extract.
- To determine if ENERGI-F704's anti-inflammatory activity is mediated through AMPK signaling.
Main Methods:
- Treatment of microglia BV2 cells with ENERGI-F704.
- Assay of AMPK phosphorylation (Thr-172).
- Measurement of inflammatory markers (IL-6, TNF-α, NO, PGE2) and related protein expression (iNOS, COX-2, NF-κB).
- Inhibition of AMPK using compound C.
Main Results:
- ENERGI-F704 was nontoxic up to 80 μM and induced AMPK phosphorylation in BV2 cells.
- ENERGI-F704 reduced LPS-induced IL-6 and TNF-α production.
- ENERGI-F704 decreased nitric oxide and prostaglandin E2 production by downregulating iNOS and COX-2.
- ENERGI-F704 inhibited NF-κB activation, an effect reversed by AMPK inhibition.
Conclusions:
- ENERGI-F704 exhibits anti-inflammatory properties in microglia cells.
- The anti-inflammatory effects of ENERGI-F704 are mediated through the AMPK signaling pathway.
- ENERGI-F704 holds potential as a therapeutic agent for neuroinflammatory diseases.
