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2017 ; 242
(5
): 527-535
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Histone deacetylase-high mobility group box-1 pathway targeted by hypaconitine
suppresses the apoptosis of endothelial cells
#MMPMID28056545
Bai Y
; Du S
; Li F
; Huang F
; Deng R
; Zhou J
; Chen D
Exp Biol Med (Maywood)
2017[Mar]; 242
(5
): 527-535
PMID28056545
show ga
Hypaconitine is an active component of Aconitum carmichaelii Debx, a Chinese
medicinal herb for the treatment of cardiovascular diseases, but the mechanism
underlying its effect remains elusive. In this study, we found that hypaconitine,
rather than aconitum alkaloids in A. carmichaelii (e.g. aconitine, mesaconitine
and benzoylaconitine), prevented endothelial cells from damage due to oxidized
low-density lipoprotein (oxLDL) challenge. Cleaved caspase 3 expression in
endothelial cells was up-regulated by oxLDL and markedly attenuated by
hypaconitine, suggesting that hypaconitine inhibited the oxLDL-induced cell
apoptosis. Microarray analysis revealed that histone deacetylase 3 (HDAC3) was
significantly increased by hypaconitine. The cytoplasmic relocation and
extracellular release of high-mobility group box 1 (HMGB1, an HDAC3 downstream
effector) in endothelial cells were significantly increased by oxLDL and markedly
decreased by hypaconitine. The effect of hypaconitine on the oxLDL-induced
apoptosis and HMGB1 release in endothelial cells was significantly reduced by the
suppression of HDAC3 by siRNA or a specific inhibitor. Thus, this study proves
that the histone deacetylase-HMGB1 pathway targeted by hypaconitine suppresses
the apoptosis of endothelial cells. Our findings are of therapeutic significance
and provide the potential of hypaconitine exploitation. Impact statement First,
our study shows the antiapoptosis effect of Aconitum carmichaelii and its active
component hypaconitine on endothelial cells. It may provide new strategies for
the treatment of diseases involving endothelium damage. Second, this finding
indicates the function of hypaconitine in regulating HDAC3-HMGB1 pathway, which
suggests a new anti-inflammatory therapy. Third, due to its poisonousness, A.
carmichaelii is always used with caution in clinics. Thus, the identification of
hypaconitine as an active component of A. carmichaelii could contribute to the
development of toxicity-decreasing procedure for A. carmichaelii.