Estrogen receptor α mediates the effects of notoginsenoside R1 on endotoxin-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes.
Estrogen receptors (ERs) are important for preventing endotoxin-induced myocardial dysfunction. Therefore, plant-derived phytoestrogens, which target ERs may also affect endotoxin-induced toxicity in cardiomyocytes. Our previous study revealed that notoginsenoside-R1 (NG-R1), a predominant phytoestrogen from Panax notoginseng, protects against cardiac dysfunction. However, the effects of NG-R1 on cardiomyocytes and the precise cellular/molecular mechanisms underlying its action remain to be elucidated. In the present study, pretreatment with NG-R1 suppressed the lipopolysaccharide (LPS)-induced degradation of inhibitor of nuclear factor-κB (NF-κB) α, the activation of NF-κB and caspase-3, and the subsequent myocardial inflammatory and apoptotic responses in H9c2 cardiomyocytes. An increase in the mRNA and protein expression of ERα was also observed in the NG-R1-treated cardiomyocytes. However, the expression pattern of ERβ remained unaltered. Furthermore, the cardioprotective properties of NG-R1 against LPS-induced apoptosis and the inflammatory response in cardiomyocytes were attenuated by ICI 182780, a non-selective ERα antagonist, and methyl-piperidino-pyrazole, a selective ERα antagonist. These findings suggested that NG-R1 reduced endotoxin-induced cardiomyocyte apoptosis and the inflammatory response via the activation of ERα. Therefore, NG-R1 exerted direct anti-inflammatory and anti-apoptotic effects on the cardiomyocytes, representing a potent agent for the treatment of myocardial inflammation during septic shock.
Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Lei
L
Zhong
Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Xing-Lu
XL
Zhou
Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Yan-Song
YS
Liu
Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Yi-Min
YM
Wang
Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Fei
F
Ma
Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Bao-Liang
BL
Guo
Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Zhao-Qi
ZQ
Yan
Department of Internal Medicine, Cancer Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang 150040, P.R. China.
Qing-Yuan
QY
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000378:metabolism; D005786:Gene Expression Regulation; D036145:Ginsenosides / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000096:biosynthesis; D053723:Panax notoginseng / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha
D004731:Endotoxins; D047628:Estrogen Receptor alpha; D036145:Ginsenosides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C072936:notoginsenoside R1