Salvianolic acids improve liver lipid metabolism in ovariectomized rats via blocking STAT-3/SREBP1 signaling

Salvianolic acids improve liver lipid metabolism in ovariectomized rats via blocking STAT-3/SREBP1 signaling
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丹酚酸通过阻断 STAT-3/SREBP1 信号传导改善卵巢切除大鼠的肝脏脂质代谢

DOI:
10.1016/s1875-5364(18)30125-0
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发表时间:
2018-11-01
影响因子:
4.6
通讯作者:
Li Yuan
Li Yuan
中科院分区:
医学2区
文献类型:
--
作者:
Chen Juan;Yue Jia;Li Yuan

文献摘要

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绝经后妇女,谁降低了循环雌激素水平,更容易发展肥胖和相关的代谢疾病比绝经前妇女。由于缺乏安全有效的治疗绝经后肥胖的方法,人们将焦点转向天然产品作为替代疗法。丹参总黄酮酸(TSA)是丹参的主要水溶性成分。丹参酮酸(SA)是TSA的主要成分。丹参素酸,包括TSA和SA,广泛用于传统中药中。本研究采用去卵巢大鼠模型和LO 2细胞模型,观察丹参酮酸对大鼠体重增加和肝脏脂肪变性的影响。丹参酮酸可降低去卵巢(OVX)诱导的体重增加,抑制肝脏脂肪生成基因如固醇调节元件结合蛋白(SREBP)1、脂肪酸合成酶(FAS)和硬脂酰辅酶A去饱和酶(SCD)1的表达,降低肝脏甘油三酯(TG)和总胆固醇(TC)。在分子机制上,丹参素能抑制去卵巢和高糖诱导的信号转导子和转录激活子(STAT)-3的磷酸化。在LO 2细胞中,通过siRNA抑制STAT-3减弱高糖诱导的SREBP 1和TG表达增加。丹参素酸可降低高糖诱导的LO 2细胞SREBP 1和TG表达上调。总之,这些结果表明,丹参素酸显着减轻脂质代谢紊乱和预防绝经后肥胖。其机制可能与STAT-3信号通路的调节有关。
Postmenopausal women, who have reduced circulating estrogen levels, are more prone to develop obesity and related metabolic diseases than premenopausal women. The absence of safe and effective treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Total salvianolic acids (TSA) are the major water-soluble ingredients of Danshen. Salvianolic acid (SA) is the major constituent of the TSA. Salvianolic acids, including TSA and SA, are widely used in traditional Chinese medicine. In the present study, ovariectomized rats and LO2 cells were used to study the effects of salvianolic acids on body weight gain and hepatic steatosis. Salvianolic acids reduced ovariectomy (OVX)-induced body weight gain, attenuated the expressions of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP) 1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decreased the liver triglyceride (TG) and total cholesterol (TC). For the molecular mechanisms, OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 was inhibited by salvianolic acids treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased expression of SREBP1 and TG induced by high glucose. Salvianolic acids reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that salvianolic acids markedly alleviated the lipid metabolism disorders and protected against the postmenopausal obesity. The underlying mechanism was probably associated with the regulation of STAT-3 signaling.