Neferine Ameliorates Sepsis-Induced Myocardial Dysfunction Through Anti-Apoptotic and Antioxidative Effects by Regulating the PI3K/AKT/mTOR Signaling Pathway.
Neferine Ameliorates Sepsis-Induced Myocardial Dysfunction Through Anti-Apoptotic and Antioxidative Effects by Regulating the PI3K/AKT/mTOR Signaling Pathway.
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Neferine 通过调节 PI3K/AKT/mTOR 信号通路的抗细胞凋亡和抗氧化作用改善脓毒症引起的心肌功能障碍
DOI：
10.3389/fphar.2021.706251
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发表时间：
2021
影响因子：
5.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Qi Z;Wang R;Liao R;Xue S;Wang Y
脓毒症心肌病是严重脓毒症的常见并发症，是重症监护病房死亡的主要原因之一。因此，寻找有效的治疗靶点迫在眉睫。甲基莲心碱是从莲（Nelumbo nucifera Gaertn.）成熟种子的绿色胚中提取的生物碱，据报道其表现出各种生物活性和药理学性质。本研究旨在探讨甲基莲心碱对脂多糖（LPS）诱导的心肌损伤的保护作用及其机制。采用脂多糖（LPS）诱导的心功能不全小鼠模型，研究甲基莲心碱的保护作用。在本研究中，我们证明甲基莲心碱显着改善心功能和生存率，并改善心脏组织的形态学损伤的LPS诱导的小鼠。甲基莲心碱还改善细胞活力和线粒体功能，并减少细胞凋亡和活性氧的产生在LPS处理的H9 c2细胞。此外，甲基莲心碱显着上调Bcl-2的表达和抑制裂解caspase 3活性在LPS诱导的小鼠心脏组织和H9 c2细胞。此外，甲基莲心碱还在体内和体外上调磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素机制靶点（PI 3 K/AKT/mTOR）信号通路。相反，LY 294002（PI 3 K抑制剂）逆转甲基莲心碱在LPS诱导的H9 c2细胞中的保护作用。因此，我们的研究结果表明甲基莲心碱通过激活PI 3 K/AKT/mTOR信号通路来改善LPS诱导的心功能障碍，并为治疗LPS诱导的心功能障碍提供了有前途的治疗剂。
Septic cardiomyopathy is a common complication of severe sepsis, which is one of the leading causes of death in intensive care units. Therefore, finding an effective therapy target is urgent. Neferine is an alkaloid extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., which has been reported to exhibit various biological activities and pharmacological properties. This study aims to explore the protective effects of neferine against lipopolysaccharide (LPS)-induced myocardial dysfunction and its mechanisms. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of neferine. In this study, we demonstrated that neferine remarkably improved cardiac function and survival rate and ameliorated morphological damage to heart tissue in LPS-induced mice. Neferine also improved cell viability and mitochondrial function and reduced cell apoptosis and the production of reactive oxygen species in LPS-treated H9c2 cells. In addition, neferine significantly upregulated Bcl-2 expression and suppressed cleaved caspase 3 activity in LPS-induced mouse heart tissue and H9c2 cells. Furthermore, neferine also upregulated the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway in vivo and in vitro. Conversely, LY294002 (a PI3K inhibitor) reversed the protective effect of neferine in LPS-induced H9c2 cells. Our findings thus demonstrate that neferine ameliorates LPS-induced cardiac dysfunction by activating the PI3K/AKT/mTOR signaling pathway and presents a promising therapeutic agent for the treatment of LPS-induced cardiac dysfunction.
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影响因子：
3.7
作者：
Braun CK;Kalbitz M;Halbgebauer R;Eisele P;Messerer DAC;Weckbach S;Schultze A;Braumüller S;Gebhard F;Huber-Lang MS
通讯作者：
Huber-Lang MS
影响因子：
5.3
作者：
Chen L;Liu P;Feng X;Ma C
通讯作者：
Ma C
脂联素通过调节 Cx43/PI3K/AKT 途径减弱脂多糖诱导的细胞凋亡
影响因子：
5.6
作者：
Liu L;Yan M;Yang R;Qin X;Chen L;Li L;Si J;Li X;Ma K
通讯作者：
Ma K
影响因子：
6
作者：
Baskaran, Rathinasamy;Poornima, Paramasivan;Padma, Viswanadha Vijaya
通讯作者：
Padma, Viswanadha Vijaya
影响因子：
4.6
作者：
Priya LB;Baskaran R;Huang CY;Padma VV
通讯作者：
Padma VV