Benzoylaconine induces mitochondrial biogenesis in mice via activating AMPK signaling cascade.,Acta Pharmacologica Sinica

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Benzoylaconine induces mitochondrial biogenesis in mice via activating AMPK signaling cascade.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2018-10-12 , DOI: 10.1038/s41401-018-0174-8
Xiao-Hong Deng _{1,

2} , Jing-Jing Liu _{1,

2} , Xian-Jun Sun _{1,

2} , Jing-Cheng Dong _{1,

2} , Jian-Hua Huang _{1,

2}

Affiliation

The traditional Chinese medicine "Fuzi" (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. We demonstrated that Fuzi extract and its three components AC, BAC, and aconine at a concentration of 50 μM significantly increased mitochondrial mass in HepG2 cells. BAC (25, 50, 75 μM) dose-dependently promoted mitochondrial mass, mtDNA copy number, cellular ATP production, and the expression of proteins related to the oxidative phosphorylation (OXPHOS) complexes in HepG2 cells. Moreover, BAC dose-dependently increased the expression of proteins involved in AMPK signaling cascade; blocking AMPK signaling abolished BAC-induced mitochondrial biogenesis. We further revealed that BAC treatment increased the cell viability but not the cell proliferation in HepG2 cells. These in vitro results were verified in mice treated with BAC (10 mg/kg per day, ip) for 7 days. We showed that BAC administration increased oxygen consumption rate in mice, but had no significant effect on intrascapular temperature. Meanwhile, BAC administration increased mtDNA copy number and OXPHOS-related protein expression and activated AMPK signaling in the heart, liver, and muscle. These results suggest that BAC induces mitochondrial biogenesis in mice through activating AMPK signaling cascade. BAC may have the potential to be developed as a novel remedy for some diseases associated with mitochondrial dysfunction.

中文翻译：

Benzoylaconine 通过激活 AMPK 信号级联反应诱导小鼠线粒体生物发生。

中药“附子”（附子）及其三种代表性生物碱乌头碱（AC）、苯甲酰乌头碱（BAC）和乌头碱已被证明可以增加线粒体质量。附子是否对线粒体生物发生有影响及其潜在机制尚不清楚。在本研究中，我们专注于 BAC 对线粒体生物发生的影响及其潜在机制。我们证明附子提取物及其三种成分 AC、BAC 和乌头碱在 50 μM 的浓度下显着增加了 HepG2 细胞中的线粒体质量。BAC（25、50、75 μM）剂量依赖性地促进线粒体质量、mtDNA 拷贝数、细胞 ATP 产生以及与 HepG2 细胞中氧化磷酸化 (OXPHOS) 复合物相关的蛋白质的表达。而且，BAC 剂量依赖性地增加参与 AMPK 信号级联的蛋白质的表达；阻断 AMPK 信号消除了 BAC 诱导的线粒体生物发生。我们进一步揭示了 BAC 处理增加了 HepG2 细胞的细胞活力，但没有增加细胞增殖。这些体外结果在用 BAC（每天 10 毫克/千克，腹腔注射）治疗 7 天的小鼠中得到验证。我们发现 BAC 给药增加了小鼠的耗氧率，但对肩胛内温度没有显着影响。同时，BAC 给药增加了 mtDNA 拷贝数和 OXPHOS 相关蛋白的表达，并激活了心脏、肝脏和肌肉中的 AMPK 信号。这些结果表明 BAC 通过激活 AMPK 信号级联反应诱导小鼠线粒体生物发生。

更新日期：2019-01-26

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