Article

Benzoylaconine induces mitochondrial biogenesis in mice via activating AMPK signaling cascade

Authors: Xiao-hong Deng1,2, Jing-jing Liu1,2, Xian-jun Sun1,2, Jing-cheng Dong1,2, Jian-hua Huang1,2
1 Department of Integrative Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
2 Academy of Integrative Medicine, Fudan University, Shanghai 200040, China
Correspondence to: Jing-cheng Dong: jcdong2004@126.com, Jian-hua Huang: hjhzyj@aliyun.com,
DOI: 10.1038/s41401-018-0174-8
Received: 5 May 2018
Accepted: 16 September 2018
Advance online: 12 October 2018

Abstract

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.
Keywords: benzoylaconine; Aconiti Lateralis Radix; traditional Chinese medicine; mitochondrial biogenesis; AMP-activated protein kinase; compound C

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