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.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (grant number 81373791).
Author contribution
XHD and JJL contributed equally to this work; XHD and JHH conceived and designed the study; XHD and JJL preformed the experiments and wrote the manuscript; XJS analyzed the data; and JHH and JCD supervised the project. All authors reviewed and approved the manuscript.
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Deng, Xh., Liu, Jj., Sun, Xj. et al. Benzoylaconine induces mitochondrial biogenesis in mice via activating AMPK signaling cascade. Acta Pharmacol Sin 40, 658–665 (2019). https://doi.org/10.1038/s41401-018-0174-8
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DOI: https://doi.org/10.1038/s41401-018-0174-8
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