Microcalorimetric investigation of six alkaloids from Radix Aconite Lateralis Preparata (Fuzi) on the metabolic activity of mitochondria isolated from rat liver
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Using the TAM air isothermal microcalorimeter, the thermogenic power–time (HP–time) curves of isolated mitochondrial energy metabolism were measured, and the effects of six alkaloids from Radix Aconite Lateralis Preparata (Fuzi) including mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, and benzoylhypaconine on mitochondrial energy metabolism were investigated. Some quantitative information, such as k, P max, T max, Q, P av, and T lag, was obtained from the HP–time curves. The results revealed that mesaconitine, aconitine, and hypaconitine had inhibitory effect on rat-isolated mitochondrial energy metabolism, and their IC50 value was 1.82, 2.22, and 2.48 μg mL−1, respectively, while benzoylmesaconine, benzoylaconine, and benzoylhypaconine promoted mitochondrial energy metabolism, and their EC50 value was 30.95, 14.36, and more than 30 μg mL−1, respectively. Further structure–activity relationship analysis showed that the ester bond in C(8) position, hydroxyl in C(3) position, and ethyl in N atom could significantly influence the energy metabolism. These results provide scientific basis for the treatment of mitochondrial abnormalities and energy dysfunction diseases using Fuzi, and it will be of great interest to doctors and pharmacists.
KeywordsRadix Aconite Lateralis Preparata (Fuzi) Mitochondria Microcalorimetry Energy metabolism Diester diterpenoid alkaloids Monoester diterpenoid alkaloids
We are grateful to the support of National Nature Science Fund (Nos. 81274026, 81403115, 81573631). We thank the reviewers for their critical comments on the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declared no conflict of interest.
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