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Bioassay-guided fractionation of an n-BuOH extract of the lateral roots of Aconitum carmichaeli DEBX. led to the isolation of 5 cardioactive C 19 -diterpenoid alkaloids: N-deethylaconine (1), beiwutinine (2), hypaconine (3), mesaconine (4), and 15α-hydroxyneoline (5). N-Deethylaconine and beiwutinine are new aconitinetype C 19 -diterpenoid alkaloids. Hypaconine was isolated from this species for the first time. Among them, mesaconine, hypaconine, and beiwutinine showed the strongest cardiac actions on the isolated perfused bullfrog heart. Furthermore, mesaconine has protective effects, including improved inotropic effect and left ventricular diastolic function, on myocardial ischemia-reperfusion injury in rat at a dose of 10 −9 mol/L. However, mesaconine has almost no effect on heart rate.

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Salvianolic acid A (SalA) is one of the main active constituents in Salvia miltiorrhiza (Danshen). Although the pharmacokinetics of SalA in rats after intravenous (i.v.) administration of Danshen injection has been reported, the information relevant to the metabolites of SalA in vivo is absent so far. In this study, by means of liquid chromatography with time-of-flight mass spectrometry (LC/TOFMS) and liquid chromatography with ion trap mass spectrometry (LC/MS(n)) techniques, the unknown metabolites of SalA in rat plasma after i.v. administration of the purified SalA at the dose of 20 mg/kg body weight were identified. A liquid-liquid extraction method was established to separate the metabolites from the plasma and the chromatographic separations were performed on a Xterra MS C(18) column (100 mm x 4.6 mm i.d., 3.5 microm) with acetonitrile/methanol/water/formic acid (20.5:19.5:64: 0.05, v/v/v/v) as the mobile phase at a constant flow rate of 0.2 mL/min. Based on the data obtained from the LC/TOFMS determination (the total ion chromatograms, MS spectra and extracted ion chromatograms), in combination with the characteristic fragment ions acquired from the LC/MS(n) determination, five metabolites were identified as SalA-monoglucuronide, monomethyl-SalA-monoglucuronide, mono-methyl-SalA, dimethyl-SalA and dimethyl-SalA-monoglucuronide, and the possible chemical structures were deduced. The results indicated that SalA might mainly undergo two metabolic pathways in vivo in rats, which were methylation and glucuronidation. The present studies have laid a solid foundation for the metabolic mechanism of SalA in vivo.

Thirty three C 19-diterpenoid alkaloids, twenty-two prepared from known C 19-diterpenoid alkaloids and eleven isolated from Aconitum and Delphinium spp. were evaluated for their cardiac activity in the isolated bullfrog heart assay. Among them, eleven compounds exhibited cardiac activity, with average rate of amplitude increase in the range of 16-118%. Compound 7, mesaconine (17), hypaconine (25), and beiwutinine (26) exhibited strong cardiac activities relative to the reference drug. The structure-activity relationship data acquired indicated that an -hydroxyl group at C-15, a hydroxyl group at C-8, an -methoxyl or hydroxyl group at C-1, and a secondary amine or N-methyl group in ring A are important structure features necessary for the cardiac activities of the aconitinetype C 19-diterpenoid alkaloids without any ester groups. In addition, an -hydroxyl group at C-3 is also helpful for the cardiac activity of these alkaloids.