Effects of Alkaloids from Aconitum yesoense var. macroyesoense on Cutaneous Blood Flow in Mice.

Abstract

Nine alkaloid constituents in the root of Aconitum yesoense var. macroyesoense, as well as three acetylated derivatives, were examined for their peripheral vaso-activities by measuring laser-flowmetrically the cutaneous blood flow in the hind foot of mice after intravenous administration. The major constitutive delcosine (1), 14-acetyldelcosine (2) and lucidusculine (3), respectively, had little or very mild vaso-activity. Kobusine (4) and pseudokobusine (5) and three minor constituents, luciculine (6), 1-acetylluciculine (7) and dehydroluciculine (8), together exhibited a rapid increase in blood flow reaching a peak with a magnitude almost equal to that produced by hydralazine, when administered intravenously at the same dosage level of 20 mg/kg. Among them, 4 was characterized by successive reversal of the increase to a decrease in blood flow, while 7 produced a flow with a more delayed peak time. Dehydrolucidusculine (9) exhibited a transient decrease in blood flow prior to occurrence of the increase, as did papaverine. Consequently, it is assumed that the alkaloids, especially those of the C20-diterpenoid type, in the root of this Aconitum plant have peripherally vaso-dilating activities to varying degrees in mice, probably due to their direct action on the cutaneous microvasculature in a similar fashion to that shown by hydralazine. The laser blood flowmetric method would be useful as an in vivo means of qualitative as well as quantitative screening of chemically modified derivatives of peripherally vasoactive agents in mice.

Structure–activity relationships and the cytotoxic effects of novel diterpenoid alkaloid derivatives against A549 human lung carcinoma cells

“…Kobusine ( 1 ) and pseudokobusine ( 2 ), the major alkaloid constituents of Aconitum yesoense var. macroyesoense , and certain semi-synthetic derivatives of diterpenoid alkaloids have been shown by using a Doppler-type laser blood flow meter to significantly increase cutaneous blood flow in the hind feet of anaesthetized mice [5–7]. …”

Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth

“…Furthermore, as shown Fig. 3, the activity of atisine type compounds including compound 35 (17,18,36, 37 and 38) seems to change greatly with the cells. Although the preliminary experiments showed no radiosensitizing effect on Hela and Raji by compound 35 (date not shown), compound 35 showed a radiosensitizing effect before or after X irradiation on A549.…”

“…Furthermore, there is little information about the pharmacological properties of C 20 -diterpenoid alkaloids which show low toxicities. In previous reports, we have reported that Aconitum C 20 -diterpenoid alkaloids and their novel derivatives showed an increased cutaneous blood flow [15][16][17]. Very recently, we found that some novel derivatives derived from C 20 -diterpenoid alkaloids suppress the growth of human tumor cell lines (unpublished data).…”

“…Surprisingly, although the suppressive effects by each compound depend on the cell lines, all of compounds17,18,35, 36, 38 and 39 that demonstrated anti-proliferative activities in all cell lines are novel derivative compounds that have the C 20 -diterupenoid atisine type structure. Furthermore, all of compounds that showed anti-proliferative activities to one of cell lines are also novel compounds derived from C 20 -diterupenoid alkaloids (compound15, 16, 20, 21, 25, 26, 32 and 33).…”

Cytotoxic Effects of Diterpenoid Alkaloids Against Human Cancer Cells

“…Pacific Giant [35] (Figure 3). The remaining tested C 19 -diterpenoid alkaloids from this subtype were synthetic alkaloids, N -deethyldelsoline ( 29 ) [18], 1-acetyldelcosine ( 34-1 ) [36], 1,14-diacetyldelcosine ( 34-2 ) [37], 1-(4-trifluoromethylbenzoyl)delcosine ( 34-24 ) [30], delsoline ( 34-42 ) [37], 1,14-di-(4-nitrobenzoyl)-delcosine ( 34-45 ) [30], 14-acetyl-1-(4-nitrobenzoyl)delcosine ( 34-46 ) [30], and 1-acyl or 1,14-diacyldelcosine derivatives ( 34-3 ~ 34-23 , 34-25 ~ 34-41 , 34-44 , and 34-47 ) [38], prepared from delcosine ( 34 ) or delsoline ( 34-42 ) (Figure 3). These 42 C 19 -diterpenoid alkaloids were evaluated for antiproliferative activity against four to five human tumor cell lines (A549, DU145, MDA-MB-231, MCF-7, KB, and KB-VIN) [30,38] (Table 2).…”