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Diterpenoid alkaloids with remarkable chemical properties and biological activities are frequently found in plants of the genera Aconitum, Delphinium, and Garrya. Accordingly, several diterpenoid alkaloid constituents of Aconitum and Delphinium plants as well as their derivatives exhibited cytotoxic activity against lung, prostate, nasopharyngeal, and vincristine-resistant nasopharyngeal cancer cell lines. Four new C19-diterpenoid alkaloids, 14-anisoyllasianine (1), 14-anisoyl-N-deethylaconine (2), N-deethylaljesaconitine A (3), and N-deethylnevadensine (4), together with 17 known C19- and C20-diterpenoid alkaloids, were isolated in a phytochemical investigation of rhizoma of Aconitum japonicum Thunb. subsp. subcuneatum (Nakai) Kadota. Their structures were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS). Eight known diterpenoid alkaloids, lipoaconitine, lipomesaconitine, aconine, nevadenine, talatisamine, nevadensine, ryosenamine, and dehydrolucidusculine, were isolated the first time from A. japonicum subsp. subcuneatum. Three of the new C19-diterpenoid alkaloids (1, 3, 4) and six of the known diterpenoid alkaloids were evaluated for cytotoxic activity against five human tumor cell lines.

We explored new cytotoxic C(19)-diterpenoid alkaloid, lipojesaconitine (1), from rhizoma of Aconitum japonicum Thunb. subsp. subcuneatum (Nakai) Kadota. Two additional non-cytotoxic new C(19)-diterpenoid alkaloids, 10-hydroxychasmanine (2) and 3-hydroxykaracoline (3), together with eight known C(19)- and C(20)-diterpenoid alkaloids (4−11) were also isolated. Their structures were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS). Six known diterpenoid alkaloids, foresticine (5), neolinine (6), aconicarchamine A (7), 9-hydroxynominine (8), kobusine (9), and torokonine (10), were isolated for the first time from A. japonicum subsp. subcuneatum. Alkaloid 1 showed cytotoxicity with IC(50) values ranging from 6.0 to 7.3 µM against four human tumor cell lines, except a multidrug-resistant subline, suggesting that 1 was likely exported by P-glycoprotein.

The aconite tuber, which is processed from the roots of a flowering plant commonly known as monkshood, is used clinically for its analgesic, thermal, metabolic, cardiac, and diuretic effects [1]. The aconite tuber contains diterpenoid alkaloids, including aconitine, mesaconitine, hypaconitine, and jesaconitine, and mesaconitine plays a central role in the analgesic effects of this tuber [2]. Powdered aconite root is subjected to toxicity-reducing procedures that are collectively termed “processing.” It is believed that Aconitum alkaloids cannot be detected in the serum of patients who receive Chinese herbal medicines containing processed aconite root [3e6]. Previously, we developed a method to detect four types of Aconitum alkaloids in cases of aconitine poisoning, by using liquid chromatography-mass spectrometry (LC-MS) techniques, and we applied this method in a clinical setting [7e9]. Benzoylaconine, benzoylmesaconine, benzoylhypaconine, and 14-anisoylaconine are formed at the C-8 site during the toxicityreducing process following acetylic hydrolysis of Aconitum alkaloids. We previously detected four types of Aconitum alkaloids, aconitine, mesaconitine, hypaconitine, and jesaconitine, in healthy adult volunteers who were administered powdered processed aconite root containing Aconitum carmichaeli Debeaux and Aconitum japonicum Thunberg mixed at a fixed ratio [10]. Several pharmaceutical companies produce their own powdered processed aconite root products that may contain different varieties of aconite

The flower in Aconitum has five violet sepals. Its morphology is unique and thought to be adapted for pollination by bumblebees. To assess the adaptive significance of Aconitum flower morphology, we examined the function of the five sepals in bumblebee-pollination. We manipulated the flower by removing the sepals and then observed and measured bumblebee pollination efficiency in a single visit. Bumblebee behavior differed somewhat on the manipulated flowers. Manipulation of the two lower sepals led to a pollination efficiency that was the same as no manipulation. Pollination efficiency was lowered significantly after lateral sepal manipulation, and this was caused by the absence of the arch structure normally formed by two lateral sepals changing the posture of the pollinator. Therefore, it was postulated that the arch structure formed by the lateral sepals functions to ensure correct pollination.

Processed Bushi powder for ethical dispensing, called TJ-3022, is a herbal drug of processed Aconiti tuber (Aconitum carmichaeli Debeaux) and TJ-3023 is newly developed to contain a higher proportion of diester alkaloid of aconitine (Aconitum carmichaeli Debeaux and Aconitum japonicum Thunberg). Safety of TJ-3022 and TJ-3023 was evaluated by measuring the level of aconitum alkaloids in healthy adult volunteers. Forty subjects were assigned to one of two groups (each 20 subjects): TJ-3022 group or TJ-3023 group. The subjects received the powdered processed Aconiti tuber 3 g/day and the blood concentrations of aconitum alkaloids were measured at 90 min and 72 h after taking the study drug. The serum concentrations of aconitum alkaloids after 90 min and 72 h in the TJ-3023 group were higher than those in the TJ-3022 group. As for the chronological changes in the serum concentration, a significant decrease was observed in the TJ-3022 group, while no significant decrease was seen in the TJ-3023 group, which suggests that an analgesic effect in TJ-3023 was stronger than in TJ-3022. Aconitum alkaloids, which always have been believed to have the blood concentration below the measurement limit in human, were detected for the first time, although the detected amounts were minute. The results suggest that TJ-3023 shows sufficient analgesic effect with smaller dose than TJ-3022.

The extract of an Oriental medicine "bushi", Aconitum japonicum roots (raw), was fractionated monitored by the analgesic activity in the tail pressure test, leading to the isolation of a mixture of the aconitines but no other constituents as the active principles. The aconitines have been compared in a variety of animal tests for analgesic activity. As the results, the alkaloids have proved in the tail pressure method and the acetic acid-induced writhing method to show analgesic activity in decreasing order : mesaconitine > aconitine > hypaconitine, though they exhibited no significant activity in the hot plate method. Heating of the raw Aconitum roots at 100°, which is one of the processing procedures of the crude drug, has brought about a rapid decrease of the analgesic activity with concomitant decrease of the content of the aconitines, demonstrating that the benzoylaconines produced by hydrolysis of the aconitines showed little or no analgesic activity. Assay of the benzoylaconines has revealed a weak analgesic activity in the acetic acid-induced writhing test. On the basis of the present results, it is predicted that the clinical effectiveness of the crude drug is due to the aconitines (especially mesaconitine) and partly to the benzoylaconines.

The structure of two new diterpene alkaloids, 3-epi-ignavinol (1) and 2, 3-dehydrodelcosine (3), isolated from (Aconitum)___- (japonicum)___- var. (montanum)___- Nakai collected at Mt. Arafune, were elucidated.

The structure and absolute configuration of sadosine, a new C20-diterpene alkaloid isolated from Aconitum japonicum Thunb., have been determined by X-ray crystallography of sadosine and its methiodide.

Two new diterpenoid alkaloids, subcumine and subcusine, were isolated from the roots of Aconitum japonicum Thunb. The structures of these alkaloids were determined on the basis of spectral data, chemical evidence, and X-ray analysis. We also have isolated two known alkaloids, ezochasmaconitine and anisoezochasmaconitine