Isoverticine

Planta Med. 2016 Feb;82(3):195-204.

Characterization of the Isosteroidal Alkaloid Chuanbeinone from Bulbus of Fritillaria pallidiflora as Novel Antitumor Agent In Vitro and In Vivo.[Pubmed: 26584458]

Bulbus of Fritillaria pallidiflora, the dried bulb of F. pallidiflora, is widely used in Chinese folk medicine due to its powerful biological activities. The aim of this study was to investigate in vitro and in vivo antitumor activity of different fractions and isosteroidal alkaloids from bulbus of F. pallidiflora and clarify its putative mechanism of antitumor activity.
METHODS AND RESULTS:
Firstly, we assayed in vitro antitumor effects of different fractions from bulbus of F. pallidiflora and found that chloroform extracts and purified total alkaloids of bulbus of F. pallidiflora showed higher cytotoxic activity than other tested extracts. We further isolated four main alkaloids, chuanbeinone, imperialine-β-N-oxide, Isoverticine and Isoverticine-β-N-oxide, from the total alkaloids of bulbus of F. pallidiflora and found that they display significant cytotoxicity, whereby chuanbeinone showed the highest activity against Lewis lung carcinoma cells. Moreover, we found that chuanbeinone induced S phase arrest and further increased apoptosis of Lewis lung carcinoma cells. The results of Western blotting experiments showed that the expression of the antiapoptotic Bcl-2 was reduced by chuanbeinone treatment, while the proapoptotic protein Bax and caspase-3 were increased. Moreover, we investigated the in vivo antitumor activity of chuanbeinone and characterized its putative antitumor mechanism of action by the TUNEL assay and by histological and immunohistochemical analyses.
CONCLUSIONS:
Our results showed that chuanbeinone exhibited significant antitumor activity in vivo, while notably inhibiting tumor angiogenesis and inducing apoptosis characterized by an increased expression of caspase-3. Our findings show that chuanbeinone exhibits significant antitumor activity in vitro and in vivo, and points to possible therapeutic potential for this compound as well as for its natural source, bulbus of F. pallidiflora.

J Ethnopharmacol. 2012 Jan 6;139(1):189-93.

Antitussive, expectorant and anti-inflammatory activities of four alkaloids isolated from Bulbus of Fritillaria wabuensis.[Pubmed: 22101082 ]

Bulbus Fritillaria Cirrhosae (BFC), known by the Chinese name "Chuan-Bei-Mu", is used as an antitussive, antiasthmatic and expectorant drug for more than 2000 years in China, and Bulbus of Fritillaria wabuensis S. Y. Tang & S. C. Yueh (BFW) was recorded in the 2010 edition of China Pharmacopoeia as one of sources for BFC. The primary objective of this study was to evaluate the antitussive, expectorant and anti-inflammatory effects of alkaloids - imperialine, imperialine-β-N-oxide, Isoverticine, and Isoverticine-β-N-oxide, which were isolated from BFW, and to provide experimental evidence for its traditional use.
METHODS AND RESULTS:
The alkaloids were isolated using phytochemical methods, and their structures were determined by spectroscopic analysis. Their antitussive effects were measured using murine model of ammonia induced cough, the expectorant effects were evaluated by measuring mice's tracheal phenol red output, and the anti-inflammatory effects were assessed by using the murine model of xylene induced ear edema. The structures of the four alkaloids - imperialine, imperialine-β-N-oxide, Isoverticine, and Isoverticine-β-N-oxide isolated from BFW were confirmed. The four alkaloids significantly inhibited cough frequency and increased latent period of cough in mice induced by ammonia. Imperialine and Isoverticine showed obviously antitussive activities in a dose-dependent manner. Besides, the four alkaloids markedly enhanced mice's tracheal phenol red output in expectorant assessment and significantly inhibited the development of ear edema in anti-inflammatory evaluation assay. Moreover, significant differences were found between the structure-activity relationships of the four alkaloids.
CONCLUSIONS:
The four alkaloids exhibited significant antitussive, expectorant and anti-inflammatory activities. We suggest that they may be the active ingredients of BFW. The results of the present study provided evidence for BFW to be used as an antitussive and expectorant Traditional Chinese Medicine (TCM).