The in Vitro and in Vivo Antitumor Activities of Tetracyclic Triterpenoids Compounds Actein and 26-Deoxyactein Isolated from Rhizome of Cimicifuga foetida L.

AIMS: This work aims to study the in vitro and in vivo antitumor activities of tetracyclic triterpenoids compounds actein and 26-deoxyactein. Further, the mechanism is investigated. METHODS: In vitro, a modified MTT method was used to assay the cytotoxicities of actein and 26-deoxyactein in 12 human tumor cell lines. In vivo, mouse sarcoma S180 and human lung cancer A549 cells were respectively implanted subcutaneously in ICR mice and nude mice to establish implanted tumor models. Flow cytometry (FCM) was used to assay the cycle distribution of the tumor cells. Immunohistochemistry was used to measure CD31-positive expression in the xenogrft tumor by analyzing microvessel density (MVD). In addition, acute toxicities of actein and 26-deoxyactein were also evaluated. RESULTS: Actein and 26-deoxyactein inhibited the proliferation of the 12 human cancer cell lines tested with the values of 50% inhibitory concentrations (IC50) between 12.29 and 88.39 µg/mL. In vivo, both actein (3-27 mg/kg) and 26-deoxyactein (3-27 mg/kg) significantly inhibited the growth of the implanted sarcoma S180 in a dose-dependent manner. Actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) markedly inhibited the xenograft growth with T/C (%) values of 38%, 55% for actein, and 35%, 49% for 26-deoxyactein. Compared with the vehicle control, actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) significantly reduced the MVD in the xenograft tumor. The FCM result showed that human leukemia HL-60 cells were arrested at G1 phase after treated with either actein (6.25-25 µg/mL) or 26-deoxyactein (6.25-25 µg/mL) for 48 h. A limited trial in mice showed that both of the minimal lethal doses (MLDs) of actein and 26-deoxyactein were over 5 g/kg. CONCLUSIONS: Both actein and 26-deoxyactein have low toxicities. Importantly, both these two tetracyclic triterpenoids compounds isolated from rhizome of Cimicifuga foetida L. have significant antitumor activities in vitro and in vivo, which is associated with cell cycle arrest and angiogenesis inhibition.

[Coumarins from Skimmia arborescens and its anti-inflammatory effect].

To investigate chemical constituents contained in Skimmia arborescens. The chemical constituents were separated by silica gel column chromatography, pharmadex LH-20, RP-C18, and 1H, 13C-NMR spectroscopic analysis were employed for the structural elucidation. Six coumarin compounds were separated from S. arborescens. Their structures were elucidated as umbelliferone (1), scopoletin (2), scopolin (3), nodakenetin (4), skimmin (5), 6, 7-dimethoxycoumarin (6), and all compounds were separated from the plant for the first time. Using the model of ear swelling caused by xylol of mice, the anti-inflammatory effect of its total extract was evaluated. The result indicated that middle and high dose groups of its total extract could obviously inhibit the ear swelling caused by xylol of mice.

New dammarane-type triterpenoid saponins from Panax notoginseng saponins.

BACKGROUND: Panax notoginseng saponin (PNS) is the extraction from the roots and rhizomes of Panax notoginseng (Burk.) F. H. Chen. PNS is the main bioactive component of Xuesaitong, Xueshuantong, and other Chinese patent medicines, which are all bestselling prescriptions in China to treat cardiocerebrovascular diseases. Notoginsenoside R1 and ginsenoside Rg1, Rd, Re, and Rb1 are the principal effective constituents of PNS, but a systematic research on the rare saponin compositions has not been conducted. OBJECTIVE: The objective of this study was to conduct a systematic chemical study on PNS and establish the HPLC fingerprint of PNS to provide scientific evidence in quality control. In addition, the cytotoxicity of the new compounds was tested. METHODS: Pure saponins from PNS were isolated by means of many chromatographic methods, and their structures were determined by extensive analyses of NMR and HR-ESI-MS studies. The fingerprint was established by HPLC-UV method. The cytotoxicity of the compounds was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide assay. RESULTS AND CONCLUSION: Three new triterpenoid saponins (1-3) together with 25 known rare saponins (4-28) were isolated from PNS, except for the five main compounds (notoginsenoside R1 and ginsenoside Rg1, Rd, Re, and Rb1). In addition, the HPLC fingerprint of PNS was established, and the peaks of the isolated compounds were marked. The study of chemical constituents and fingerprint was useful for the quality control of PNS. The study on antitumor activities showed that new Compound 2 exhibited significant inhibitory activity against the tested cell lines.