[show abstract][hide abstract] ABSTRACT: Annonaceous acetogenins (ACGs) are one of the most interesting classes of natural products appearing in the past two decades. Here, we studied the antitumor activity and toxicity relationship of ACGs including annosquamin B (1), bullatacin (2) and annosquatin B (3) in vivo. A single intraperitoneal (i.p.) injection of 100 μg/kg of annosquamin B, bullatacin and annosquatin B did not cause side effects in normal mice. Bullatacin treatment with five doses of 25 and 50 μg/kg in H22 hepatoma cells bearing mice resulted in about 61% reduction in tumor growth with hematologic parameters increased significantly in normal mice. Annosquamin B and annosquatin B treatments with 10 doses of 25, 50 and 100 μg/kg in the H22 hepatoma cells transplantation tumor model mice resulted in maximum 53.7% and 58.7% reduction in tumor growth, respectively, and did not cause severe side effects in normal mice. This study provided the evidence that adjacent bis-THF ACGs showed higher antitumor activity and toxicity than mono-THF and nonadjacent bis-THF ACGs in vivo. Furthermore, it was found that bullatacin led to liver and kidney toxicity via increasing calcium concentration, ROS production, and Bax expression and Bax/Bcl-2 ratio in rats with repeated treatment with bullatacin for three weeks.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 05/2013; · 2.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: Custard apple (Annona squamosa L.) is an edible tropical fruit, and its seeds had been used in south China as a folk medicine to treat "malignant sore" (cancer) and as an insecticide. Phytochemical investigation of the ethanol fraction of custard apple seeds led to the isolation of six new annonaceous acetogenins: annosquacins A-D (1-4), annosquatin A (5) and annosquatin B (6). Their structures were elucidated by spectroscopic analysis. Compounds 1-4 are adjacent bistetrahydrofuran annonaceous acetogenins. Compounds 5 and 6 are non-adjacent bistetrahydrofuran annonaceous acetogenins and the first examples in which the tetrahydrofuran ring system is located between C-9 and C-20. The absolute configurations of 1-6 were defined by the application of the Mosher method. Compounds 1-6 exhibited potent cytotoxic activity in vitro against five human tumour cell lines. Compounds 5 and 6 showed a high selectivity toward the MCF-7 and A-549 cell line respectively.
[show abstract][hide abstract] ABSTRACT: To identify the differences in characteristics of raw oyster and oysters calcined under different temperatures.
Identified raw oyster, oysters calcined under different temperatures and calcium carbonate, calcium oxide by differential thermal analysis, infrared spectroscopy and X-ray diffraction analysis.
Composition of calcined oysters was closer to calcium carbonate than raw oyster.
The fingerprints are established and identify raw oyster and calcined oysters.
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 10/2012; 35(10):1590-4.
[show abstract][hide abstract] ABSTRACT: Seeds of Annona squamosa L. have been used in the south of China as a folk remedy to treat "malignant sores" (cancer).
To investigate the chemical constituents and the anti-tumor activity of the standardized A. squamosa seeds extract in vitro and in vivo.
Annonaceous acetogenin profiles of the standardized extract were determined by using Fourier transform infrared (FT-IR) and high performance liquid chromatography (HPLC) techniques. The anti-tumor activity of the extract was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity in vitro and H(22) hepatoma cells transplantation tumor model in vivo.
The FT-IR spectroscopy showed the presence of annonaceous acetogenin compounds in the extract. Two major annonaceous acetogenins: 12, 15-cis-squamostatin-A and bullatacin were identified and quantified by HPLC. The seed extract showed significant anti-tumor activity against four human tumor cell lines, especially for MCF-7 (IC(50). 0.25 μg/ml) and Hep G2 (IC(50). 0.36 μg/ml) cells in vitro. The extract inhibited the growth of H(22) tumor cells in mice with a maximum inhibitory rate of 69.55% by oral administration.
A. squamosa seed extract showed significant anti-tumor activities against human hepatoma cells in vitro and in vivo, indicating a potential for developing the extract as a novel anti-liver cancer drug.
Journal of ethnopharmacology 05/2012; 142(2):462-6. · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: a b s t r a c t Annonaceous acetogenins (ACGs), as one of the most powerful groups of mitochondrial complex I inhib-itors, exhibit potent cytotoxic activity against a variety of human tumor cell lines. In this study, the anti-tumor activities of three main types of ACGs were investigated using S180 and HepS xenografts bearing mice simultaneously. The results revealed that select ACGs suppressed tumor growth in a dose-depen-dent fashion. Tested ACGs showed more selective antitumor activity against HepS. Furthermore, adjacent bis-THF ACGs were more active than mono-THF and nonadjacent bis-THF ACGs against HepS and S180; nonadjacent bis-THF ACGs were more active than mono-THF ACGs against S180, but mono-THF ACGs were more potent than nonadjacent bis-THF ACGs against HepS. Annonaceous acetogenins (ACGs) constitute a series of natural products isolated exclusively from Annonaceae species, which show significant cytotoxicity to human cancer cell lines in vitro. 1–6 They are a unique class of C 35 or C 37 secondary metabolites derived from the polyketide pathway. 7,8 The mitochondrial complex I (NADH: ubiquinone oxidoreductase) of the respiratory chain was identified as the target enzyme for ACGs, 9,10 which architecture has been resolved recently. 11 ACGs were characterized as one of the most powerful groups of complex inhibitors. 10 According to the number and location of the tetrahydrofuran (THF) along the hydrocarbon chain, ACGs could be classified into three main types: mono-THF, adjacent bis-THF and nonadjacent bis-THF. In vitro studies, the adjacent bis-THF ACGs are the most potent compounds among this family, and the nonadjacent bis-THF ACGs are, in general but not always, superior to the mono-THF ACGs, which, in turn, are more potent than non-THF ACGs. They have also been shown to overcome resistance in multidrug resistant (MDR) tumors. 12 In our prior study, a series of annonaceous acetogenins (ACGs) were isolated from the seeds of Annona squamosa Linn. and some of these compounds exhibited potent cytotoxic activity against a variety of human tumor cell lines. 13 Concentration-response pro-files on panels of human cancer cell lines grown and treated in a monolayer or as a suspension had been proven useful in selecting cytotoxic compounds for further studies. However, experiments with cells in monolayer or suspension do not provide sufficient Figure 1. Structures of ACGs 1–5 used for study.
[show abstract][hide abstract] ABSTRACT: A liquid chromatography-mass spectrometry method has been developed and validated for the quantification of bullatacin, a bistetrahydrofuran annonaceous acetogenin, in rat plasma. Squamostatin-A was selected as the internal standard. Analytes were extracted from rat plasma by liquid/liquid extraction using ethyl acetate with high efficiency. The chromatographical separation was performed on an Agilent Zorbax SB-C₁₈ column (150 mm × 2.1 mm, 5 μm). The mobile phase consisted of methanol and deionized water (95:5, v/v) containing 0.01% (v/v) formic acid. The chromatographic run time was 7 min per injection and flow rate was 0.2 mL/min. The retention time was 3.22 and 5.23 min for internal standard and bullatacin, respectively. The elutes were detected under positive electrospray ionization and the target analytes quantified by selected ion monitoring mode (645.9 m/z for bullatacin and 661.9 m/z for squamostatin-A). The method was sensitive with the limit of quantitation at 0.5 ng/mL in 100 μL of rat plasma. Good linearity (r²=0.9998) was obtained covering the concentration of 0.5-2000 ng/mL. The intra- and inter-day assay precision ranged from 3.2 to 8.7% and 2.7 to 9.2%, respectively. In addition, the stability, extraction recovery and matrix effect involved in the method were also validated. This method was applied to measure the plasma bullatacin concentrations after a single tail vein intravenous administration of bullatacin in rats.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 04/2012; 897:94-7. · 2.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Annonaceous acetogenins (ACGs), as one of the most powerful groups of mitochondrial complex I inhibitors, exhibit potent cytotoxic activity against a variety of human tumor cell lines. In this study, the antitumor activities of three main types of ACGs were investigated using S180 and HepS xenografts bearing mice simultaneously. The results revealed that select ACGs suppressed tumor growth in a dose-dependent fashion. Tested ACGs showed more selective antitumor activity against HepS. Furthermore, adjacent bis-THF ACGs were more active than mono-THF and nonadjacent bis-THF ACGs against HepS and S180; nonadjacent bis-THF ACGs were more active than mono-THF ACGs against S180, but mono-THF ACGs were more potent than nonadjacent bis-THF ACGs against HepS.
[show abstract][hide abstract] ABSTRACT: Three new monotetrahydrofuran annonaceous acetogenins, Annosquamins A–C (1–3) were isolated from the 95% EtOH extract of Annona squamosa seeds, in addition to the known compounds, solamin, annotemoyin-1, uvariamicin-II, uvariamicin-III. Their structures were elucidated by spectroscopic analysis and the relative configurations of bearing tetrahydrofuran rings were established by comparing NMR data with model compounds.
[show abstract][hide abstract] ABSTRACT: Annonaceous acetogenins are characterized by special chemical structures and antitumor mechanism. In this paper, the advance in structure activity relationship of natural annonaceous acetogenins is reviewed.
Chinese Journal of Organic Chemistry 01/2012; 32:966-972. · 0.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: A rapid, sensitive and specific method using liquid chromatography with tandem mass spectrometric detection (LC-MS) was developed for the analysis of sauchinone in rat plasma. Di-O-methyltetrahydrofuriguaiacin B was used as internal standard (IS). Analytes were extracted from rat plasma by liquid-liquid extraction using ethyl acetate. A 2.1 mm i.d. × 150 mm, 5 µm, Agilent Zorbax SB-C(18) column was used to perform the chromatographic analysis. The mobile phase was methanol-deionized water (80:20, v/v). The chromatographic run time was 7 min per injection and the flow-rate was 0.2 mL/min. The tandem mass spectrometric detection mode was achieved with electrospray ionization interface in positive-ion mode (ESI(+) ). The m/z ratios [M + Na](+) , m/z 379.4 for sauchinone and m/z 395.4 for IS were recorded simultaneously. Calibration curve were linear over the range of 0.01-5 µg/mL. The lowest limit of quantification was 0.01 µg/mL. The intra-day and inter-day precision and accuracy of the quality control samples were 2.94-9.42% and 95.79-108.05%, respectively. The matrix effect was 64.20-67.34% and the extraction recovery was 93.28-95.98%. This method was simple and sensitive enough to be used in pharmacokinetic research for determination of sauchinone in rat plasma.
[show abstract][hide abstract] ABSTRACT: Three new bistetrahydrofuran annonaceous acetogenins (1-3) were isolated from a 95% EtOH extract of Annona squamosa seeds. Four known annonaceous acetogenins, uvarigrandin A (4), bullatacin (5), squamostatin-A (6), and squamostatin-D (7), were also isolated. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of the carbinol centers of 1-3 were defined by application of the Mosher method. These compounds all exhibited significant cytotoxic activity in vitro against five human tumor cell lines.
Journal of Natural Products 11/2011; 74(11):2477-81. · 3.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: A high performance liquid chromatography method coupled with diode array detection (HPLC-DAD) was developed for simultaneous determination of five major active flavonoids, two aristolactams and four main lignans in Saururus chinensis, namely rutin (1), isoquercitrin (2), quercetin-3-O-beta-d-glucopyranosyl (1-->4)-alpha-l-rhamnoside (3), quercitrin (4), quercetin (5), aristolactam A II (6), sauristolactam (7), dihydroguaiaretic acid (8), sauchinone (9), licarin A (10) and licarin B (11). The analysis was performed on an Agilent Eclipse XDB C(18) column (4.6mmx150mm, 5microm) with gradient elution of 0.4% aqueous phosphoric acid and acetonitrile. The detection wavelengths were 280 and 360nm. All calibration curves showed good linearity (r(2)>0.9991) within test ranges. The method was reproducible with intra- and inter-day variation less than 3.2%. The recovery of the assay was in the range of 95.1-103.9%. The validated method was successfully applied for the analysis of the eleven bioactive compounds in seven samples from different harvesting seasons and significant variations were revealed. The results indicated that the developed method can be used as a suitable quality control method for S. chinensis and it should be harvested in August (fruiting period) for Jiangsu cultivation regions, taking the yield into consideration, with the highest amounts of lignans, relative higher amounts of flavonoids and lower amounts of aristolactams.
Journal of pharmaceutical and biomedical analysis 11/2009; 51(5):1142-6. · 2.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Two new sphingolipids were isolated from the 95% EtOH extract of traditional Chinese medicinal plant Isatis indigotica. Their structures were elucidated as (2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(1) and 1-O-beta-D-glucopyranosyl-(2S,3R)-3-hydroxymethyl-N-(2'-hydroxynonacosanoyl)-trideca-9E-sphingenine(2) on the basis of spectroscopic data. Their cytotoxic effects were evaluated by using MTT method.
[show abstract][hide abstract] ABSTRACT: To study the chemical constituents from water extract of Radix isatidis. (Isatis indigotica Fort. ).
The water extract was underwent absorption by D101 macroporous resin, the portion eluted by ethanol of different concentrations was isolated and purified on silica gel column repeatedly. The obtained compounds were identified and structurally elucidated by their physico-chemical properties and spectral analysis.
Five compounds were isolated from water extract of Radix isatidis, and were partly identified separately: 3-[2'-(5'-hydroxymethyl) furyl] -1 (2H) -isoquinolinone-7-O-beta-D-glucoside (I), lariciresinol-4,4'-di-O-beta-D-glucopyranoside (II), lariciresinol-4-O-beta-D-glucopyranoside (III), 2-hydroxy-1, 4-benzenedicarboxylic acid (IV), mannitol (V).
Compound I is a new compound and compounds IV and V were isolated from the plant for the first time.
Yao xue xue bao = Acta pharmaceutica Sinica 01/2007; 41(12):1193-6.