METHODS AND RESULTS: We established a qualitative method to analyze the main chemical compositions of the root of Aster tataricus. Most of the peaks were separated on a C(18) column packed with 5.0 μm particles, and 28 compounds were identified, including 11 chlorogenic acids, ten astins/asterinins, and seven astersaponins, four of which were reported for the first time from A. tataricus. Furthermore, we developed a reliable method for the simultaneous quantification of 3-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, astin A, Astin B, astin C, astersaponin A, and astersaponin C, and the qualified separations were achieved only on a C18 column packed with 2.7 μm particles. CONCLUSIONS: The method was used to measure the concentrations of eight components in samples from two major producing areas in China, and the average contents in samples from Bozhou (Anhui) were higher than those in samples from Anguo (Hebei).
METHODS AND RESULTS: Antitumor activities on Sarcoma 180A of a series of cyclic pentapeptides, astins, isolated from the roots of Aster tataricus, were examined. CONCLUSIONS: The activities on various congeners of the dichlorinated proline residues prepared by chemical conversion and a hepatic microsomal biotransformation in rats suggested that 1,2-cis dichlorinated proline residues of astin A, Astin B and astin C play an important role in the antitumor activity of astins. 123914-49-8
We established a qualitative method to analyze the main chemical compositions of the root of Aster tataricus. Most of the peaks were separated on a C(18) column packed with 5.0 mum particles, and 28 compounds were identified, including 11 chlorogenic acids, ten astins/asterinins, and seven astersaponins, four of which were reported for the first time from A. tataricus. Furthermore, we developed a reliable method for the simultaneous quantification of 3-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, astin A, Astin B, astin C, astersaponin A, and astersaponin C, and the qualified separations were achieved only on a C18 column packed with 2.7 mum particles. The method was used to measure the concentrations of eight components in samples from two major producing areas in China, and the average contents in samples from Bozhou (Anhui) were higher than those in samples from Anguo (Hebei).
Astins (including Astin B) are a class of halogenated cyclic pentapeptides isolated from the medicinal herb of Aster tataricus. However, our previous works showed that the herbal medicine was hepatotoxic in vivo, and a toxicity-guided isolation method led to the identification of a cyclopeptide Astin B. Astin B is structurally similar to cyclochlorotine, a well-known hepatotoxic mycotoxin. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of Astin B on human normal liver L-02 cells. We found that Astin B has hepatotoxic effects in vitro and in vivo and that hepatic injury was primarily mediated by apoptosis in a mitochondria/caspase-dependent manner. Astin B provoked oxidative stress-associated inflammation in hepatocytes as evidenced by increased levels of reactive oxygen species (ROS), reduced contents of intracellular glutathione (GSH), and enhanced phosphorylation of c-Jun N-terminal kinase (JNK). Furthermore, the mitochondria-dependent apoptosis was evidenced by the depolarization of the mitochondrial membrane potential, the release of cytochrome c into cytosol, the increased ratio of Bax/Bcl-2, and the increased activities of caspases-9 and -3. Interestingly, Astin B treatment also induces autophagy in L-02 cells, characterized by acidic-vesicle fluorescence, increased LC3-II and decreased p62 expression. Autophagy is a protective mechanism that is used to protect cells from apoptosis. The presence of autophagy is further supported by the increased cytotoxicity and the enhanced cleaved caspase-3 after co-treatment of cells with an autophagy inhibitor, also by increased LC3-II and decreased p62 after co-treatment with a caspase inhibitor. Taken together, Astin B, most likely together with other members of astins, is the substance that is primarily responsible for the hepatotoxicity of A.tataricus.
A new chlorinated cyclic pentapeptide, hydroxycyclochlorotine (1), has been isolated from Penicillium islandicum, and the structure including absolute stereochemistry of 1 and conformational properties of 1 and cyclochlorotine (2) in DMSO-d6 were elucidated by using extensive 2D NMR and chemical means. Hydroxycyclochlorotine (1) and Astin B (3) from Aster tataricus, each containing an allo threonine at residue 2, have a cis proline configuration, whereas cyclochlorotine (2) has two conformational states in solution, which may be produced from cis-trans isomerization of the proline amide bond. The presence of an intramolecular hydrogen bond between Ser (3)-NH and a hydroxyl oxygen atom of alloThr (2) may serve to maintain the backbone conformation with a cis proline amide bond.
Conformational analysis of antitumor cyclic pentapeptides, astins A (1) and C (3), was made by a combination of NMR and computational techniques. These results indicated that the backbone conformations of 1 and 3, with lower activity than Astin B (2), were different from that of 2. The backbone conformation together with a cis 3,4-dichlorinated proline residue was considered to play an important role in the antitumor activities of astins.
Result:
BioCrick is one of the biggest natural products manufacturers in Asia
Our products can be used as reference standards,inhibitors in pharmacological research
Our MISSION is to provide Best-in-class High-purity natural compounds to researchers all around the world
114420-67-6 © 2007-2024 BioCrick BioTech. All rights reserved. sitemap