ABSTRACT
Protein tyrosine phosphatase 1B (PTP1B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii (Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1B inhibitory ursane-type triterpenes: ursolic acid (1), 2-oxopomolic acid (2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Kinetics analyses revealed that 1 was a non-competitive PTP1B inhibitor, and 2 and 3 were mixed type PTP1B inhibitors. Compounds 1-3 and structurally related triterpenes (4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases (TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxy-urs-12-ene-28-oic acid (5), and pomolic acid-3β-acetate (6) bound at the allosteric site including α3, α6, and α7 helix of PTP1B.
Subject(s)
Humans , Enzyme Inhibitors , Chemistry , Metabolism , Fruit , Chemistry , Kinetics , Methanol , Chemistry , Molecular Docking Simulation , Molecular Structure , Plant Extracts , Chemistry , Protein Binding , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Metabolism , Protein Tyrosine Phosphatases , Rubus , Chemistry , Structure-Activity Relationship , Triterpenes , Chemistry , MetabolismABSTRACT
Crude drugs that feature the name “gui” have appeared in classical medicinal textbooks with different names,and the correspondence between their names and origins remains the subject of research and discussion. In the present study, we investigated these correspondences using the descriptions in the annotations of the Bencaojingjizhu and through our previous study that revealed the standards of weights and measures in this book. Based on this investigation, we strongly speculate that “gui” in the Bencaojingjizhu was the branch skin of Cinnamomum cassia (C. cassia) (corresponding to cinnamon sticks in the market), which fits with the descriptions about the length and weight of “gui” -related crude drugs in this book. We measured the contents of cinnamic aldehyde and coumarin in the branch skin of C. cassia, and compared these to contents in other crude drugs related to “gui” that can be obtained on the market. The contents of these two compounds in the branch skin of C. cassia were similar to those in the bark of C. cassia from Vietnam that meets the standards for cinnamon bark in the Japanese Pharmacopoeia and is regarded as high-grade in the market. These results support our speculation, and it might be possible that the branch skin of C. cassia can be used as medicine instead of cinnamon bark.
ABSTRACT
High performance liquid chromatography coupled with on-line electrospray tandem mass spectrometry (HPLC/ESI-MS/MS) was used to identify C21 steroidal glycosides in the roots of Cynanchum atratum. The structures of C21 steroidal glycosides were deduced from mass fragments features in positive and negative mode. The constituents of C. atratum were separated and detected. 7 compounds were identified by comparing their ESI-MS/MS data with the reference compounds and 2 compounds were inferred solely by the ESI-MS/MS data. The method is sensitive, and provides good separation and rapid qualitative characterization of C21 steroidal glycosides in the roots of C. atratum.