Dajian Yang

Cantharimide and Its Derivatives from the Blister Beetle Mylabris phalerata Palla.

Eleven new monoterpenoids including three 1-methyl cantharimide-type derivatives (1-3), five 1,2-dimethyl cantharimide-type derivatives (4, 5, 7-9), and three 1-hydroxymethyl-2-methyl cantharimide-type derivatives (10-12), together with seven known cantharimides (6, 13-18), were isolated from Mylabis phalerata Palla. The planar structures and absolute configurations of compounds 1-14 were fully elucidated on the basis of spectroscopic analysis, ECD spectra, single-crystal X-ray diffraction analysis, and chemical methods. Compounds 6, 15, 16, and 18 were found to be potent inhibitors of HBV virus, with IC50 values of 62, 42, 58, and 19 μM.

Wilfordonols A–D: four new norsesquiterpenes from the leaves of Tripterygium wilfordii

Four new norsesquiterpenes wilfordonols A–D (1–4), along with three known compounds, sarmentol B (5), boscialin (6), and (+)-loliolide (7), were isolated from the leaves of Tripterygium wilfordii Hook.f.. The structures of the new compounds were elucidated on the basis of their spectroscopic analysis, and the absolute configuration of the compounds was confirmed by CD and modified Moshers method. At a concentration of 10 μM, compounds 4, 6, and 7 inhibited signal transducer and activator of transcription 1 translocation by 34.27 ± 1.02%, 48.93 ± 1.76%, and 70.31 ± 2.20%, respectively.

Ginsenoside 20(S)-Rh2 Induces Apoptosis and Differentiation of Acute Myeloid Leukemia Cells: Role of Orphan Nuclear Receptor Nur77

Ginsenoside 20(S)-Rh2 has been shown to induce apoptosis and differentiation of acute myeloid leukemia (AML) cells. However, the underlying molecular mechanisms are not fully understood. In our study, 20(S)-Rh2 induced the expression of orphan nuclear receptor Nur77 and death receptor proteins Fas, FasL, DR5, and TRAIL, as well as the cleavage of caspase 8 and caspase 3 in HL-60 cells. Importantly, shNur77 attenuated 20(S)-Rh2-induced apoptosis and Fas and DR5 expression. Meanwhile, 20(S)-Rh2 promoted Nur77 translocation from the nucleus to mitochondria and enhanced the interaction between Nur77 and Bcl-2, resulting in the exposure of the BH3 domain of Bcl-2 and activation of Bax. Furthermore, 20(S)-Rh2 promoted the differentiation of HL-60 cells as evidenced by Wright-Giemsa staining, NBT reduction assay, and detection of the myeloid differentiation marker CD11b by flow cytometry. Notably, shNur77 reversed 20(S)-Rh2-mediated HL-60 differentiation. Additionally, 20(S)-Rh2 also exhibited an antileukemic effect and induced Nur77 expression in NOD/SCID mice with the injection of HL-60 cells into the tail vein. Together, our studies suggest that the Nur77-mediated signaling pathway is highly involved in 20(S)-Rh2-induced apoptosis and differentiation of AML cells.

A metabolomics study on the immunosuppressive effect of Tripterygium hypoglaucum (Levl.) Hutch in mice: The discovery of pathway differences in serum metabolites

Tripterygium hypoglaucum (Levl.) Hutch (THH), a typical traditional Chinese medicine, is widely used in clinical practice for the treatment of rheumatoid arthritis, systemic lupus erythematous, and other connective tissue and autoimmune diseases. However, most related researches focused on the pharmacological effects of THH, while less attention has been paid to the immunosuppressive mechanism. The present study aims to determine the metabolic profiles, based on UPLC-Q-TOF-MS, identify differential metabolites, and find related metabolic pathways among the sensitization red blood cell (SRBC) model mice, THH treated mice, and cyclophosphamide treated group. Totally, 24 and 19 changed metabolites were found in the THH and cyclophosphamide treated groups respectively. Among them, we found that urocanate metabolic pathway change could be considered as the most relevant pathway associated with immunosuppression. This is the first study that comprehensively assessed the differences in metabolome between the model and THH treated groups. The results provide insights into the difference between the immunosuppressive mechanisms of THH and cyclophosphamide and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of drugs in the treatment of diseases and the associated mechanism involved.