Trilobolide-6-O-isobutyrate suppresses hepatocellular carcinoma tumorigenesis through inhibition of IL-6/STAT3 signaling pathway.

Currently available therapies for hepatocellular carcinoma (HCC), with a high morbidity and high mortality, are only marginally effective and with sharp adverse side effects, which makes it compulsory to explore novel and more effective anticancer molecules. Chinese medicinal herbs exhibited prominent anticancer effects and were applied to supplement clinical cancer treatment. Here, we reported a compound, trilobolide-6-O-isobutyrate (TBB), isolated from the flowers of Wedelia trilobata with a markedly cytotoxic effect on HCC cells. We found that TBB time- and dose-dependently inhibited HCC cells' growth and colony formation in vitro. Moreover, TBB induced cell cycle arrest at the G2/M phase, mitochondrial caspase-dependent apoptosis, and suppressed migration and invasion, as well as the glycolysis of HCC cells. Mechanistically, our data indicated that TBB inhibited the STAT3 pathway activation by directly interacting with the TYR 640/657 sites of the STAT3 protein and decreasing the level of p-STAT3. TBB also regulated the expression of PCNA, Ki67, Cyclin B1, Cyclin E, Bax, Bcl2, MMP2/9, and PGK1 through the inhibition of the IL-6/STAT3 signaling pathway. Lastly, we confirmed that TBB effectively eliminated tumor growth without causing overt toxicity to healthy tissues in the xenograft tumor model. The exploration of anticancer activity and the underlying mechanism of TBB suggested its usage as a promising chemotherapeutic agent for HCC.

Two new lactam derivatives from a Sphagneticola trilobata derived fungus Penicillium rubens PQJ-2.

A new bicyclic lactam derivatives penicilactam B (1) and a new monocyclic amide penicillamide D (2), along with four known compounds (3-6), were isolated from the fermentation broth of the derived fungus Penicillium rubens PQJ-2. Their structures and stereochemistry were elucidated by comprehensive spectroscopic analyses and quantum ECD calculations. All the compounds were evaluated for their antibacterial activities against Staphylococcus aureus subsp, Candida albicans, Escherichia coli and insecticidal activity against Helicoverpa armigera Hubner. Compounds 1-3 exhibited modest insecticidal activity against H. armigera Hubner.

Phytochemical investigation of the flowers of Praxelis clematidea (Griseb.) R.M. King & H. Rob.

Chemical investigations of the flowers of Praxelis clematidea resulted in the isolation of 12 known compounds (1-12). Their structures were elucidated by extensive spectroscopic studies and chemical evidence. The structure and absolute configuration of 1 was precisely determined by a combination of 2 D NMR and quantum chemical calculations of ECD spectra analysis. Compounds 1, 4, 11 were isolated from the genus Praxelis for the first time, while 1-6, 8-12 were isolated from P. clematidea for the first time. The antibacterial activity of compounds 1, 2, 7, 9 were evaluated.