Chemical constituents from the seeds of Cullen corylifolium and their inhibitory activity on diacylglycerol acyltransferase.

A large number of extracts of medicinal plants or natural products shows beneficial to combat obesity. In the present work, a new flavonoid named (2S,1″R,2″R)-4'-hydroxy-7-methoxy-6-(1,2,3-trihydroxy-3-methyl-butyl)-flavanone (1), along with seven known compounds (2-8) were isolated from the seeds of Cullen corylifolium. Their structures, including the absolute configurations, were determined by the analysis of comprehensive spectroscopic data and computational calculation methods. All isolates were evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity. Compounds 1-4 exhibited different level of DGAT1 inhibitory activity with IC50 values ranging from 28.2 ± 1.1 to 127.3 ± 1.9 µM. In addition, 45 flavonoids which be evaluated for DGAT inhibitory activity were summarised and potential structure-activity relationships were discussed.

Scutellariabarbata D. Don extraction selectively targets stemness-prone NSCLC cells by attenuating SOX2/SMO/GLI1 network loop.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellariabarbata D. Don extraction (SBE), a traditional Chinese medicine, has been proved effective against various malignant disorders in clinics with tolerable side-effects when administered alone or in combination with conventional chemotherapeutic regimens. AIM OF THIS STUDY: Multi-drug resistance of cancer is attributed to existence of cancer stemness-prone cells that harbor aberrantly high activation of Sonic Hedgehog (SHH) cascade. Our previous study has demonstrated that SBE sensitized non-small cell lung cancer (NSCLC) cells to Cisplatin (DDP) treatment by downregulating SHH pathway. Yet, whether SBE could prohibit proliferation of cancer stemness-prone cells and its underlying molecular mechanisms remain to be investigated. In this article, we further investigated intervention of SBE on NSCLC cell stemness-associated phenotypes and its potential mode of action. MATERIALS AND METHODS: CCK-8 and clonal formation detection were used to measure the anti-proliferative potency of SBE against NSCLC and normal epithelial cells. Sphere formation assay and RQ-PCR were used to detect proliferation of cancer stemness cells and associated marker expression upon SBE incubation. Mechanistically, DARTS-WB and SPR were used to unveil binding target of SBE. Immunodeficient mice were implanted with patient derived tumor bulk for in vivo validation of anti-cancer effect of SBE. RESULTS: SBE selectively attenuated proliferation and stemness-like phenotypes of NSCLC cells rather than bronchial normal epithelial cells. Drug-protein interaction analysis revealed that SBE could directly bind with stem cell-specific transcription factor sex determining region Y-box 2 (SOX2) and interfere with the SOX2/SMO/GLI1 positive loop. In vivo assay using patient-derived xenografts (PDXs) model further proved that SBE diminished tumor growth and SOX2 expression in vivo. CONCLUSION: Our data indicate that SBE represses stemness-related features of NSCLC cells via targeting SOX2 and may serve as an alternative therapeutic option for clinic treatment.

Cytotoxic and Antiviral Triterpenoids from the Mangrove Plant Sonneratia paracaseolaris.

A chemical investigation was conducted on the aerial parts of the mangrove plant Sonneratia paracaseolaris, yielding five new triterpenoid paracaseolins A-E (1-4, and 11) together with twelve known analogues (5-10, 12-17). Their structures were established by extensive spectroscopic methods and comparisons their spectroscopic data with those of the known related compounds. The cytotoxicities against P388, HeLa, A549, and K562 tumor cell lines and anti-H1N1 (Influenza A virus) activities for the isolates were evaluated. Compound 4 showed potent cytotoxicity against the A549 cell line with an IC50 value of 1.89 µM, and compound 1 exhibited significant anti-H1N1 virus activity with an IC50 value of 28.4 µg/mL. A preliminary structure activity relationship was discussed.