A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high mortality and poor prognosis. WBDC-1 is a novel highly oxidized germacranolide from the Elephantopus tomentosus in our previous work, which has excellent anti-HCC activity, but the detailed mechanism is still unclear. In this study, we found that WBDC-1 was able to inhibit the proliferation and colony formation of Hep3B and HepG2 cells, as well as the cell migration ability and EMT. In addition, WBDC-1 showed no obvious toxicity to normal liver epithelial cells L-02. The potential targets of WBDC-1 were predicted by network pharmacology, and the following verified experiments showed that WBDC-1 exerted anti-HCC effect by targeting EGFR. Mechanismly, subsequent biological analysis showed that WBDC-1 can inhibit EGFR and its downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways. Overexpression of EGFR reversed the anticancer properties of WBDC-1. Consistent with in vitro experiments, WBDC-1 was able to inhibit tumor growth and was non-toxic in xenograft tumor models. In summary, this study revealed a potential tumor suppressive mechanism of WBDC-1 and provided a novel strategy for HCC treatment. It also laid a foundation for further research on the anti-tumor effect of highly oxidized germacranolides.

Four Pairs of Neuroprotective Aryldihydronaphthalene-Type Lignanamide Enantiomers from the Herbs of Solanum lyratum.

Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40 µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.

Isolation and characterization of seven neovibsane-type diterpenoids from Viburnum odoratissimum and their neuroblastoma cell protective effects.

Seven undescribed neovibsane-type diterpenoids (1-7) were isolated from the leaves of Viburnum odoratissimum. Their planar structures and relative configurations were elucidated based on a combination of 1D and 2D NMR analysis. The absolute configurations were confirmed by Rh2(OCOCF3)4-induced ECD analysis and comparison of experimental and TDDFT-calculated ECD spectrum. Based on the empirical results of the ECD of in situ formed Rh-complexes, rapid determination of the absolute configuration of C-14 within vibsane-type diterpenoids was proposed. In addition, 3 exhibited a high neuroblastoma cell protective effect of 81.8 % at 50 µM (the control group showed a neuroblastoma cell protective effect of 56.2 % at 50 µM).

Utilization of the By-Product of Corn: Guided Identification of Bioactive Terpenoids from Stigma Maydis (Corn Silk).

Stigma maydis (corn silk) (S. maydis) is a food-based by-product of maize and possesses great nutritional and pharmaceutical value. This study aimed to explore bioactive components from S. maydis. By the guidance of bioactivity-guided approach and Global Natural Products Social (GNPS) molecular networking, 12 terpenoids were discovered from S. maydis. The structures of 11 undescribed compounds (1-11) were determined by detailed spectroscopic analyses, single-crystal X-ray diffraction analysis, specific rotation calculations, electronic circular dichroism (ECD) calculations, and NMR calculations. The neuroprotective and acetylcholinesterase (AChE) inhibitory effects of 1-12 were examined, and most of them showed significant or moderate activities. The underlying neuroprotective mechanism of 4 and 5 was revealed by Hoechst 33258, AO-EB, and JC-1 staining assays. This work illustrated the potential of S. maydis as a prospective natural source of bioactive compounds in food and pharmaceutical industries.

Stereochemical insights into structurally diverse lignanamides from the herbs of Solanum lyratum Thunb.

A chemical investigation of Solanum lyratum Thunb. (Solanaceae) afforded six pairs of enantiomeric lignanamides consisting of twelve undescribed compounds, along with two undescribed racemic mixtures, and the separations of the enantiomers were accomplished by chiral-phase HPLC. The structures of these undescribed compounds were elucidated by the analysis of spectroscopic data, NMR and electronic circular dichroism calculations. All isolated compounds were assessed for neuroprotective activities in H2O2-induced human neuroblastoma SH-SY5Y cells, and acetylcholinesterase (AChE) inhibitory activities. Among tested isolates, some enantiomeric lignanamides exhibited conspicuous neuroprotective effects and AChE inhibitory effect.

Inhibition of Bruton's Tyrosine Kinase Protects Against Burn Sepsis-Induced Intestinal Injury.

This study aimed to investigate the role and molecular mechanisms of Bruton's tyrosine kinase (BTK), a member of the Tec family in burn sepsis-induced intestinal injury. Eighty C57BL/6 mice were randomly divided into four groups: the sham group, the burn group, the burn + sepsis group, and the burn + sepsis + LFM-A13 (a selective BTK inhibitor) group. The dynamic expression profiles of BTK and p-BTK in the intestine were measured by Western blot analysis. Intestinal histopathological changes and cellular apoptosis were determined. Inflammatory cytokines in serum and intestinal tissue were examined through enzyme-linked immunosorbent assay. Myeloperoxidase (MPO) activity was determined via a colorimetric assay. Intestinal p-BTK expression in the burn+sepsis group was significantly increased compared with that in the sham and burn groups. In the burn + sepsis group, the p-BTK expression level increased over time, peaked at 12, and then decreased at 24 h. LFM-A13 administration significantly inhibited p-BTK expression in the intestine. In contrast to the sham and burn groups, the burn + sepsis group exhibited obvious histopathological changes, which gradually aggravated over time. LFM-A13 also reduced the histopathological changes and cellular apoptosis in intestinal tissues, inhibited the inflammatory cytokines IL-4, IL-6, and TNF-α in serum and intestinal tissues, and significantly inhibited the increase in intestinal MPO activity induced by burn sepsis. BTK activation is one important aspect of the signaling event that may mediate the release of the anti-inflammatory cytokine IL-4 and the pro-inflammatory cytokines IL-6 and TNF-α; oxidative stress; and intestinal cell apoptosis. Thus, it contributes to burn sepsis-induced intestinal injury.