Daphnane-type diterpenoids from Stellera chamaejasme L. and their inhibitory activity against hepatocellular carcinoma cells.

Daphnane-type diterpenoids, which are scarce in nature, exhibit potent growth-inhibitory activities against various cancer cells. To identify more daphnane-type diterpenoids, the phytochemical components in the root extracts of Stellera chamaejasme L. were analysed in this study using the Global Natural Products Social platform and the MolNetEnhancer tool. Three undescribed 1α-alkyldaphnane-type diterpenoids (1-3; named stelleradaphnanes A-C) and 15 known analogues were isolated and characterised. The structures of these compounds were determined using ultraviolet and nuclear magnetic resonance spectroscopy. The stereo configurations of the compounds were determined using electronic circular dichroism. Next, the growth-inhibitory activities of isolated compounds against HepG2 and Hep3B cells were examined. Compound 3 exhibited potent growth-inhibitory activities against HepG2 and Hep3B cells with half-maximal inhibitory concentration values of 9.73 and 15.97 µM, respectively. Morphological and staining analyses suggested that compound 3 induced apoptosis in HepG2 and Hep3B cells.

Stellerasespenes A‒E: Sesquiterpenoids from Stellera chamaejasme and their anti-neuroinflammatory effects.

Five undescribed sesquiterpenoids stellerasespenes A‒E and four reported congeners were isolated from the roots of Stellera chamaejasme. The structures were elucidated by comprehensive spectroscopic analyses together with X-ray single crystal diffraction and theoretical calculations. The structure of holosericin B was revised. All the isolated compounds were evaluated for NO production in murine microglial BV2 cells induced by LPS. Stellerasespene A showed better inhibitory activity than the positive control minocycline, inhibiting NO production and overexpression of pro-inflammatory cytokine IL-1ß in LPS-activated BV2 cells.

Chamaejasmenin E from Stellera chamaejasme induces apoptosis of hepatocellular carcinoma cells by targeting c-Met in vitro and in vivo.

Hepatocellular carcinoma (HCC), the most prevalent liver cancer, is considered one of the most lethal malignancies with a dismal outcome. There is an urgent need to find novel therapeutic approaches to treat HCC. At present, natural products have served as a valuable source for drug discovery. Here, we obtained five known biflavones from the root of Stellera chamaejasme and evaluated their activities against HCC Hep3B cells in vitro. Chamaejasmenin E (CE) exhibited the strongest inhibitory effect among these biflavones. Furthermore, we found that CE could suppress the cell proliferation and colony formation, as well as the migration ability of HCC cells, but there was no significant toxicity on normal liver cells. Additionally, CE induced mitochondrial dysfunction and oxidative stress, eventually leading to cellular apoptosis. Mechanistically, the potential target of CE was predicted by database screening, showing that the compound might exert an inhibitory effect by targeting at c-Met. Next, this result was confirmed by molecular docking, cellular thermal shift assay (CETSA), as well as RT-PCR and Western blot analysis. Meanwhile, CE also reduced the downstream proteins of c-Met in HCC cells. In concordance with above results, CE is efficacious and non-toxic in tumor xenograft model. Taken together, our findings revealed an underlying tumor-suppressive mechanism of CE, which provided a foundation for identifying the target of biflavones.

Guaiane-type sesquiterpenoids from the roots of Stellera chamaejasme L. and their neuroprotective activities.

Nine undescribed guaiane-type sesquiterpenoids stelleraterpenoids A‒I, along with seven reported congeners, were isolated and identified from the 70% EtOH extract of the roots of Stellera chamaejasme L. Their chemical structures were elucidated on the basis of various spectral data. The relative configurations were determined by their NOESY spectra and comparison between their experimental and calculated NMR data. The absolute configurations were established by the comparison between the experimental and calculated ECD spectra and further by X-ray single-crystal diffraction analysis. The neuroprotective effects of these compounds on the H2O2-induced damage in human neuroblastoma SH-SY5Y cells were evaluated. Stelleraguaianone B exhibited the better activity with 71.62% cell viability compared to the positive control Trolox (65.05%) at 12.5 µM, which might be achieved by inhibiting the apoptosis of SH-SY5Y cells based on an annexin V-FITC/PI staining experiment.

Isolation and structure elucidation of anti-tyrosinase compounds from the seeds of Crotalaria pallida.

Three new compounds, crotalariapallins A-C (1-3), were isolated from the 95% EtOH extract of the seeds of Crotalaria pallida. Their structures were established based on extensive spectroscopic methods, including HRESIMS, UV, 1D and 2D NMR. All compounds were evaluated for their inhibitory activities to tyrosinase. These compounds showed different degrees of inhibitory activities, among them, compound 3 exhibited the strongest inhibition activity (IC50 = 0.42 mM).

Sesquiterpenes from Echinacea purpurea and their anti-inflammatory activities.

Six unreported sesquiterpenes, purpureaterpenes A‒F, together with six known sesquiterpenes, were isolated and identified from the aerial part of Echinacea purpurea. Their chemical structures were established by detailed analyses of 1D and 2D NMR data. The relative configurations were assigned on the basis of their NOESY spectra and the calculated 13C NMR spectra. Their absolute configurations were determined by X-ray crystallographic analyses and optical rotation calculations. All the isolated compounds were tested for their anti-inflammatory effects against NO production in LPS-induced RAW246.7 macrophages. Among these compounds, purpureaterpene E was the most active (IC50 value 13.27 µM), even better than the positive control, minocycline (IC50 value 34.81 µM). Further investigation found that purpureaterpene E might exert anti-inflammatory property via the NF-κB signaling pathway.

Chiral resolution and bioactivity of enantiomeric furofuran lignans from Juglans mandshurica Maxim.

Enantiomers have generally been reported mostly for racemic mixtures with a 1:1 ratio, as in that case there were weak Cotton effects in the ECD spectrum and negligible optical rotations. A furofuran lignan (sesamin), with a remarkable rotation and significant Cotton effects, was isolated from Juglans mandshurica Maxim. Subsequently, sesamin was resolved by chiral HPLC to afford a pair of enantiomers, (+)-sesamin (a) and (-)-sesamin (b), in a ratio of approximately 1:3. Their absolute configurations were determined by computational analysis of their electronic circular dichroism (ECD) spectrum. In addition, the pair of enantiomers were evaluated for the inhibition of self-induced Aß aggregation. Interestingly, (+)-sesamin (a) (67.7%) and (-)-sesamin (b) (80.6%) exhibited different degrees of anti-Aß aggregation activity. The different inhibition profiles were further explained by molecular dynamics and docking simulation study.

Sesquiterpenoids from the herbs of Solanum lyratum and their cytotoxicity on human hepatoma cells.

Eleven sesquiterpenoids including four new eudesmane sesquiterpenoids, solanoids A-D (1-4), and seven known compounds (5-11) were isolated from the herbs of Solanum lyratum. By analyzing the UV, MS and NMR data, the gross structures of all isolates were established. The absolute configurations of these new compounds were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity of all isolates against the hepatocellular carcinoma Hep3B and HepG2 cell lines was evaluated. Among them, compounds 7 and 11 exhibited moderate cytotoxicity against two cell lines.

Seven new neuroprotective sesquineolignans isolated from the seeds of Crataegus pinnatifida.

The investigation of the ethanol extract of the seeds of Crataegus pinnatifida led to the isolation of seven new 8-O-4' type sesquineolignans crasesquineolignan A-G (1-7), along with a reported analogue, leptolepisol B (8). The chemical structures of these compounds were elucidated based on complex analysis of their MS, 1D and 2D NMR data. All the isolated compounds were tested for their neuroprotective effects against the damage of human neuroblastoma SH-SY5Y cells induced by H2O2, and most of them showed significant neuroprotective activity. Among them, compound 4 (77.58%) showed the best protective effect, even better than the positive control (69.26%) at 25 µM.

Alkaloids from Juglans Mandshurica maxim induce distinctive cell death in hepatocellular carcinoma cells.

The aim of this work was to further investigate the anticancer potential of Juglans mandshurica Maxim, including the separation of active constituents and their anti-proliferative effects with underlying mechanism of action. Five alkaloids (1-5) were isolated from the bark of J. mandshurica. Among them, 1 showed the highest cytotoxic activities against Hep3B and HepG2 cells with an IC50 values of 61.80 and 56.24 µM, respectively. Therefore, the cellular mechanism involved 1 was subsequently studied. Our results showed that 1 markedly caused apoptosis and autophagy, but without cell cycle arrest in HepG2 cells. Interestingly, only autophagic cell death was induced in 1-treated Hep3B cells. It is concluded that the isolated alkaloids exerted a certain anti-hepatoma potential, and our results may provide a basis for the further investigation of the alkaloids extracted from J. mandshurica.

A new coumarin from Juglans mandshurica Maxim induce apoptosis in hepatocarcinoma cells.

In this study, a new coumarin, juglansoside C (1) was isolated from the bark of Juglans mandshurica. Its chemical structure was identified by comprehensive spectroscopic analyses. The in vitro cytotoxicity assay showed that 1 exhibited moderate cytotoxicity against human hepatocellular carcinoma Hep3B cells with an IC50 value of 70.9 µM. Furthermore, Annexin V-FITC/PI staining assay indicated that 1 markedly induced apoptosis in Hep3B cells.

Phenylpropanoids and lignans from Prunus tomentosa seeds as efficient ß-amyloid (Aß) aggregation inhibitors.

Alzheimer's disease (AD) is characterized by the progressive accumulation of extracellular ß-amyloid (Aß) aggregates. Recently, lignans and phenylpropanoids are attracting increasing attention to discovery useful agents of inhibition on Aß aggregation. In the present study, to develop potential agents for slowing the progression of AD, Prunus tomentosa seeds were selected as a raw material for bioactive compounds, which led to the separation of two pairs of new enantiomeric lignans and phenylpropanoids using chiral HPLC. The planar structures of these compounds were elucidated by spectroscopic data analyses. And their absolute configurations were determined by comparing of experimental and calculated electronic circular dichroism (ECD). The biosynthesis pathway was also discussed. Additionally, the inhibitory activity on Aß aggregation of all optical pure compounds was tested by thioflavin T (ThT) assay. The isolates (1a, 1b, 2a and 2b) showed more potent inhibitory activity than positive control curcumin with inhibitory rate of 73.89 ±â€¯3.41% 78.69 ±â€¯1.50%, 63.25 ±â€¯2.68%, and 67.13 ±â€¯0.90% at 20 µM, respectively. More importantly, the inhibition profiles were explained by molecular dynamics and docking simulation studies.

Cytotoxic lignans from the barks of Juglans mandshurica.

Phytochemical investigation of the barks of Juglans mandshurica Maxim led to the isolation, purification, and identification of one new lignan named Juglansol A (1), along with nine known compounds (2-10). Their structures were determined by the results of UV, IR, CD, HRESIMS, 1D, and 2D NMR spectroscopic analysis. Compounds 1-10 were evaluated for their cytotoxicities against A549, HepG2, Hep3B, Bcap-37, and MCF-7 cell lines. The results showed that compound 2 possessed stronger cytotoxicities against the tested tumor cell lines compared with positive control 5-fluorouracil.

Coumarins from the bark of Juglans mandshurica exhibited anti-hepatoma activities via inducing apoptosis.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer from Juglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract. The structures of these compounds were determined by 1D and 2D NMR experiments. The absolute configuration of 1 was established by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity experiments on two liver cancer cell lines (HepG2 and Hep3B) showed that compounds 2 and 5 had moderate antitumor activities on both cell lines. And further studies of antitumor mechanisms by the observation of morphological changes and Western blot analyses exhibited that induction of apoptosis might be a possible way that inhibited cell growth.

Phenylpropanoids from Juglans mandshurica exhibit cytotoxicities on liver cancer cell lines through apoptosis induction.

Three new phenylpropanoids (1-3) together with six known congeners (4-9) were isolated from the bark of Juglans mandshurica Maxim using anti-hepatoma activity as a guide. Their structures were determined by comprehensive NMR and HRESIMS spectroscopic data analyses. All the isolated compounds were evaluated for their growth inhibitory activities against two kinds of liver cancer cell lines (HepG2 and Hep3B). Among them, compound 4 showed moderate cytotoxic activities against HepG2 and Hep3B cell lines with IC50 values of 58.58 and 69.87µM. Compound 5 exhibited 50% cell death rate in HepG2 and Hep3B cell lines at 63.70 and 46.45µM, respectively. Further observation of morphological changes and Western blot demonstrated that compounds 4 and 5 exhibited their cytotoxic activities through the induction of apoptosis. A structure-activity relationship study suggested that an α, ß-unsaturated aldehyde might be the most important functional group.