The nature compound dehydrocrenatidine exerts potent antihepatocellular carcinoma by destroying mitochondrial complexes in vitro and in vivo.

Cumulative evidence indicates that mitochondria dysfunction plays an important role in tumour treatment. Given the limited efficacy and toxicity of current mitochondria-targeted drugs, research into effective mitochondria-targeted anticancer agents remains an irresistible general trend. In this study, it was found that dehydrocrenatidine (DEC), a ß-carbolin alkaloid isolated from Picrasma quassiodes, displays a promising growth inhibitory effect in vitro and in vivo by inducing apoptosis of hepatocellular carcinoma (HCC) cells. Mechanistically, we provided that the possible target of DEC against HCC cells was determined by isobaric labels for relative and absolute quantification assay and validated them using further experiments. The results suggested that DEC can target and regulate the function of mitochondrial complexes I, III and IV, affecting oxidative phosphorylation and ultimately leading to mitochondrial dysfunction to exert its anti-HCC effects. In addition, the combination of DEC and sorafenib showed a synergistic effect and was also associated with mitochondrial dysfunction. Importantly, DEC did not show significant toxicity in mice. This study provided a new insight into underlying mechanisms in DEC-treated HCC cells, suggesting that DEC might be a mitochondrial targeting lead compound.

Benzoic acid derivatives from the root barks of Ailanthus altissima.

Two new benzoic acid derivatives (1-2), together with four known compounds (3-6) have been isolated from the n-BuOH soluble fraction of ethanolic extract from Ailanthus altissima. The gross structures of the new compounds were deduced by detailed spectroscopic analysis including HRESIMS and 1D/2D NMR spectroscopy. The stereochemistry of 1 was determined by modified Mosher's method. All compounds were evaluated for their neuroprotective effects against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells and none of them displayed obvious neuroprotective activities. [Formula: see text].

Modified lanostane-type triterpenoids with neuroprotective effects from the fungus Inonotus obliquus.

Six undescribed lanostane triterpenoids (1-6), together with three known compounds (7-9) were isolated from Inonotus obliquus. Compounds 3-5 are the rare natural compounds featuring a 4,5-seco-lanostane core with a 5,7,9-trien-21,24-cyclopentane moiety. The structure elucidation of the compounds was conducted by spectroscopic techniques and the ECD method. The absolute configuration of compound 1 was confirmed by single-crystal X-ray diffraction analysis. All isolated compounds were assayed for their neuroprotective activity against H2O2-induced cell injury using human neuroblastoma SH-SY5Y cells. Compound 9 exhibited the most potent neuroprotective activity and the flow cytometry analysis indicated that 9 could protect SH-SY5Y cells from oxidative damage by inhibiting cell apoptosis.

Lignans and neolignans with isovaleroyloxy moiety from Solanum lyratum Thunb.: Chiral resolution, configurational assignment and neuroprotective effects.

Eight pairs of enantiomeric lignans and neolignans including thirteen undescribed compounds, along with an undescribed meso compound, were isolated from the herbs of Solanum lyratum Thunb.(Solanaceae). Their structures and relative configurations were determined by extensive spectroscopic analyses of HRESIMS and nuclear magnetic resonance. The absolute configurations of the pure isomers were established based on the cooperative comparison between the experimental and calculated electronic circular dichroism (ECD) and optical rotation (OR). It is interesting that we obtained several naturally occurring stereoisomers with the identical gross structure possessing several stereogenic carbons from S. lyratum. Additionally, all isolates were assessed for neuroprotective effects toward human neuroblastoma SH-SY5Y cells injury induced by H2O2.

Chiral-phase resolution of sesquilignans from raspberries (Rubus idaeus L.) and their neuroprotective effects.

Two pairs of diastereoisomers (1/2 and 3/4) were isolated from the fruits of Rubus idaeus L. (Rosaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses. Then chiral-phase HPLC resolution gave 1a/1b-4a/4b. Their absolute configurations were determined by comparison of the experimental ECD with the calculated data. Moreover, all isolated compounds were investigated for the neuroprotective effects against H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Y cells, and 2a (66.04%) exhibited moderate neuroprotective effects, better than trolox (60.54%) at the concentration of 25 µM.

Sesquineolignans derivatives with neuroprotective activity from the fruits of Crataegus pinnatifida.

Ten undescribed sesquineolignans (1-10), including four sesqui-norlignans (1-4), were isolated from the fruits of Crataegus pinnatifida. Their structures were determined by comprehensive spectroscopic analyses. All compounds were examined for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. Among them, 6 and 8 showed comparable protective effect with 79.36% and 80.72% cell viability compared with the positive control Trolox (78.64%) at 25 µM.

Dihydro-ß-agarofuran sesquiterpenoid derivatives with neuroprotective activity from the leaves of Tripterygium wilfordii.

A phytochemical investigation on the leaves of Tripterygium wilfordii Hook. F. was conducted, leading to the isolation of five undescribed dihydro-ß-agarofuran sesquiterpenoids (1-5) and one known analogue (6). Their structures were determined by comprehensive spectroscopic analyses. The absolute configurations of the compounds were determined by comparison of the experimental ECD with the calculated data. In addition, all the compounds were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells, and 3 showed the better protective effect with 76.63% cell viability comparing with the positive control Trolox (69.84%) at 12.5 µM.

Isolation of macrocarpene-type sesquiterpenes from stigma maydis with neuroprotective activities.

Five undescribed macrocarpene-type sesquiterpenes (1-5), along with a known analogue (6) were isolated from the crude extract of stigma maydis. The structures of these compounds were elucidated based on comprehensive spectroscopic analyses together with quantum chemical calculations of 13C NMR data and electronic circular dichroism (ECD) curves. All isolated compounds were tested for their neuroprotective effects against the injury of human neuroblastoma SH-SY5Y cells induced by H2O2. Among them, compounds 3 (65.89%) and 5 (64.38%) showed moderate neuroprotective activity at 50 µM.

Alkaloid Enantiomers from Isatis tinctoria with Neuroprotective Effects against H2O2-Induced SH-SY5Y Cell Injury.

Six pairs of alkaloid enantiomers including 11 new alkaloids (1A: /1B: -5A: /5B, 6A: ) were isolated from the leaves of Isatis tinctoria. Their structures were established by extensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and the absolute configurations of all isolates were determined by comparison of experimental and calculated electronic circular dichroism spectra. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that 5A/5B: and 6A/6B: exhibited potent neuroprotective activities at 50 µM compared with the H2O2-treated group.

Enantiomeric 8,4'-type oxyneolignans from the root barks of Ailanthus altissima (Mill.) Swingle and their neuroprotective effects against H2O2-induced SH-SY5Y cells injury.

Ailanthus altissima Swingle is a deciduous tree, belonging to the Simaroubaceae family. Phytochemical investigation of the root barks of A. altissima showed the presence of eight pairs of enantiomeric 8,4'-type oxyneolignans (1a/1b-8a/8b) including nine undescribed compounds (1b, 2a, 3a/3b, 4a/4b, 5b, 7b, 8a). Their structures were elucidated by comprehensive spectroscopic analyses, and their absolute configurations were determined by comparison of the experimental and quantum chemical calculations of electronic circular dichroism (ECD) curves. In addition, their neuroprotective effects against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells were investigated. Among them, 4a, 4b, and 8b exhibited moderate neuroprotective activity.