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.

Discovery of alkaloids from the leaves of Isatis indigotica Fortune with neuroprotective activity.

Seven alkaloids including five undescribed ones (1a/1b, 2, 3 and 5) were obtained from the leaves of Isatis indigotica Fortune. Their structures were established by extensive spectroscopic analyses. The absolute configurations of compounds 1a, 1b, 3 and 5 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Subsequently, the neuroprotective effects of all the isolates against H2O2-induced injury in SH-SY5Y cells were evaluated in vitro by MTT assay. Moreover, Annexin V-FITC/PI double staining was performed, while the activities of antioxidant enzymes (SOD, CAT and GSH-Px) for compounds 1a and 1b were measured.

The first record of the genus Belenois (Lepidoptera: Pieridae) from China.

BACKGROUND: The family Pieridae is a large group of butterflies which plays an important role in evolutionary biology and contains many potential pests (Courtney 1986). Pieridae is a cosmopolitan family while the tropics harbour higher species richness. In a very recent expedition to the Chinese-Indian border area in Tibet Autonomous Region, a migratory species, Belenois aurota (Fabricius, 1793), was discovered for the first time, which comprises the first record of the genus Belenois in China and the highest altitude record of this species. NEW INFORMATION: The species B. aurota (Fabricius, 1793) is the first record of the genus Belenois from China. The specimen was collected at an altitude of about 3,000 m in Tibet Autonomous Region. Relevant details are presented for the species.

Network pharmacology predicted HDAC6 as a potential target of flavones from Daphne giraldii on hepatocellular carcinoma.

Daphne giraldii Nitsche, belongs to Daphne genus, has been reported to exert anti-tumor activities. Our previous study suggested that flavones from Daphne giraldii have significant inhibitory effects on hepatocellular carcinoma (HCC) cells. However, the potential target of this type flavone was still unknown. In this study, 74 flavonoids compounds of Daphne giraldii and 41 potential targets of HCC were analyzed by the network, the most potential target was histone deacetylase 6 (HDAC6). Considering the cytotoxicity, compound 70 (Daphnegiravone D, DGD) was chosen for further confirmation. Molecular docking study revealed that DGD formed high binding affinity with HDAC6. Concomitantly, pharmacological studies indicated that DGD could inhibit the expression of HDAC6 in vitro and in vivo. In this study, network pharmacology along with experimental validation predicted and verified HDAC6 as one of potential targets of flavones, these investigations provide a new insight for further study of Daphne giraldii on HCC treatment.

Terpenoids from stigma maydis (Zea mays L.) alleviate hydrogen peroxide-induced SH-SY5Y cell injury by activating Nrf2.

Five terpenoids (1-5), including three new ent-kaurane diterpenoids (1-3), one new ent-rosane type diterpenoid (4) and one known triterpenoid (5), were isolated from stigma maydis (Zea mays L.). The structures of the compounds were elucidated by comprehensive spectroscopic analyses. The relative configurations of stigmanes A-D (1-4) were determined by NOESY experiments. In addition, the relative configuration of stigmane D (4) was further established by NMR calculations. The absolute configurations of these compounds were identified by a comparison of experimental and calculated specific rotations. The neuroprotective effects of these compounds against H2O2-induced injury in human neuroblastoma SH-SY5Y cells were evaluated, and the results showed that among the compounds, 2 exhibited the most significant neuroprotection. Further study demonstrated that 2 could activate nuclear factor E2-related factor (Nrf2), downregulate apoptosis and reactive oxygen species (ROS) generation, and increase antioxidant enzyme activities in SH-SY5Y cells. However, the neuroprotective effect was reversed when Nrf2 was silenced. In conclusion, this study suggested that terpenoids from stigma maydis exerted neuroprotective effects through Nrf2 activation.

Phenolics from Archidendron clypearia (Jack) I.C.Nielsen protect SH-SY5Y cells against H2O2-induced oxidative stress.

Five undescribed phenolics named pithecellobiumin C-G, along with thirteen known ones were isolated from the twigs and leaves of Archidendron clypearia (Jack) I.C.Nielsen. Their structures were elucidated based on comprehensive spectroscopic analyses, combined with computer-assisted structure elucidation software (ACD/Structure Elucidator) and gauge-independent atomic orbitals (GIAO) NMR chemical shift calculations. The absolute configurations were determined by comparison of experimental and calculated specific rotation and ECD curves. These compounds were tested for their neuroprotective activities against H2O2-induced injury in human neuroblastoma SH-SY5Y cells by MTT assay. Pithecellobiumin C-E exhibited noticeable neuroprotective effect. Further pharmacological study demonstrated that they could prevent cell death through inhibiting the apoptosis induction. Flow cytometry assays also proved that these compounds could attenuate reactive oxygen species (ROS) level and mitochondrial dysfunction in SH-SY5Y cells.

Four pairs of alkaloid enantiomers from Isatis indigotica Fortune Ex Land with neuroprotective effects against H2O2-induced SH-SY5Y cell injury.

In the current study, four pairs of new enantiomeric alkaloids (1a/1b-4a/4b) were obtained from the leaves of Isatis indigotica Fortune Ex Land. Their structures were elucidated through spectroscopic methods and quantum mechanical calculations. Biologically, all isolates were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury. As a result, 1a and 1b exhibited enantioselective neuroprotective effects, further Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 20.93% and 17.87%, respectively.

Guaiane-Type Sesquiterpenoids from the Roots of Daphne genkwa and Evaluation of Their Neuroprotective Effects.

Chromatographic purification of the roots of Daphne genkwa led to 11 new guaiane-type sesquiterpenoids (1-11), named genkwanoids A-K, and six known analogues (12-17). A comprehensive set of spectroscopic methods including IR, UV, HRESIMS, and 1D/2D NMR were used to elucidate the structures and relative configurations of 1-11. The absolute configurations were determined by the optical rotation calculations and the modified Mosher's method. The possible biosynthetic pathways for 1-11 are proposed. Furthermore, the neuroprotective effects of 1-17 on H2O2-induced damage in human neuroblastoma SH-SY5Y cells were screened using an MTT assay. Compounds 9, 10, and 16 exhibited moderate neuroprotective effects, with survival rates of 79.34%, 79.94%, and 75.64% after treatment with 12.5 µM, values that were comparable to the positive control, Trolox (78.65%). Furthermore, annexin V-FITC/PI staining of cells treated with 9, 10, and 16 showed that the neuroprotective effects of these compounds may arise from inhibiting cell apoptosis.

Isolation of enantiomeric furolactones and furofurans from Rubus idaeus L. with neuroprotective activities.

A phytochemical study on the fruits of Rubus idaeus L. (Rosaceae) yielded eight pairs of enantiomeric lignans, including one undescribed furolactone named (-)-idaeusinol A and six undescribed furofuran derivatives named (+/-)-idaeusinol B-D. The structures of these isolated compounds were elucidated by spectroscopic analyses and a combination of computational techniques including gauge-independent atomic orbital (GIAO) calculation of 1D NMR data and TD-DFT calculation of electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that (+)-idaeusinol D exhibited the most significant protective effect against H2O2-induced neurotoxicity at the concentration of 25 µM. In contrast, (-)-idaeusinol D, as the enantiomer of (+)-idaeusinol D, showed no effect against H2O2-induced neurotoxicity at both 25 and 50 µM concentration.

Chiral resolution and neuroprotective activities of enantiomeric 8-O-4' neolignans from the fruits of Crataegus pinnatifida Bge.

Five pairs of enantiomeric 8-O-4' neolignans (1a/1b-5a/5b), including seven new compounds (1a/1b, 2a, 3a, 4a/4b and 5b), were obtained from the fruits of Crataegus pinnatifida Bge. Their structures were determined by comprehensive spectroscopic analyses. The absolute configurations of the enantiomers were determined by comparison of the experimental ECD with the calculated data. Additionally, all the enantiomeric neolignans were evaluated for their neuroprotective activity against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells, and most of them showed potent selective neuroprotective activity. Especially, 3b (72.98%) showed the best protective effect, better than 3a (63.49%) and trolox (62.86%) at 25 µM.

Timosaponin AIII, a steroidal saponin, exhibits anti-tumor effect on taxol-resistant cells in vitro and in vivo.

Timosaponin AIII (TAIII), a steroidal saponin isolated from the rhizome of Anemarrhena asphodeloides, exerted cytotoxic effect in many cancer cell lines. However, the effect of TAIII on resistant tumor cancer cells was unclear. In this study, MTT assay showed that TAIII exhibited significant cytotoxicity against A549/Taxol and A2780/Taxol cells in vitro. Annexin V-FITC/PI staining revealed that TAIII induced apoptosis in A549/T and A2780/T cells. Furthermore, Western blot analysis demonstrated that TAIII inhibited the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) as well as Ras, Raf, mitogen-activated protein kinase (MEPK), extracellular regulated protein kinases (ERK) in two taxol-resistant cancer cell lines. Besides, in vivo studies demonstrated that TAIII inhibited tumor growth in a nude mouse xenograft model. Additionally, TAIII (2.5 and 5 mg/kg) also down-regulated the protein expressions of PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways in vivo. Taken together, these findings demonstrated that TAIII exhibited significant anti-tumor effect on taxol-resistant cells.

Chiral resolution and neuroprotective activities of enantiomeric dihydrobenzofuran neolignans from the fruit of Crataegus pinnatifida.

Three pairs of enantiomeric dihydrobenzofuran neolignans (1a/1b-3a/3b) including four new compounds (1a/1b and 2a/2b) were isolated from the fruit of Crataegus pinnatifida. Their structures including the absolute configurations were elucidated by extensive spectroscopic analyses and comparison between the experimental measurements of electronic circular dichroism (ECD) and the calculated ECD spectra. Additionally, all the enantiomeric neolignans were investigated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. It was found that enantiomers 1a and 1b displayed different degrees of neuroprotective activities, and the results showed enantioselectivity, in which that 1b exhibited noticeable neuroprotective activity, while its enantiomer 1a only exhibited obvious protective effect at lower concentration. Further study demonstrated that the potential protective activities of compounds appeared to be mediated via suppressing cell apoptosis.

Timosaponin AIII: A novel potential anti-tumor compound from Anemarrhena asphodeloides.

Timosaponin AIII, a major steroidal saponin found in Anemarrhena asphodeloides Bge., which has been widely used as anti-pyretic, anti-diabetic, anti-inflammatory, anti-platelet aggregator and anti-depressant agents in traditional Chinese medicine. Recent pharmacological study showed that timosaponin AIII had potent cytotoxicity, which was potential to be developed as an anticancer agent, however the molecular mechanism underlying the anticancer activity has not been fully elucidated. This review aims to give a systematic summary of the study of timosaponin AIII to reveal its anti-tumor activities by investigating invasion and migration, apoptosis, autophagy and reversing multi-drug resistance. Furthermore, we also make an overview of the mechanisms identified till now. These meaningful findings may provide novel insights on exploiting timosaponin AIII as a new anti-tumor agent.