Xiao-Bo Wang

Flavonoids and their derivatives with β-amyloid aggregation inhibitory activity from the leaves and twigs of Pithecellobium clypearia Benth

To explore potential compounds with marked effect on Alzheimers disease (AD) in Pithecellobium clypearia Benth., nineteen compounds (1-19) were obtained, including two new flavonoid derivatives, named pithecellobiumol A (1) and pithecellobiumol B (2) and 17 flavonoids (3-19). Their structures were elucidated based on 1D and 2D-NMR spectra as well as HR-ESI-MS data. The absolute configurations of new compounds were assigned by comparing their experimental specific rotation or ECD curves with the calculated data. The inhibitory activity on Aβ aggregation was screened by ThT assay, and compounds 7 (70.7%), 9 (86.5%), 10 (88.4%), 15 (86.1%) and 16 (87.7%) showed outstanding inhibition rate at 20μM compared to the positive control, curcumin (65.64%). In addition, docking study was performed to initially examine possible molecular mechanisms. Considering the important role of oxidative stress in AD, all the isolated compounds were tested for their H2O2-induced damage in human neuronblastoma SH-SY5Y cells. Among them, compound 16 (91.0%) was the most potent candidate in the treatment of AD.

Lignans from the seeds of Chinese hawthorn (Crataegus pinnatifida var. major N.E.Br.) against β-amyloid aggregation

Abstract Phytochemical investigation on the seeds of hawthorn (Crataegus spp.) led to the isolation of a new compound, (7′R, 8′R, 8S)-isolariciresinol (1), along with six known compounds (2–7). The structures of all compounds were determined based on spectroscopic data interpretation. The Aβ1–42 inhibition activity of all isolated compounds was evaluated in vitro. As a result, compounds 5 and 6 showed stronger inhibition of Aβ1–42 aggregation than curcumin, with inhibition rates of 70.59 and 68.14% at 20 μM. The possible mechanism of interaction between Aβ1–42 and the active compounds 5 and 6 was also investigated by molecular docking.

Alkaloids with neuroprotective effects from the leaves of Isatis indigotica collected in the Anhui Province, China

Six undescribed alkaloids, indiforine A-F, together with four known ones, were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated on the basis of extensive spectroscopic analyses. The absolute configurations of indiforine A and B were determined by comparison of the experimental and calculated electronic circular dichroism spectra, as well as experimental and calculated optical rotations. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that in H2O2-induced SH-SY5Y cell injury models, indiforine A and B exhibited potent neuroprotective activities. Further investigation of the most potent indiforine A by Hoechst 33258 staining and Annexin V/PI analysis demonstrated that it could protect SH-SY5Y cells from oxidative damage through inhibiting cell apoptosis.

Enantiomeric neolignans from Picrasma quassioides exhibit distinctive cytotoxicity on hepatic carcinoma cells through ROS generation and apoptosis induction

Three pairs of enantiomeric neolignans 1a/1b-3a/3b were isolated from the stems of Picrasma quassioides, and separated successfully by chiral-phase HPLC. Their structures were established by comprehensive spectroscopic analyses as well as ECD spectroscopy. The in vitro cytotoxicity of the isolates was evaluated against human hepatocellular carcinoma HepG2 and Hep3B cells. Among them, 1 and its enantiomers 1a/1b, 3 and 3a/3b displayed similar cytotoxicity in pair-wise comparison against HepG2 and Hep3B cells, and the similar effects of 2 and 2a/2b were found in Hep3B cells. Interestingly, 2a and 2b had different cytotoxic activities on HepG2 cells with IC50 values of 35.6u202fμM and 104.4u202fμM, respectively. In addition, 2 exerted middle cytotoxicity against HepG2 cells with an IC50 value of 78.6u202fμM. The different cytotoxicity between enantiomers 2a and 2b attracted our interest. To investigate the underlying mechanisms responsible for the distinct cytotoxicity, we further assessed the effects of 2a and 2b on cell cycle distribution, cell apoptosis and reactive oxygen species (ROS) generation. The results indicated that 2a had more significant effect than 2b on apoptosis induction and ROS generation, but both had no obvious effect on cell cycle of HepG2 cells. It is concluded that the different configurations of 2a/2b determined the enantioselective cytotoxicity on HepG2 cells through apoptosis induction and ROS generation.

Synthesis of new sarsasapogenin derivatives with antiproliferative and apoptotic effects in MCF-7 cells

Graphical abstract Figure. No caption available. HighlightsNew sarsasapogenin derivatives were synthesized and evaluated for their cytotoxicity.The structure‐activity relationship was investigated.Compound 4c exhibited the greatest cytotoxic activity against MCF‐7 cell line.Compound 4c inhibited the colony formation and induced the apoptosis of MCF‐7 cells.The mitochondrial pathway was involved in the compound 4c‐mediated apoptosis. ABSTRACT Sarsasapogenin, a kind of mainly effective component of Anemarrhena asphodeloides Bunge, possesses good antitumor properties. Two series of new sarsasapogenin derivatives were synthesized and evaluated for their cytotoxicities against three human cancer cell lines (HepG2, A549, MCF‐7) using the MTT assay. The structure‐activity relationship revealed that the N, N‐dimethylamino, pyrrolidinyl, and imidazolyl substituted at the C26 position could increase the antitumor efficacy of the 3‐oxo sarsasapogenin series of compounds. Compound 4c with pyrrolidinyl substituted at the C26 position exhibited the greatest cytotoxic activity against MCF‐7 cell line (IC50 = 10.66 &mgr;M), which was 4.3‐fold more potent than sarsasapogenin. Action mechanism investigations showed that 4c could inhibit the colony formation and induce the apoptosis of MCF‐7 cells. Further researches showed that a decrease in mitochondrial membrane potential and increases in the expression level of cleaved‐PARP and the ratio of Bax/Bcl‐2 were observed in MCF‐7 cells after treatment with 4c, suggesting that the mitochondrial pathway was involved in the 4c‐mediated apoptosis. These results show that compound 4c may serve as a lead for further optimization.

Two new sesquineolignans from the seeds of Crataegus pinnatifida and their β-amyloid aggregation inhibitory activitiy

Abstract Two new sesquineolignans, hawthornsesquinins K and L (1 and 2), were isolated from the seeds of Crataegus pinnatifida. Their structures were determined by spectroscopic analyses, including 1D, 2D NMR and HRESIMS data. All isolated compounds were tested for their β-amyloid aggregation inhibitory activity and neuroprotective effects against H2O2-induced damage in SH-SY5Y cells. The results indicated that compound 1 showed prominent inhibition of Aβ1–42 aggregation and significant neuroprotective effect on H2O2-induced cellular damage in SH-SY5Y cells.

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

Abstract 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.

Network pharmacology-based screening of the active ingredients and potential targets of the genus of Pithecellobium marthae (Britton & Killip) Niezgoda & Nevl for application to Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of β-amyloid (Aβ), and neuronal loss. Given the prevalence of AD and the lack of effective long-term therapies, there is a pressing need to discover viable leads that can be developed into clinically approved drugs with disease-modifying effects. The analysis of current reported literatures confirms the importance of the plants of Pithecellobium genus as candidate against AD. Hence, it is necessary to identify selective anti-dementia agents from this genus. To explore potential compounds with marked effect on AD in Pithecellobium genus, a compound database based on the methods of network pharmacology prediction was established in this paper by constructing the compound-disease target network. The result showed that the most effective compound in the plants of this genus might be (7′R,8′R)-7′-methoxyl strebluslignanol, and the most potential target might be Macrophage colony-stimulating factor 1 receptor.

ent-Kaurane Diterpenoids with Neuroprotective Properties from Corn Silk (Zea mays)

Thirteen new ent-kaurane diterpenoids, stigmaydenes A-M (1-13), together with two known compounds (14, 15), were isolated from the crude extract of corn silk ( Zea mays). The structures of the compounds were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was defined by single-crystal X-ray diffraction. The absolute configurations of the compounds were also confirmed by comparison of experimental and calculated specific rotations. The compounds were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury, and compound 8 was active at 100 μM, as determined by flow cytometry (annexin V-FITC/PI staining) and Hoechst 33258 staining. The results suggested that compound 8 could protect neuronal cells from H2O2-induced injury by inhibiting apoptosis in SH-SY5Y cells.

Investigation of chemical constituents of safflower and their tyrosinase inhibitory activity

Abstract Investigation on bioactive chemical constituents of safflower led to the isolation of 10 compounds from the aqueous extract, including a new alkaloid (1), a new glucopyranoside (2), and 8 known compounds (3–10). The structures of two new compounds were elucidated on the basis of extensive spectral analyses, including 1D, 2D-NMR and HRESIMS. Biological research on the isolates indicated that compounds 3, 4 and 9 remarkably inhibited tyrosinase with IC50 at 0.11, 0.20 and 0.11 mM, respectively, compared with the positive control arbutin (0.26 mM). To investigate the interaction between enzyme and isolated compounds, an in silico docking study was carried out. The research provided valuable experience for phytochemistry and biological investigation on safflower.