Search

Chemical investigation of the EtOAc extract of the plant-associated fungus Alternaria alternate in rice culture led to the isolation of a novel liphatic polyketone, alternin A (1), a new indole alkaloid (8), and a new sesquiterpene (11), together with 12 known compounds. Their structures were elucidated by the interpretation of extensive spectroscopic data, and the absolute configurations of 1-3 were established using calculations of ECD spectra, NMR data, and optical rotation values. Compound 1 possesses an unprecedented C25 liphatic polyketone skeleton. Compounds 5 and 10 exhibited potential cytotoxic activities against MCF-7 and HepG cells, and compounds 2, 7, and 9 exhibited potential neuroprotective activities in glutamate induced-PC12 injured cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Three hiherto unknown phenylpropanoid compounds, namely (7S,8R)-1-(1-ethoxy-2-hydroxypropyl)-2-methoxy-3,4-(methylenedioxy)benzene (1), (7S,8S)-1-(1-ethoxy-2-hydroxypropyl)-2-methoxy-3,4-(methylenedioxy)benzene (2), and (7S,8R)-1-(1-methoxy-2-hydroxypropyl)-2-methoxy-3,4-(methylenedioxy)benzene (3), along with 12 known compounds (4 - 15) were obtained from the extract of whole plant of Chloranthus anhuiensis. Among them, 7 and 13 were obtained from nature for the first time. The structures of these natural compounds were characterized by extensive spectroscopic analysis and calculated electronic circular dichroism (ECD) data. Furthermore, their cytotoxic and neuroprotective activities were evaluated using MDA-MB-231, 4T1, HepG2, and PC12 cell lines. Compounds 8 and 13 exhibited moderate cytotoxic activities against MDA-MB-231 cell line with the IC 50 values of 39.7 and 25.8 μm, respectively. And all the isolated compounds have no neuroprotective activities., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

Glutamate-induced excitotoxicity plays a vital role in neurodegenerative diseases. Neuroprotection against excitotoxicity has been considered as an effective experimental approach for preventing and/or treating excitotoxicity-mediated diseases. In the present study, six new sesquiterpenoids (1-6) and 26 known compounds of this type (7-32) were isolated and characterized from the whole plants of Chloranthus anhuiensis. Chlorantolide A (1) is the first example of a 5,6- seco-germacrane-type sesquiterpenoid, while phacadinane E (2) is a rare 4,5- seco-cadinane-type sesquiterpenoid. The structures of the new compounds were determined by spectroscopic analysis and by calculations of electronic circular dichroism (ECD) spectra. Their neuroprotective effects in mediating glutamate-induced PC12 cell apoptosis were evaluated. Compound 26 exhibited potent neuroprotective activity with an EC 50 value of 3.3 ± 0.9 μM. Using Hoechst 33258 staining, a caspase-3 activity assay, and Western blot analysis it was demonstrated that this compound reduces the apoptosis of PC12 cells through inhibition of caspase-3 activity, while activating the Akt signaling pathway.

Oxidative stress, a predominant cause of apoptosis cascades triggered in neurodegenerative disorders, has been regarded as a critical inducement in the pathogenesis of Alzheimer's disease (AD). Gou Teng-San (GTS) is a traditional Chinese herbs preparation commonly utilized to alleviate cognitive dysfunction and psychological symptoms of patients with dementia. The present study aimed to investigate the protective effects of GTS40, an active fraction of GTS, on H 2 O 2 -induced oxidative damage and identify the potential active ingredients. Our results revealed that GTS40 exhibited radical scavenging activity, elevated cell viability, decreased the levels of intracellular reactive oxygen species (ROS), and stabilized mitochondrial transmembrane potential (MMP) in H 2 O 2 -treated PC12 cells. In addition, GTS40 blocked the apoptotic cascade by reversing the imbalance of Bcl-2/Bax and inhibiting the activity of caspase-3. Furthermore, an HPLC-QTOFMS method was developed to characterize major chemical constituents in GTS40. Our results revealed twenty-seven identified or tentatively characterized compounds through comparing their retention time (t R ) and MS spectra with reference standards. These results suggested that GTS40 was a promising active fraction that may be beneficial in the prevention and treatment of oxidative stress-mediated neurodegenerative disorders., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

In our previous study, we have elucidated the chemical profile of YGS40, a fraction of Yi-Gan San (YGS), used for the treatment of Alzheimer's disease (AD). Oxidative stress-induced apoptosis is implicated in neurodegenerative disorders such as AD. The aim of the present study was to explore the protective effects of YGS40 against hydrogen peroxide (H2O2)-induced apoptosis in PC12 cells and the underlying mechanisms. PC12 cells were exposed to 100 μmol·L(-1) of H2O2 for 12 h with or without YGS40 pretreatment. Cytotoxicity was determined by MTT (3, (4, 5-dimethylthiazole-2-yl) 2, 5-diphenyl-tetrazolium bromide) and lactate dehydrogenase (LDH) release assays; apoptosis was detected by Annexin V/propidium iodide coupled staining and by determining caspase-3 activity and Bax and Bcl-2 protein levels. Mitochondrial membrane potential (MMP) was assessed by the retention of rhodamine123; and the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured using commercially available enzymatic kits. Pretreatment with YGS40 significantly prevented H2O2-induced cytotoxicity and protected the cells against H2O2-triggered apoptosis characterized by externalization of membrane phosphatidylserine and caspase-3 activation and the increased ratio of Bax/Bcl-2 in PC12 cells. Further studies showed that YGS40 suppressed H2O2-induced MMP loss, increased SOD activity, and decreased MDA level. These findings suggest that YGS40 may be beneficial for the prevention and treatment of oxidative stress-mediated disorders., (Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Yi-Gan San (YGS), a traditional Chinese medicine for dementia-related symptoms, was previously fractionated. One active fraction, YGS40 exhibited a neuroprotective effect against glutamate-induced cytotoxicity. In the present study, high-performance liquid chromatography, coupled with diode-array detection and quadrupole time-of-flight mass spectrometry, was applied for the identification of its chemical constituents and for quantification studies. The chemical profile of YGS40 consisted of sixty-four identified or tentatively characterized compounds. The levels of the major marker compounds increased significantly in the mixed decoction compared with those in the single plant decoction. The results suggest the high precision of the analyses of most of the constituents in YGS40 and establish the quantitative variations of the major marker compounds between the single and mixed decoction processes., (Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background: Hypoxia appears in a number of extreme environments, including high altitudes, the deep sea, and during aviation, and occurs in cancer, cardiovascular disease, respiratory failures and neurological disorders. Though it is well recognized that hypoxic preconditioning (HPC) exerts endogenous neuroprotective effect against severe hypoxia, the mediators and underlying molecular mechanism for the protective effect are still not fully understood. This study established a hippocampus metabolomics approach to explore the alterations associated with HPC. Methods: In this study, an animal model of HPC was established by exposing the adult BALB/c mice to acute repetitive hypoxia four times. Ultra-high liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) in combination with univariate and multivariate statistical analyses was employed to deciphering metabolic changes associated with HPC in hippocampus tissue. MetaboAnalyst 3.0 was used to construct HPC related metabolic pathways. Results: The significant metabolic differences in hippocampus between the HPC groups and control were observed, indicating that HPC mouse model was successfully established and HPC could caused significant metabolic changes. Several key metabolic pathways were found to be acutely perturbed, including phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, phenylalanine metabolism, glutathione metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, citrate cycle, and glycerophospholipid metabolism. Conclusion: The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the neuroprotective mechanism of HPC. [ABSTRACT FROM AUTHOR]