INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 19
·11572
·
IF 6.208
Chengzhao Li,Jun Dang,Yue Lv,Yan Fang,Chengjun Ma,Qilan Wang,Gang Li
Dracocephalum heterophyllum(D. heterophyllum) is a traditional Chinese Tibetan medicine that has been used for the treatment of lymphitis, hepatitis, and bronchitis. However, only a few selected chemical components are currently obtained fromD. heterophyllum, which limits its further pharmacological applications. In this study, we have obtained samwinol fromD. heterophyllumby medium- and high-pressure liquid chromatography separation for the first time. Thereafter, we investigated the protective actions of samwinol against amyloid beta protein fragment 25–35 (Aβ25–35) induced neurotoxicity in cultured rat pheochromocytoma PC-12 cells and explored its underlying mechanisms of action. The results indicated that samwinol could increase cell viability and inhibit the production of reactive oxygen species (ROS) and mitochondria-derived ROS, as assessed by MTT assay, Giemsa staining, and flow cytometry assay. Through Western blot analysis, it was found that samwinol substantially inhibited the phosphorylation of ERK(1/2) and promoted the expression of HO-1 and Nrf2. The data obtained from molecular docking were also consistent with the above conclusions. All of these results showed that samwinol fromD. heterophyllumcan display significant anti-neuroinflammatory and antioxidant activities in vitro, which are associated with the suppression of ERK/AKT phosphorylation and the activation of the Nrf2/HO-1 signaling pathway. In the future, additional in-depth mechanism studies will be carried out to provide more evidence for the potential of samwinol in the treatment of Alzheimer’s disease.Keywords:D. heterophyllum;PC-12 Cells;Aβ25–35;neuroinflammatory;oxidative stress
研究领域:
药理学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
BRAIN RESEARCH
·
2025
·
IF 2.6
Xiao-Han Ma,Hui Dai,Song-Yao Liu,Xiao-Na Liu,Jing Zhang,Xue-Lian Meng
Glutamate (Glu) excitotoxicity and amyloid-β (Aβ) deposition are significant factors in the occurrence and development of Alzheimer’s disease (AD). Dauricine and daurisoline are two alkaloid components of Menispermum dauricum DC . that have a protective effect on the nervous system. The protection of dauricine and daurisoline on Glu-injured PC12 cells and the protection dauricine on Aβ 25-35 -injured PC12 cells were investigated in this study. The results of the study demonstrated that on PC12 cells damaged by Glu (20 mM), dauricine and daurisoline (3 and 10 μM) increased the cell viability, reduced cell apoptosis, and enhanced mitochondrial membrane potential (MMP) levels. Dauricine and daurisoline can also reduce the levels of intracellular ROS and free Ca 2+ , and suppression the expression of CaM, p-CaMKII, and p-Tau in Glu-damaged PC12 cells. In addition, on PC12 cells damaged by Aβ 25-35 (30 μM), dauricine (3 and 10 μM) can also significantly increase the cell viability and MMP levels, inhibit cell apoptosis, reduce intracellular ROS and free Ca 2+ levels, and down-regulate protein expression of CaM, p-CaMKII, and p-Tau. This study demonstrates for the first time that dauricine and daurisoline may inhibit the excessive phosphorylation of Tau protein and subsequent cell apoptosis by suppressing the Ca 2+ -CaM/CaMKII pathway, thereby protecting PC12 cells damaged Glu or Aβ 25-35 in vitro . Dauricine and daurisoline have the potential to treat AD effectively and have further research value.
研究领域:
神经生物学
·
药理学
·
阿尔茨海默病研究
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Jing Han,Haotian Zhang,Yu Zhang,Zan Zhang,Maomao Yu,Sijie Wang,Fei Han
Ethnopharmacological relevance Alzheimer's disease (AD) is recognized as one of the most prevalent neurodegenerative diseases . Lingguizhugan decoction (LGZGD) is a classical traditional Chinese medicine (TCM). Many studies have shown that LGZGD can alleviate the symptoms of AD. Aim of the study The aim of this study was to assess the neuroprotective effects of LGZGD and elucidate its molecular mechanism on Aβ 25-35 -induced PC12 cells. Materials and methods PC12 cells were used MTT assays, ELISA , fluorescence probe analyses, Hoechst 33342 staining, immunofluorescent staining and western blot analyses were systematically conducted to evaluate the underlying mechanisms of LGZGD. Results In Aβ 25-35 -induced PC12 cells, LGZGD remarkably increased cell viability, reduced the generation of TNF-α, IL-1β, IL-6, MDA and ROS , increased the activity of GSH-Px, inhibited cell apoptosis , downregulated the expression of Bax and cleaved caspase-3, and upregulated the expression of Bcl-2. Moreover, LGZGD modulated the NF-κB/MAPK signaling pathways by upregulating the levels of IκBα and phospho-ERK, while downregulating the levels of phospho-p65, phospho-IκBα, and phospho-p38. Furthermore, LGZGD repressed the nuclear translocation activity of NF-κB p65. Meanwhile, LGZGD increased the expression of phospho-GSK-3β and reversed the hyperphosphorylation of Tau proteins by inhibiting the activation of the ERK MAPK pathway. Conclusions Taken together, the present study suggested that LGZGD may be a valuable drug candidate that can attenuate the neurotoxicity induced by Aβ 25-35 by modulating the NF-κB/MAPK signaling pathways in PC12 cells.
研究领域:
药理学
·
神经科学
·
中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MASS SPECTROMETRY
·
2020
·Vol. 55
·期 10
·e4643
·
IF 1.671
Bo Pang,Xiaoyu Zhuang,Xinyu Bian,Shu Liu,Zhiqiang Liu,Fengrui Song
A wealth of epidemiological evidence indicates a strong link between type 2 diabetes (T2D) and Alzheimer's disease (AD). The fiber deposition with cross-β-sheet structure formed by self-aggregation and misfolding of amyloidogenic peptides is a common hallmark of both diseases. For the patients with T2D, the fibrils are mainly found in the islets of Langerhans that results from the accumulation of human islet amyloid polypeptide (hIAPP). The major component of aggregates located in the brain of AD patients is amyloid-β (Aβ). Many biophysical and physiological properties are shared by hIAPP and Aβ, and both peptides show similar cytotoxic mechanisms. Therefore, it is meaningful to investigate the possible cross-interactions of hIAPP and Aβ in both diseases. In this article, the segment 25–35 of Aβ was selected because Aβ 25–35 was a core region in the process of amyloid formation and showed similar aggregation tendency and toxicity with full-length Aβ. The electrospray ionization-ion mobility-mass spectrometry analysis and thioflavin T fluorescence kinetic analysis combined with transmission electron microscopy were used to explore the effects of the coexistence of Aβ 25–35 and hIAPP on the self-aggregation of both peptides and whether there was co-assembly in fibrillation. The results indicated that the aggregation of hIAPP and Aβ 25–35 had two nucleation stages in the binary mixtures. hIAPP and Aβ 25–35 had a high binding affinity and a series of hetero-oligomers formed in the mixtures of hIAPP and Aβ 25–35 in the early stage. The cross-reaction between hIAPP monomers and Aβ 25–35 monomers as well as a little of oligomers during primary nucleation stage could accelerate the aggregation of Aβ 25–35 . However, owing to the obvious difference in aggregation ability between hIAPP and Aβ 25–35 , this cross-interaction had no significant impact on the self-assembly of hIAPP. Our study may offer a better understanding for exploring the molecular mechanism of the association between AD and T2D observed in clinical and epidemiological studies and developing therapeutic strategies against amyloid diseases.
研究领域:
生物化学
·
神经科学
·
糖尿病研究
·
阿尔茨海默病研究
✓ 已验证
DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2019
·
IF 3.407
Jialin Xu,Leilei Zhou,Qi Weng,Linxia Xiao,Qingyong Li
Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer's Disease (AD). In the present study, we adopted an vitro model that involved Aβ 25-35 -induced oxidative damage in PC12 cells. Aβ 25-35 (10 μΜ) treatment for 24 h induced significant cell death and oxidative stress in PC12 cells, as evidenced by cell viability reduction, LDH release, ROS accumulation and increased production MDA . (1E,4E)-1, 5-bis(4-hydroxy-3-methoxyphenyl) penta-1, 4-dien-3-one (CB) and (1E, 4E)-1-(3, 4-dimethoxyphenyl)-5-(4-hydroxy-3, 5-dime-thoxyphenyl) Penta-1, 4-dien-3-one (FE), two Curcumin (Cur) analogues displayed neuroprotective effects against Aβ 25-35 -induced oxidative damage and cellular apoptosis in PC12 cells. Here, we investigated three different treatment ways of CB and FE. It was interesting that post-treatment of CB and FE (restoring way) showed similar effect to the preventive way, while attenuating way did not show any protective effect. We found that low dose CB and FE increased transcriptional factor NF-E2-related factor 2 (Nrf2)/hemo oxygenase 1 (HO-1) protein expression and decreased Kelch-like ECH-associated protein 1 (Keap1) in PC 12 cells. In addition, CB and FE promoted the translation of Nrf2 into nuclear and enhanced the activity of superoxide dismutase (SOD)/catalase, which confirmed cytoprotection against Aβ 25-35 -induced oxidative damage. Moreover, CB and FE could increase Bcl-2 expression level, decrease the level of Bax and Cyt-c in Aβ 25-35 -treated PC12 cells. Ultimately, the neuroprotective effect of CB and FE provides a pharmacological basis for its clinical use in prevention and treatment of AD.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2016
·Vol. 42
·期 4
·1073-1083
·
IF 2.472
Song Xiaoyu,Zhou Biao,Cui Lingyu,Lei Di,Zhang Pingping,Yao Guodong,Xia Mingyu,Hayashi Toshihiko,Hattori Shunji,Ushiki-Kaku Yuko,Tashiro Shin-ichi,Onodera Satoshi,Ikejima Takashi
Alzheimer’s disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aβ 25-35 -injected rats. Results demonstrated that silibinin significantly attenuated Aβ 25-35 -induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aβ 25-35 -injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ 25-35 -injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities.
研究领域:
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）