20C, a bibenzyl compound isolated from Gastrodia elata, protects PC12 cells against rotenone-induced apoptosis via activation of the Nrf2/ARE/HO-1 signaling pathway

Huang, Juyang; Yuan, Yu‐He; Yan, Jiaqing; Wang, Yanan; Chu, Shifeng; Zhu, Cheng‐Gang; Guo, Qing‐Lan; Shi, Jian‐Gong; Chen, Nai‐Hong

doi:10.1038/aps.2015.154

Cited by 55 publications

(31 citation statements)

References 36 publications

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“…Undifferentiated PC12 cells were cultured in DMEM complete medium with 10% heat-inactivated horse serum, 5% fetal bovine serum, 100 U/mL penicillin, and 100 μg/mL streptomycin and maintained at 37 °C in a humidified incubator supplemented with 5% CO 2 . To induce differentiation [13] , PC12 cells were seeded at a density of 2×10 4 cells/mL on a poly-L-lysine-coated 96-well plate and cultured in complete medium containing 2.5 ng/mL NGF or different concentrations of ARDD (0.1, 1, 10 μmol/L) concomitant with 2.5 ng/mL NGF administration. Four days after incubation, morphometric analysis was performed on digitized images of live cells taken under phase contrast illumination with an inverted microscope linked to a camera.…”

Section: Methodsmentioning

confidence: 99%

The natural product 4,10-aromadendranediol induces neuritogenesis in neuronal cells in vitro through activation of the ERK pathway

Chang

Ruan

et al. 2016

Acta Pharmacol Sin

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Recent studies focus on promoting neurite outgrowth to remodel the central nervous network after brain injury. Currently, however, there are few drugs treating brain diseases in the clinic by enhancing neurite outgrowth. In this study, we established an NGF-induced PC12 differentiation model to screen novel compounds that have the potential to induce neuronal differentiation, and further characterized 4,10-Aromadendranediol (ARDD) isolated from the dried twigs of the Baccharis gaudichaudiana plant, which exhibited the capability of promoting neurite outgrowth in neuronal cells in vitro. ARDD (1, 10 μmol/L) significantly enhanced neurite outgrowth in NGF-treated PC12 cells and N1E115 cells in a time-dependent manner. In cultured primary cortical neurons, ARDD (5, 10 μmol/L) not only significantly increased neurite outgrowth but also increased the number of neurites on the soma and the number of bifurcations. Further analyses showed that ARDD (10 μmol/L) significantly increased the phosphorylation of ERK1/2 and the downstream GSK-3β, subsequently induced β-catenin expression and up-regulated the gene expression of the Wnt ligands Fzd1 and Wnt3a in neuronal cells. The neurite outgrowth-promoting effect of ARDD in neuronal cells was abolished by pretreatment with the specific ERK1/2 inhibitor PD98059, but was partially reversed by XAV939, an inhibitor of the Wnt/β-catenin pathway. ARDD also increased the expression of BDNF, CREB and GAP-43 in N1E115 cells, which was reversed by pretreatment with PD98059. In N1E115 cells subjected to oxygen and glucose deprivation (OGD), pretreatment with ARDD (1-10 μmol/L) significantly enhanced the phosphorylation of ERK1/2 and induced neurite outgrowth. These results demonstrated that the natural product ARDD exhibits neurite outgrowth-inducing activity in neurons via activation of the ERK signaling pathway, which may be beneficial to the treatment of brain diseases.

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Section: Methodsmentioning

confidence: 99%

The natural product 4,10-aromadendranediol induces neuritogenesis in neuronal cells in vitro through activation of the ERK pathway

Chang

Ruan

et al. 2016

Acta Pharmacol Sin

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“…Bcl-2 family proteins, which consist of the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2, are essential regulators of mitochondrion-mediated apoptosis [38]. Moreover, caspase-3 activation plays an imperative role in the release of cytochrome c from the mitochondrial membrane to the cytosol [39]. Our findings indicated that Daph significantly enhanced the expression of the Bcl-2 protein, reduced the expression of the Bax protein, and displayed a decrease of cleavagecaspase-3 production and a concomitant increase of pro-caspase-3 in t-BHP-treated RAW 264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death

Liu

Zhou

et al. 2017

Free Radical Biology and Medicine

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Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio. Further investigation indicated that Daph significantly suppressed cytochrome c release and NLRP3 inflammasome activation and modulated apoptosis-related protein Bcl-2, Bax, and caspase-3 expression. Moreover, Daph dramatically induced the expression of the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1), which is largely dependent on upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element (ARE) promoter activity. Additionally, Daph remarkably activated a c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation, but ERK and JNK inhibitor pretreatment exhibited an evident decrease of the level of Daph-enhanced Nrf2 nuclear translocation. Furthermore, Daph exposure suppressed t-BHP-induced cytotoxicity and ROS overproduction, which are mostly blocked in Nrf2 knockout RAW 264.7 cells and peritoneal macrophages. Accordingly, Daph exhibited protective roles against t-BHP-triggered oxidative damage and mitochondrial dysfunction by the upregulation of Nrf2 antioxidant signaling pathways, which may be involved in the activation of JNK and ERK.

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“…It is recorded that Gastrodiae Rhizoma has the functions of resting wind and relieving spasmodic, calming liver and inhibiting yang, dispelling wind and relaxing channels and collaterals [1]. Modern pharmacological research has shown that Gastrodiae Rhizoma has the effects of neuroregulation [19,20], neuroprotection [21][22][23][24], improving memory [28,29] and so on. It has auxiliary therapeutic effect on Alzheimer's disease (AD) [28] and Parkinson's disease (PD) [7,8,21,23] which are the common degenerative diseases nowadays.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis reveals underlying immune response mechanism of fungal (Penicillium oxalicum) disease in Gastrodia elata Bl. f. glauca S. Chow (Orchidaceae)

Wang

Gao

Zang

et al. 2020

Preprint

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Background: Gastrodia elata Bl. f. glauca S. Chow is a medicinal plant. G. elata f. glauca is unavoidably infected by pathogens in their growth process. In previous work, we have successfully isolated and identified Penicillium oxalicum from fungal diseased tubers of G. elata f. glauca . As a widespread epidemic, this fungal disease seriously affected the yield and quality of G. elata f. glauca . We speculate that the healthy G. elata f. glauca might carry resistance genes , which can resist against fungal disease. In this study, healthy and fungal diseased mature tubers of G. elata f. glauca from Changbai Mountain area were used as experimental materials to help us find the potential resistance genes against fungal disease. Results: A total of 7540 differentially expressed Unigenes (DEGs) were identified (FDR<0.01, log2FC>2). The current study screened 10 potential resistance genes. They were attached to transcription factors (TFs) in plant hormone signal transduction pathway and plant pathogen interaction pathway, including WRKY22, GH3, TIFY/JAZ, ERF1, WRKY33, TGA. In addition, four of these genes were closely related to jasmonic acid signaling pathway. Conclusions: The immune response mechanism of fungal disease in G. elata f. glauca is a complex biological process, involving plant hormones such as ethylene, jasmonic acid, salicylic acid and disease-resistant transcription factors such as WRKY, TGA.

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20C, a bibenzyl compound isolated from Gastrodia elata, protects PC12 cells against rotenone-induced apoptosis via activation of the Nrf2/ARE/HO-1 signaling pathway

Cited by 55 publications

References 36 publications

The natural product 4,10-aromadendranediol induces neuritogenesis in neuronal cells in vitro through activation of the ERK pathway

The natural product 4,10-aromadendranediol induces neuritogenesis in neuronal cells in vitro through activation of the ERK pathway

Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death

Transcriptome analysis reveals underlying immune response mechanism of fungal (Penicillium oxalicum) disease in Gastrodia elata Bl. f. glauca S. Chow (Orchidaceae)

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