Hederagenin and α-hederin promote degradation of proteins in neurodegenerative diseases and improve motor deficits in MPTP-mice

Wu, An-Guo; Zeng, Wu; Wong, Vincent Kam Wai; Zhu, Yi‐Zhun; Lo, Amy Cheuk Yin; Liu, Liang; Law, Betty Yuen‐Kwan

doi:10.1016/j.phrs.2016.11.002

Cited by 50 publications

(39 citation statements)

References 87 publications

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“…Therefore, pharmacological intervention of the autophagic pathway can be a promising therapeutic strategy for a variety of pathological conditions. For example, the well-known mammalian target of rapamycin (mTOR) inhibitor rapamycin, and recently identified active autophagic herbal compounds onjisaponin B (Wu et al, 2013), neferine (Wong et al, 2015), hederagenin and α-hederin (Wu et al, 2017), can induce the mTOR-dependent autophagy with an accelerated clearance of mutant huntingtin fragments in Huntington's disease models (Ravikumar et al, 2004). Carbamazepine, an autophagy enhancer, was shown to ameliorate α1-antitrypsin deficiency disorder (Hidvegi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms

et al. 2017

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Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes. In addition, tetrandrine induces cell death in a panel of apoptosis-resistant cell lines that are deficient for caspase 3, caspase 7, caspase 3 and 7, or Bax-Bak respectively. We also showed that tetrandrine-induced cell death is independent of necrotic cell death. Mechanistically, tetrandrine induces autophagy that depends on mTOR inactivation. Furthermore, tetrandrine induces autophagy in a calcium/calmodulin-dependent protein kinase kinase-β (CaMKK-β), 5′ AMP-activated protein kinase (AMPK) independent manner. Finally, by kinase profiling against 300 WT kinases and computational molecular docking analysis, we showed that tetrandrine is a novel PKC-α inhibitor, which lead to autophagic induction through PKC-α inactivation. This study provides detailed insights into the novel cytotoxic mechanism of an anti-tumor compound originated from the herbal plant, which may be useful in promoting autophagy mediated- cell death in cancer cell that is resistant to apoptosis.

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Section: Introductionmentioning

confidence: 99%

Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms

et al. 2017

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“…Trametenolic acid could significantly improve learning and memory ability of the cerebral ischemia injury rats [32]. Wu et al found that Hederagenin could be used as a novel autophagic enhancer to play a role in neuroprotection by improving motor deficits in Parkinson's disease mice model [33]. Stigmasterol could ameliorate memory impairment and promotes neuritogenesis and synaptogenesis [34].…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology-based study on Alzheimer disease prevention and treatment of Qiong Yu Gao

You

Chen

et al. 2020

BioData Mining

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Background and objective: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. Methods: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. Results: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. Conclusion: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

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“…Trametenolic acid could significantly improve learning and memory ability of the cerebral ischemia injury rats 33 . Wu et al found that Hederagenin could be used as novel autophagic enhancer to play a role in neuroprotection by improving motor deficits in Parkinson's disease mice model 34 . Stigmasterol could ameliorate memory impairment and promotes neuritogenesis and synaptogenesis 35,36 .…”

Section: Discussionmentioning

confidence: 99%

“…And compound-target-disease network for the 4 herbs were constructed, respectively (RR-Targets, Figure 2A; PC-Targets, Figure 2B; PG-Targets, Figure 2C and AC-Targets, Figure 2D). The results revealed that 14 major ingredients in RR, 15 in PC, 34 in PG and 7 in AC may play important roles in anti-AD.…”

Section: Network Construction Of the Anti-ad Targets Of Qygmentioning

confidence: 92%

A Network Pharmacology-Based Study on Alzheimer disease prevention and treatment of Qiong Yu Gao

You

Chen

et al. 2020

Preprint

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Background and objective: As the pathological mechanisms of AD is complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. Methods: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. Results: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. KEGG pathway enrichment analysis found that three signaling pathways were closely related with AD treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. Conclusion: This study demonstrated that QYG exerted the effect of treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

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Hederagenin and α-hederin promote degradation of proteins in neurodegenerative diseases and improve motor deficits in MPTP-mice

Cited by 50 publications

References 87 publications

Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms

Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms

A network pharmacology-based study on Alzheimer disease prevention and treatment of Qiong Yu Gao

A Network Pharmacology-Based Study on Alzheimer disease prevention and treatment of Qiong Yu Gao

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