Protective Effects of Wogonin against Alzheimer’s Disease by Inhibition of Amyloidogenic Pathway

Huang, Ding-Siang; Yu, Yu Chen; Wu, Chung Hsin; Lin, Jung‐Yaw

doi:10.1155/2017/3545169

Cited by 30 publications

(11 citation statements)

References 53 publications

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“…The results maybe due to other constituents had no significant inhibitory activity against AChE. Wogonin, one of the major active constituents in Scutellaria baicalensis Georgi, has been reported to had protective effects against AD by inhibition of amyloidogenic pathway ( Huang et al, 2017 ) and tau phosphorylation ( Zhu and Wang, 2015 ). The flavonoid baicalein, which is derived from Scutellaria baicalensis Georgi , is reported to have the ability of inhibiting GSK3β activity, reducing β-secretase enzyme (BACE1), decreasing the concentration of total Aβ, and preventing phosphorylation of tau in APP/PS1 mice (Gu Gu X.-H. et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer’s Disease

Shen¹,

Zhang²,

Pang³

et al. 2020

Front. Pharmacol.

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Alzheimer's disease (AD) has become a worldwide disease that is harmful to human health and brings a heavy economic burden to healthcare system. Xiao-Xu-Ming Decoction (XXMD) has been widely used to treat stroke and other neurological diseases for more than 1000 years in China. However, the synergistic mechanism of the constituents in XXMD for the potential treatment of AD is still unclear. Therefore, the present study aimed to predict the potential targets and uncover the material basis of XXMD for the potential treatment of AD. A network pharmacology-based method, which combined data collection, drug-likeness filtering and absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties filtering, target prediction and network analysis, was used to decipher the effect and potential targets of XXMD for the treatment of AD. Then, the acetylcholinesterase (AChE) inhibitory assay was used to screen the potential active constituents in XXMD for the treatment of AD, and the molecular docking was furtherly used to identify the binding ability of active constituents with AD-related target of AChE. Finally, three in vitro cell models were applied to evaluate the neuroprotective effects of potential lead compounds in XXMD. Through the China Natural Products Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, Traditional Chinese Medicine (TCM)-Database @Taiwan and literature, a total of 1481 compounds in XXMD were finally collected. After ADME/T properties filtering, 908 compounds were used for the further study. Based on the prediction data, the constituents in XXMD formula could interact with 41 AD-related targets. Among them, cyclooxygenase-2 (COX-2), estrogen receptor α (ERα) and AChE were the major targets. The constituents in XXMD were found to have the potential to treat AD through multiple AD-related targets. 62 constituents in it were found to interact with more than or equal to 10 AD-related targets. The prediction results were further validated by in vitro biology experiment, resulting in several potential anti-AD multitarget-directed ligands (MTDLs), including two AChE inhibitors with the IC50 values ranging from 4.83 to 10.22 μM. Moreover, fanchinoline was furtherly found to prevent SH-SY5Y cells from the cytotoxicities induced by sodium nitroprusside, sodium dithionate and potassium chloride. In conclusion, XXMD was found to have the potential to treat AD by targeting multiple AD-related targets and canonical pathways. Fangchinoline and dauricine might be the potential lead compounds in XXMD for the treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer’s Disease

Shen¹,

Zhang²,

Pang³

et al. 2020

Front. Pharmacol.

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“…As described in our previous experiment [ 21 ], SH-SY5Y cells were cultured in a 1 : 1 mixture of Dulbecco's Modified Eagle's Medium and Ham's Nutrient Mixture F-12 with 100 μ g/mL streptomycin, 100 U/mL penicillin, and 10% fetal bovine serum (Thermo Fisher Scientific™). The SH-SY5Y cell culture medium was replaced every 48 hours, and cells were grown at 37°C in the presence of 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Chinese Veterinary Medicine B307 Promotes Cardiac Performance and Skeletal Muscle Contraction via Enhancing Intracellular Calcium Levels and Neural Electrical Activity in Animal and Cell Models

Lien

Hsu

et al. 2020

Evidence-Based Complementary and Alternative Medicine

Self Cite

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The study mainly investigated the effects of Chinese veterinary medicine B307 in cardiac and motor functions in animal models of pigeons and mice. Related cellular mechanisms were also studied in the neuroblastoma cell model of SH-SY5Y. Cardiac functions of pigeons and mice were examined by using moorFLPI Laser color Doppler imager and M-mode echocardiography, and motor functions were examined by using muscle electrical stimulation and force recording in the isolated breast muscle. Intracellular calcium levels and electrical activity of SH-SY5Y cells were examined by using Fura 2-AM fluorescence and MED64 system separately. Our results in vivo found that those pigeons under oral B307 treatment obviously enhanced subcutaneous microcirculation and contractile force and prolonged fatigue time in their breast muscles. Those mice under oral B307 treatment obviously elevated ejection fraction and cardiac output in their hearts. Our results in vitro showed that those SH-SY5Y cells under B307 treatment obviously increased intracellular calcium mobilization and electrical activities. These results revealed that improvement of cardiac and motor functions under B307 treatments may be caused by increasing electrical activities and intracellular calcium levels in neuromuscular cells and a similar mechanism may also occur in muscle cells. Thus, we suggested that B307 can be a functional Chinese veterinary medicine for flying pigeons.

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“…Therefore, all these compounds have been investigated as potential therapeutics to treat mitochondrial dysfunctions characterizing many neurodegenerative diseases. When administered in vitro in AD and ALS cell lines, these compounds can significantly increase cell survival, reducing oxidative stress and restoring MMP [139,151,[217][218][219]; likewise, preclinical studies in vivo on AD and ALS models confirmed their neuroprotective effects, improving cognitive functions and delaying motor symptom onset and disease progression, respectively [73,139,151,220]. Furthermore, the first promising results on human clinical trials have appeared: in fact, curcumin was effective in lifespan elongation and in decreasing disease progression in ALS patients, although the low oral bioavailability makes new delivery methods necessary [151]; and resveratrol has shown to be safe, tolerable, and effective in mitigating cognitive decline in clinical trials on AD patients (NCT01504854 [221]; NCT00678431 [222]).…”

Section: Compounds Targeting Multiple Mitochondrial Dysfunctionsmentioning

confidence: 99%

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

Stanga

Caretto

Boido

et al. 2020

IJMS

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Mitochondria play a central role in a plethora of processes related to the maintenance of cellular homeostasis and genomic integrity. They contribute to preserving the optimal functioning of cells and protecting them from potential DNA damage which could result in mutations and disease. However, perturbations of the system due to senescence or environmental factors induce alterations of the physiological balance and lead to the impairment of mitochondrial functions. After the description of the crucial roles of mitochondria for cell survival and activity, the core of this review focuses on the “mitochondrial switch” which occurs at the onset of neuronal degeneration. We dissect the pathways related to mitochondrial dysfunctions which are shared among the most frequent or disabling neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, Amyotrophic Lateral Sclerosis, and Spinal Muscular Atrophy. Can mitochondrial dysfunctions (affecting their morphology and activities) represent the early event eliciting the shift towards pathological neurobiological processes? Can mitochondria represent a common target against neurodegeneration? We also review here the drugs that target mitochondria in neurodegenerative diseases.

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Protective Effects of Wogonin against Alzheimer’s Disease by Inhibition of Amyloidogenic Pathway

Cited by 30 publications

References 53 publications

Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer’s Disease

Network Pharmacology-Based Analysis of Xiao-Xu-Ming Decoction on the Treatment of Alzheimer’s Disease

Chinese Veterinary Medicine B307 Promotes Cardiac Performance and Skeletal Muscle Contraction via Enhancing Intracellular Calcium Levels and Neural Electrical Activity in Animal and Cell Models

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

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