Pharmacological Basis for Use of <i>Armillaria mellea</i> Polysaccharides in Alzheimer’s Disease: Antiapoptosis and Antioxidation

An, Shengshu; Lü, Wei; Zhang, Yongfeng; Yuan, Qingxia; Wang, Di

doi:10.1155/2017/4184562

Cited by 39 publications

(34 citation statements)

References 35 publications

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“…Ach, dynamically controlled by AchE, is responsible for the storage and recovery of long-term memory ( 28 ). Previous studies demonstrated that Armillaria mellea and Amanita caesarea can improve AD-like behaviors via enhancing the levels of Ach and ChAT in the serum and brains of AlCl 3 - and D-gal induced AD mice ( 15 , 17 ). The data in the present study suggested that SC-mediated protection against AD may be associated with its regulation of cholinergic function.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis

Hu¹,

Teng

et al. 2018

Mol Med Report

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Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an L-glutamic acid (L-Glu)-damaged HT22 cell apoptosis model and an aluminum chloride plus D-galactose-induced AD mouse model. In L-Glu-damaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase-3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase-3 activity assay kit, and propidium iodide and Annexin V staining. Furthermore, SC suppressed the accumulation of intracellular reactive oxygen species (ROS), restored the dissipation of mitochondrial membrane potential, enhanced the expression of antiapoptotic proteins and reduced the expression of pro-apoptotic proteins, as determined by immunofluorescence assays and western blotting. In AD mice, SC enhanced vertical and horizontal movements in an autonomic activity test, and reduced the escape latency time in the water maze test. SC reduced the deposition of amyloid β1–42 (Aβ1-42) and the expression of phosphorylated-Tau in the hippocampus as determined by immunohistochemistry analysis, but enhanced the serum levels of Aβ1–42 of AD mice as determined by ELISA. ELISA analyses also revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of AD mice. The present study confirmed that the protective effects of SC in AD in vitro and in vivo are associated with its antioxidant and antiapoptotic properties.

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Section: Discussionmentioning

confidence: 99%

“…The cell culture medium was collected to measure the release of LDH using an in vitro Toxicology Assay kit [Cytotoxicity Detection Kit (LDH); Sigma-Aldrich; Merck KGaA], according to a previous study ( 14 ). A MTT assay (Sigma-Aldrich; Merck KGaA) was used to detect cell viability as previously described ( 15 ).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis

Hu¹,

Teng

et al. 2018

Mol Med Report

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“…A. mellea, an edible and medicinal fungus, has been reported to exhibit antioxidant and antitumor activities (Wu et al, 2012). Besides, some data reported its neuroprotective roles against degenerative disorders such as Alzheimer's diseases (An et al, 2017), and it's insulin resistance reductive effects have recently been proposed (Yang et al, 2019). Glutathione S-transferases assure efficient enzymatic conjugation of the main antioxidant molecule, GSH, to the reactive electrophiles making them more water-soluble and excetable.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Armillaria mellea (Vahl) P. Kumm’nın karaciğer glutatyon S-transferaz aktivitesi üzerine baskılayıcı etkileri

Kütük

Sadı

2020

Anatolian Journal of Botany

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Armillaria mellea (Vahl) P. Kumm. commonly-known as the honey fungus is an edible mushroom and its antioxidant, antitumor, neuroprotective, and insulin resistance reductive effects have been well-characterized. Glutathione S-transferases (GST) are the group of detoxification enzymes has a function to conjugate glutathione to the variety of electrophile, making them more water-soluble for excretion. Their inhibition or activation could have profound toxicological or clinical implications. This study is conducted to investigate the inhibitory effects of A. mellea on GST enzymes. Total GST activities were measured using glutathione and 1 chloro-2,4-dinitrobenzene as substrates spectrophotometrically, and enzyme kinetic studies were conducted to determine Vmax and Km values. Additionally, aqueous and methanolic extracts of A. mellea were tested to see how they modulate the kinetic parameters. Vmax for liver GST enzyme was calculated as 443.90 ± 11.52 U/mg, Km value for GSH, and CDNB were determined as 4.88 ± 0.53 mM and 10.43 ± 1.07 mM, respectively. The decrease in Vmax and the increase in Km values with A. mellea extracts demonstrated a mixed-type inhibitory mechanism. Methanolic extract inhibits the GSH-dependent GST activity much more than the CDNB-dependent activity, but aqueous extract mainly affects CDNB-dependent GST activity. In conclusion, A. mellea could suppress the hepatic GST enzymes that might have toxicological consequences such as reduced cellular detoxification of electrophilic xenobiotics as well as alleviated drug resistance in the treatment of several diseases.Özet: Armillaria mellea (Vahl) P. Kumm. yaygın olarak bal mantarı olarak bilinen yenilebilir bir mantardır ve antioksidan, antitümör, nöroprotektif ve insülin direncini azaltıcı etkileri iyi karakterize edilmiştir. Glutatyon S-transferazlar (GST), detoksifikasyon enzimlerinin bir grubudur ve glutatyonu çeşitli elektrofillere konjüge etme fonksiyonuna sahiptir. Bu işlem onları atılım için suda daha fazla çözünür hale getirir. GST enzimlerinin baskılanması veya aktive edilmesinin toksikolojik veya klinik etkileri olabilir. Bu çalışma A. mellea'nın GST'ler üzerindeki baskılayıcı etkilerini araştırmak için yapılmıştır. Toplam GST aktiviteleri, spektrofotometrik olarak glutatyon ve 1 kloro-2,4-dinitrobenzen substratları kullanılarak ölçülmüş, Vmax ve Km değerlerini belirlemek için enzim kinetiği çalışmaları yapılmıştır. Ek olarak, A. mellea'nın sulu ve metanolik özütleri, kinetik parametreleri nasıl modüle ettiklerini değerlendirmek için test edilmiştir. Karaciğer GST enzimi için Vmax 443,90±11,52 U/mg, GSH ve CDNB için Km değerleri sırasıyla 4,88±0,53 mM ve 10,43±1,07 mM olarak belirlenmiştir. A. mellea ekstreleri ile Vmax'daki azalma ve Km değerlerindeki artış, GST enziminin karışık tipte inhibisyon mekanizmasıyla baskılandığını göstermiştir. Metanolik ekstraktın GSH-bağımlı GST aktivitesini CDNB-bağımlı aktiviteden çok daha fazla inhibe ettiği, fakat su ekstraktlarının esas olarak CDNB-bağımlı GST aktivitesini baskıladığı gösterilmiştir. Sonu...

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“…As in our previous study [37], the paraffin-embedded brain sections were soaked in xylene, treated with an ethanol gradient (100%, 90%, 80%, 70%), and incubated with terminal deoxynucleotidyl transferase and Click-iT™ Plus (Catalog Nos. C10617, Invitrogen, Thermo Fisher Scientific, Waltham, MA, USA) according to the instructions supplied by the manufacturer for TUNEL staining.…”

Section: Terminal Deoxynucleotidyl Transferase-mediated Deoxyuridine mentioning

confidence: 99%

Neuroprotective effects of verbascoside against Alzheimer’s disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice

Wang

Cai

Wang

et al. 2020

J Neuroinflammation

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Background Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer’s disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid β (Aβ)1–42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. Methods U251 cells were co-incubated with 10 μM of Aβ1-42 and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aβ1-42-damaged U251 cells. Results In Aβ1-42-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aβ, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis. Conclusions The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.

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Pharmacological Basis for Use of Armillaria mellea Polysaccharides in Alzheimer’s Disease: Antiapoptosis and Antioxidation

Cited by 39 publications

References 35 publications

Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis

Pharmacological basis for application of scutellarin in Alzheimer's disease: Antioxidation and antiapoptosis

Armillaria mellea (Vahl) P. Kumm’nın karaciğer glutatyon S-transferaz aktivitesi üzerine baskılayıcı etkileri

Neuroprotective effects of verbascoside against Alzheimer’s disease via the relief of endoplasmic reticulum stress in Aβ-exposed U251 cells and APP/PS1 mice

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