Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats

Zeng, Kuan; Li, Mengzhu; Hu, Jichang; Mahaman, Yacoubou Abdoul Razak; Bao, Jing; Huang, Fang; Xia, Yiyuan; Liu, Xinghua; Wang, Qun; Wang, Jian‐Zhi; Yang, Yang; Liu, Rong; Wang, Xiao-Chuan

doi:10.2174/1567205014666170829102135

Cited by 62 publications

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“…Till now, a number of natural plant extracts have shown the ability to reduce tau hyperphosphorylation and the formation of Aβ deposits. We have found that Moringa oleifera (MO), Tamarix gallica (TG), Codonopsis pilosula polysaccharide (CPPs) and Ginkgo biloba extract EGb761 can attenuate memory deficits in AD animal model [83][84][85][86] . These natural plant extracts have the ability to decrease tau phosphorylation and increase PP2A activity but the exact mechanism is unclear.…”

Section: Natural Plant Extractsmentioning

confidence: 99%

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

et al. 2020

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Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes. As a confirmed tumor suppressor, PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells. In the brains of Alzheimer's disease (AD) patients, decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and Aβ generation. In this review, we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD. The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed. It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.

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Section: Natural Plant Extractsmentioning

confidence: 99%

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

et al. 2020

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“…Tau phosphorylation is one of the two hallmarks of AD. Hcy was reported to induce tau hyperphosphorylation in rats [ 24 ] as well as exacerbating tau and Aβ pathology in AD animal model [ 21 ]. As an antioxidant MO might modulate the Hcy induced tau hyperphosphorylation.…”

Section: Resultsmentioning

confidence: 99%

“…4A-J ). Recently we found PP2A is inactivated by Hcy through increased Try307 phosphorylation [ 24 ]. Here in, the total PP2A protein level was not affected ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, there is an urgent need for drugs with multiple effects and therefore naturally occurring phytochemicals with neuroprotective, anti-amyloidogenic, antioxidative and anti-inflammatory properties, which are characteristics of MO as well, could be a possible way out [ 45 ]. Extracts like EGb761 and HSS-888 have already shown antioxidative, anti-tau hyperphosphorylation and anti-Aβ potentials [ 24, 46 ]. Moreover, phytoconstituents like heptanol, Trans-linaloloxide and Linalool oxide in MO, have a good permeability of blood-brain barrier with low toxicity [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

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Moringa Oleifera Alleviates Homocysteine-Induced Alzheimer’s Disease-Like Pathology and Cognitive Impairments

Mahaman

Huang

et al. 2018

JAD

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Alzheimer’s disease (AD) is multifactorial with unclear etiopathology. Due to the complexity of AD, many attempted single therapy treatments, like Aβ immunization, have generally failed. Therefore, there is a need for drugs with multiple benefits. Naturally occurring phytochemicals with neuroprotective, anti-amyloidogenic, antioxidative, and anti-inflammatory properties could be a possible way out. In this study, the effect of Moringa oleifera (MO), a naturally occurring plant with high antioxidative, anti-inflammatory, and neuroprotective effects, was evaluated on hyperhomocysteinemia (HHcy) induced AD-like pathology in rats. Homocysteine (Hcy) injection for 14 days was used to induce AD-like pathology. Simultaneous MO extract gavage followed the injection as a preventive treatment or, after injection completion, MO gavage was performed for another 14 days as a curative treatment. MO was found to not only prevent but also rescue the oxidative stress and cognitive impairments induced by Hcy treatment. Moreover, MO recovered the decreased synaptic proteins PSD93, PSD95, Synapsin 1 and Synaptophysin, and improved neurodegeneration. Interestingly, MO decreased the Hyc-induced tau hyperphosphorylation at different sites including S-199, T-231, S-396, and S-404, and at the same time decreased Aβ production through downregulation of BACE1. These effects in HHcy rats were accompanied by a decrease in calpain activity under MO treatment, supporting that calpain activation might be involved in AD pathogenesis in HHcy rats. Taken together, our data, for the first time, provided evidence that MO alleviates tau hyperphosphorylation and Aβ pathology in a HHcy AD rat model. This and previous other studies support MO as a good candidate for, and could provide new insights into, the treatment of AD and other tauopathies.

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“…Moreover, several studies have shown that diets rich in antioxidants demonstrate neuroprotective effects against AD [ 9 , 37 , 38 ]. Curcumin [ 39 ], ginkgo biloba [ 40 ], and quercetin [ 9 , 10 , 20 ], all with antioxidative and anti-inflammatory activities, were shown to improve spatial learning and memory abilities by reducing the level of the AD biomarkers APP, BACE, or Tau protein.…”

Section: Discussionmentioning

confidence: 99%

Bioactive Compounds in Kimchi Improve the Cognitive and Memory Functions Impaired by Amyloid Beta

2018

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This study investigated the abilities of kimchi and its bioactive compounds to ameliorate amyloid beta (Aβ)-induced memory and cognitive impairments. Mice were given a single intracerebroventricular injection of Aβ25-35, followed by a daily oral administration of capsaicin (10 mg·kg-bw–1), 3-(4′-hydroxyl-3′,5′-dimethoxyphenyl)propionic acid (50 mg/kg bw), quercetin (50 mg/kg bw), ascorbic acid (50 mg/kg bw), or kimchi methanol extract (KME; 200 mg/kg bw) for 2 weeks (n = 7 per group). Carboxymethylcellulose was used as a vehicle for the normal and control groups. Behavioral task tests showed that the learning and memory abilities were significantly waned by the injected Aβ25-35, but these cognitive deficits were recovered by the administrated KME and kimchi bioactive compounds (p < 0.05). The reactive oxygen species, peroxynitrite, and thiobarbituric acid reactive substances levels were lower, and the glutathione level was higher, in the KME and bioactive compound groups than in the control group (p < 0.05). In the KME and bioactive compound groups, the protein expression levels of antioxidant enzymes (nuclear factor (erythroid-derived 2)-like 2-regulated superoxide dismutase-1 and glutathione peroxidase) were increased, whereas those of inflammation-related enzymes (nuclear factor-kappaB -regulated inducible nitric oxide synthase and cyclooxygenase-2) were decreased (p < 0.05). Thus, the antioxidative and anti-inflammatory properties of bioactive compounds-rich kimchi might help to attenuate the symptoms of Alzheimer’s disease.

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Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats

Abstract: EGb761 might be a promising drug to treat AD through its anti-oxidative activity and decreasing tau hyperphosphorylation besides the protection against the Aβ-induced neurotoxicity.

Cited by 62 publications

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Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

Moringa Oleifera Alleviates Homocysteine-Induced Alzheimer’s Disease-Like Pathology and Cognitive Impairments

Bioactive Compounds in Kimchi Improve the Cognitive and Memory Functions Impaired by Amyloid Beta

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