Inhibition of Src tyrosine kinase activity by squamosamide derivative FLZ attenuates neuroinflammation in both in vivo and in vitro Parkinson's disease models

Tai, Wenjiao; Ye, Xuan; Bao, Xiaoyong; Zhao, Bin; Wang, Xiaoliang; Zhang, Dan

doi:10.1016/j.neuropharm.2013.07.020

Cited by 43 publications

(37 citation statements)

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“…FLZ is a novel synthesized compound that can cross the blood -brain barrier and reach neocortex and hippocampus [4]. Consistent with the data that FLZ inhibited microglia activation and suppressed cytokine release in LPS-induced PD rat models [7], our results clearly showed that administration of FLZ downregulated reactive gliosis by reducing pro-inflammatory molecules and cytokine production. Combination with previous studies demonstrated that FLZ is a potent reagent for the treatment of AD [5,6], and the anti-inflammatory effect of FLZ provided additional evidence for its therapeutic potential in AD.…”

Section: Discussionsupporting

confidence: 88%

“…The neuroprotective effects of FLZ had been well documented in Ab-induced AD mouse models [5] and APP/PS1 double-transgenic mice [6]. Moreover, FLZ also showed strong anti-inflammatory property in lipopolysaccharide (LPS)-induced Parkinson's disease (PD) rat models [7] and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models [8]. However, whether the neuroprotective effects of FLZ on AD are associated with its anti-inflammatory property remains unclear and needs to be demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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FLZ attenuates learning and memory deficits via suppressing neuroinflammation induced by LPS in mice

Bao

Pang

et al. 2015

Journal of Asian Natural Products Research

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Alzheimer's disease (AD) is the most common neurodegenerative disorder in which neuroinflammation plays an important role. FLZ is a novel synthetic derivative of natural squamosamide. Previous studies demonstrated that FLZ had neuroprotective effects on AD models and showed strong anti-inflammatory property in Parkinson's disease models. However, whether the neuroprotective effects of FLZ on AD are associated with its anti-inflammatory property is still not fully elucidated. In this study, we aimed to investigate the ability of FLZ in modulating inflammation. The results showed that FLZ significantly improved memory deficits and alleviated neuronal damage as well as neuronal loss in the hippocampus of mice intracerebroventricular injected with lipopolysaccharide (LPS). Mechanistic studies revealed that the neuroprotective effects of FLZ were due to the suppression of neuroinflammation induced by LPS, as indicated by inactivation of astrocytes and microglia, reduced production of tumor necrosis factor-α, interleukin-1β, and nitric oxide, as well as decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase. The beneficial effects of FLZ on AD were further supported by the finding that FLZ attenuated β-amyloid production through inhibiting β-amyloid precursor protein cleaving enzyme 1 expression. These results suggested that anti-inflammatory agent could be useful for the treatment of AD.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

FLZ attenuates learning and memory deficits via suppressing neuroinflammation induced by LPS in mice

Bao

Pang

et al. 2015

Journal of Asian Natural Products Research

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“…The apomorphine-induced rotational test was used to estimate the injury degree of dopaminergic system [29]. Apomorphine-induced rotation cycles signifcantly increased in the model group rats induced by intranigral injection of LPS, in contrast, PLA treatment showed an improvement effect on this behavioral dysfunction (Fig.…”

Section: Discussionmentioning

confidence: 99%

Alkaloids from piper longum protect dopaminergic neurons against inflammation-mediated damage induced by intranigral injection of lipopolysaccharide

Guo

et al. 2016

BMC Complement Altern Med

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BackgroundAlkaloids from Piper longum (PLA), extracted from P. longum, have potent anti-inflammatory effects. The aim of this study was to investigate whether PLA could protect dopaminergic neurons against inflammation-mediated damage by inhibiting microglial activation using a lipopolysaccharide (LPS)-induced dopaminergic neuronal damage rat model.MethodsThe animal behaviors of rotational behavior, rotarod test and open-field test were investigated. The survival ratio of dopaminergic neurons and microglial activation were examined. The dopamine (DA) and its metabolite were detected by high performance liquid chromatography (HPLC). The effects of PLA on the expression of interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and nitric oxide (NO) were also estimated.ResultsWe showed that the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and DA content in the striatum were reduced after a single intranigral dose of LPS (10 μg) treatment. The survival rate of TH-ir neurons in the SNpc and DA levels in the striatum were significantly improved after treatment with PLA for 6 weeks. The over-activated microglial cells were suppressed by PLA treatment. We also observed that the levels of inflammatory cytokines, including TNF-α, IL-6 and IL-1β were decreased and the excessive production of ROS and NO were abolished after PLA treatment. Therefore, the behavioral dysfunctions induced by LPS were improved after PLA treatment.ConclusionThis study suggests that PLA plays a significant role in protecting dopaminergic neurons against inflammatory reaction induced damage.

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“…Importantly, the squamosamide derivative FLZ showed enhanced antioxidant activity; in APP-SH-SY5Y expressing cells it selectively inhibited "-secretase activity without Qin et al 2011;Fang and Liu 2008;Bao et al 2012Bao et al , 2013Tai et al 2013) …”

Section: Annona Glabraissquamosamide Derivative (Flz Compound)mentioning

confidence: 99%

Brain Food for Alzheimer-Free Ageing: Focus on Herbal Medicines

Hügel

2015

Advances in Experimental Medicine and Biology

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Healthy brain aging and the problems of dementia and Alzheimer's disease (AD) are a global concern. Beyond 60 years of age, most, if not everyone, will experience a decline in cognitive skills, memory capacity and changes in brain structure. Longevity eventually leads to an accumulation of amyloid plaques and/or tau tangles, including some vascular dementia damage. Therefore, lifestyle choices are paramount to leading either a brain-derived or a brain-deprived life. The focus of this review is to critically examine the evidence, impact, influence and mechanisms of natural products as chemopreventive agents which induce therapeutic outcomes that modulate the aggregation process of beta-amyloid (Aβ), providing measureable cognitive benefits in the aging process. Plants can be considered as chemical factories that manufacture huge numbers of diverse bioactive substances, many of which have the potential to provide substantial neuroprotective benefits. Medicinal herbs and health food supplements have been widely used in Asia since over 2,000 years. The phytochemicals utilized in traditional Chinese medicine have demonstrated safety profiles for human consumption. Many herbs with anti-amyloidogenic activity, including those containing polyphenolic constituents such as green tea, turmeric, Salvia miltiorrhiza, and Panax ginseng, are presented. Also covered in this review are extracts from kitchen spices including cinnamon, ginger, rosemary, sage, salvia herbs, Chinese celery and many others some of which are commonly used in herbal combinations and represent highly promising therapeutic natural compounds against AD. A number of clinical trials conducted on herbs to counter dementia and AD are discussed.

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Inhibition of Src tyrosine kinase activity by squamosamide derivative FLZ attenuates neuroinflammation in both in vivo and in vitro Parkinson's disease models

Cited by 43 publications

References 37 publications

FLZ attenuates learning and memory deficits via suppressing neuroinflammation induced by LPS in mice

FLZ attenuates learning and memory deficits via suppressing neuroinflammation induced by LPS in mice

Alkaloids from piper longum protect dopaminergic neurons against inflammation-mediated damage induced by intranigral injection of lipopolysaccharide

Brain Food for Alzheimer-Free Ageing: Focus on Herbal Medicines

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