Tetramethylpyrazine Ameliorates Rotenone-Induced Parkinson’s Disease in Rats: Involvement of Its Anti-Inflammatory and Anti-Apoptotic Actions

Michel, Haidy E.; Tadros, Mariane G.; Esmat, Ahmed; Khalifa, Amani E.; Abdel‐tawab, Ahmed M.

doi:10.1007/s12035-016-0028-7

Cited by 72 publications

(31 citation statements)

References 87 publications

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“…Accumulation of α-synuclein in Lewy bodies is an key pathological event in PD and enhanced expression of α-synuclein influences neuronal death by either necrosis or apoptosis [ 42 ]. Moreover, impairment of autophagy results in accumulation of aggregated α-synuclein protein favoring neurodegeneration.…”

Section: Resultsmentioning

confidence: 99%

Valeric Acid Protects Dopaminergic Neurons by Suppressing Oxidative Stress, Neuroinflammation and Modulating Autophagy Pathways

Jayaraj

Azimullah

et al. 2020

IJMS

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Parkinson’s disease, the second common neurodegenerative disease is clinically characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) with upregulation of neuroinflammatory markers and oxidative stress. Autophagy lysosome pathway (ALP) plays a major role in degradation of damaged organelles and proteins for energy balance and intracellular homeostasis. However, dysfunction of ALP results in impairment of α-synuclein clearance which hastens dopaminergic neurons loss. In this study, we wanted to understand the neuroprotective efficacy of Val in rotenone induced PD rat model. Animals received intraperitoneal injections (2.5 mg/kg) of rotenone daily followed by Val (40 mg/kg, i.p) for four weeks. Valeric acid, a straight chain alkyl carboxylic acid found naturally in Valeriana officianilis have been used in the treatment of neurological disorders. However, their neuroprotective efficacy has not yet been studied. In our study, we found that Val prevented rotenone induced upregulation of pro-inflammatory cytokine oxidative stress, and α-synuclein expression with subsequent increase in vital antioxidant enzymes. Moreover, Val mitigated rotenone induced hyperactivation of microglia and astrocytes. These protective mechanisms prevented rotenone induced dopaminergic neuron loss in SNpc and neuronal fibers in the striatum. Additionally, Val treatment prevented rotenone blocked mTOR-mediated p70S6K pathway as well as apoptosis. Moreover, Val prevented rotenone mediated autophagic vacuole accumulation and increased lysosomal degradation. Hence, Val could be further developed as a potential therapeutic candidate for treatment of PD.

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Section: Resultsmentioning

confidence: 99%

Valeric Acid Protects Dopaminergic Neurons by Suppressing Oxidative Stress, Neuroinflammation and Modulating Autophagy Pathways

Jayaraj

Azimullah

et al. 2020

IJMS

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“…PD is the second most common neurodegenerative disease and is characterized by a loss of dopaminergic neurons . Some environmental risk factors, such as ROT and MPP + , are used as neurotoxins for evaluating potential neuroprotective strategies against apoptotic diseases like PD . For in vitro PD studies, the SH‐SY5Y human neuroblastoma cell line is frequently used as a cell model, because it exhibits many characteristics of dopaminergic neurons .…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Some environmental risk factors, such as ROT and MPP + , are used as neurotoxins for evaluating potential neuroprotective strategies against apoptotic diseases like PD. [26][27][28][29][30] For in vitro PD studies, the SH-SY5Y human neuroblastoma cell line is frequently used as a cell model, because it exhibits many characteristics of dopaminergic neurons. 31,32 In the present study, we demonstrated that both RBM3 and mild hypothermia protect SH-SY5Y cells from ROT-induced neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Cold‐inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling

Yang

Zhuang

et al. 2019

J Cellular Molecular Medi

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Mild hypothermia and its key product, cold‐inducible protein RBM3, possess robust neuroprotective effects against various neurotoxins. However, we previously showed that mild hypothermia fails to attenuate the neurotoxicity from MPP+, one of typical neurotoxins related to the increasing risk of Parkinson disease (PD). To better understand the role of mild hypothermia and RBM3 in PD progression, another known PD‐related neurotoxin, rotenone (ROT) was utilized in this study. Using immunoblotting, cell viability assays and TUNEL staining, we revealed that mild hypothermia (32°C) significantly reduced the apoptosis induced by ROT in human neuroblastoma SH‐SY5Y cells, when compared to normothermia (37°C). Meanwhile, the overexpression of RBM3 in SH‐SY5Y cells mimicked the neuroprotective effects of mild hypothermia on ROT‐induced cytotoxicity. Upon ROT stimulation, MAPK signalling like p38, JNK and ERK, and AMPK and GSK‐3β signalling were activated. When RBM3 was overexpressed, only the activation of p38, JNK and ERK signalling was inhibited, leaving AMPK and GSK‐3β signalling unaffected. Similarly, mild hypothermia also inhibited the activation of MAPKs induced by ROT. Lastly, it was demonstrated that the MAPK (especially p38 and ERK) inhibition by their individual inhibitors significantly decreased the neurotoxicity of ROT in SH‐SY5Y cells. In conclusion, these data demonstrate that RBM3 mediates mild hypothermia‐related neuroprotection against ROT by inhibiting the MAPK signalling of p38, JNK and ERK.

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“…In the light of theory of TCM, kidney deficiency is the basis of amnesia and other cognitive deficits, while phlegm and blood stasis are significant pathological factors. For this reason, amounts of experiments and trials have been carried out and shown specific effects against cognitive decline, which involve Alpiniae oxyphyllae fructus [27], Ligusticum wallichii [28][29][30], curcuma [31][32], Fructus gardenia [33][34], Radix notoginseng [35][36]. Meanwhile, an herbal formula named Yi-Zhi-An-Shen (YZAS) Granules has been composed of Lophatherum gracile and medical herbs mentioned above, which is designed for aiding the treatment of cognitive deficits.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Yi-Zhi-An-Shen Granules on cognition and sleep quality in older adults with amnestic mild cognitive impairment: protocol for a randomized, double-blind, placebo-controlled trial

Yue

et al. 2019

Preprint

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BackgroundAmnestic mild cognitive impairment (aMCI) is a syndrome characterized by significant forgetfulness that does not meet the criteria of dementia. Individuals with aMCI are at a bigger risk of progressing to dementia. Current studies suggest good sleep quality is linked with preserved cognition in the elderly, and sleep complaints are common among the elderly with amnesia. Therefore, improving their sleep may be helpful for maintaining and improving their cognitive capacity. According to the theory of traditional Chinese medicine, Yi-Zhi-An-Shen is an herbal compound which may ameliorate forgetfulness and sleep disorders. As growing evidence indicates that gut microbiome is associated with major mental symptoms, a hypothesis was proposed that Yi-Zhi-An-Shen Granules (YZASG) might work by alternating microbial abundance and diversity. In this study, the investigators intend to assess the efficacy of YZASG on global cognition in the elderly suffering from aMCI, and evaluate its safety as well as its potential mechanisms via sleep quality, fecal microbial 16SrDNA and metagenomics analyses, and serum markers. Methods/designThis is a randomized, double-blind, placebo-controlled clinical trial. A total of 80 patients (aged 60~85 years) will be recruited and allocated randomly to a treatment group and a placebo group in a 1:1 ratio, then will be administered YZASG or isodose placebo three times a day. The intervention course is 16 weeks, with an 18-month follow-up. The primary outcome is Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-cog11). Secondary outcome measures are mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Pittsburgh Sleep Quality Index (PSQI), serum concentrations of immunological factors and inflammatory cytokines, fecal microbiota. Fecal microbiota will only be collected at the baseline and endpoint of the intervention. DiscussionThe results of this trial will be conducive to assessing the safety and effectiveness on cognition of YZASG in intervening aMCI among the elderly and determining if it takes effect via the improvement of sleep quality, regulation of gut microbita, concentration of certain serum markers. 4

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Tetramethylpyrazine Ameliorates Rotenone-Induced Parkinson’s Disease in Rats: Involvement of Its Anti-Inflammatory and Anti-Apoptotic Actions

Cited by 72 publications

References 87 publications

Valeric Acid Protects Dopaminergic Neurons by Suppressing Oxidative Stress, Neuroinflammation and Modulating Autophagy Pathways

Valeric Acid Protects Dopaminergic Neurons by Suppressing Oxidative Stress, Neuroinflammation and Modulating Autophagy Pathways

Cold‐inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling

Effectiveness of Yi-Zhi-An-Shen Granules on cognition and sleep quality in older adults with amnestic mild cognitive impairment: protocol for a randomized, double-blind, placebo-controlled trial

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