A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine

Chen, Hai Yun; Xu, Da; Tan, Guo Lian; Cai, Wei; Zhang, Gao Xiao; Cui, Wei; Wang, Jin Zhao; Long, Cheng; Sun, Ye; Yu, Pei; Tsim, Karl Wah-Keung; Zhang, Zai Jun; Han, Yifan; Wang, Yu Qiang

doi:10.1007/s12031-015-0566-x

Cited by 34 publications

(19 citation statements)

References 30 publications

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“…1F). It was chosen from a large library of derivatives based on phenotypic screening assays and bioavailability (Chen et al, 2015; Prior et al, 2013). Each group began the study with 10 animals.…”

Section: Resultsmentioning

confidence: 99%

A novel curcumin derivative for the treatment of diabetic neuropathy

et al. 2018

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Neuropathy is a common complication of long-term diabetes. Proposed mechanisms of neuronal damage caused by diabetes that are downstream of hyperglycemia and/or loss of insulin signaling include ischemic hypoxia, inflammation and loss of neurotrophic support. The curcumin derivative J147 is a potent neurogenic and neuroprotective drug candidate initially developed for the treatment of neurodegenerative conditions associated with aging that impacts many pathways implicated in the pathogenesis of diabetic neuropathy. Here, we demonstrate efficacy of J147 in ameliorating multiple indices of neuropathy in the streptozotocin-induced mouse model of type 1 diabetes. Diabetes was determined by blood glucose, HbA1c, and insulin levels and efficacy of J147 by behavioral, physiologic, biochemical, proteomic, and transcriptomic assays. Biological efficacy of systemic J147 treatment was confirmed by its capacity to decrease TNFα pathway activation and several other markers of neuroinflammation in the CNS. Chronic oral treatment with J147 protected the sciatic nerve from progressive diabetes-induced slowing of large myelinated fiber conduction velocity while single doses of J147 rapidly and transiently reversed established touch-evoked allodynia. Conduction slowing and allodynia are clinically relevant markers of early diabetic neuropathy and neuropathic pain, respectively. RNA expression profiling suggests that one of the pathways by which J147 imparts its protection against diabetic induced neuropathy may be through activation of the AMP kinase pathway. The diverse biological and therapeutic effects of J147 suggest it as an alternative to the polypharmaceutical approaches required to treat the multiple pathogenic mechanisms that contribute to diabetic neuropathy.

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Section: Resultsmentioning

confidence: 99%

A novel curcumin derivative for the treatment of diabetic neuropathy

et al. 2018

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“…Eight-day-old Sprague-Dawley rats were obtained from the Experimental Animal Center of Sun Yat-sen University. The detailed methodology used to separate the CGNs is described in our previous publication ( Chen H.Y. et al, 2015 ).…”

Section: Methodsmentioning

confidence: 99%

A Novel Tetramethylpyrazine Derivative Protects Against Glutamate-Induced Cytotoxicity Through PGC1α/Nrf2 and PI3K/Akt Signaling Pathways

et al. 2018

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Glutamate-induced excitotoxicity is one of the main causes of neuronal cell death in stroke. Compound 22a has been previously reported as a promising neuroprotective compound derived from tetramethylpyrazine, which is a widely used active ingredient of traditional Chinese medicine Chuanxiong (Ligusticum wallichii Franchat). Compound 22a can protect neurons from oxidative stress-induced PC12 cell death and alleviates the infarct areas and brain edema in a rat permanent middle cerebral artery occlusion model. In the current work, we further investigated the neuroprotective effects and underlying mechanisms of compound 22a against glutamate-induced excitotoxicity in primary culture of rat cerebellar granule neurons (CGNs). We found that pretreatment with compound 22a prevented glutamate-induced neuronal damage by maintaining mitochondrial membrane potential and attenuating cellular apoptosis. Compound 22a could also enhance peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) transcriptional activity and induce nuclear accumulation of Nrf2 in PC12 cells. Accordingly, pretreatment with compound 22a reversed the glutamate-induced down-regulation of expression of the proteins PGC1α, transcriptional factor NF-E2-related factor 2 (Nrf2), and hemooxygenase 1 (HO-1). In addition, compound 22a increased the phosphorylation of phosphoinositide 3-kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and glycogen synthase kinase 3β (p-GSK3β). Meanwhile, the small interfering RNA-mediated silencing of PGC1α expression and selective inhibitors targeting PI3K/Akt (LY294002 and Akt-iv) could significantly attenuate the neuroprotective effect of compound 22a. Taken together, compound 22a protected against glutamate-induced CGN injury possibly in part through regulation of PGC1α/Nrf2 and PI3K/Akt pathways.

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“…TN-2, which has two nitrone moieties, also exhibited potent neuroprotective effects against 6-OHDA-induced neurotoxicity and MPTP/MPP + -induced dopaminergic neurons damage [73, 74]. Another derivative of TMP, known as T-006 (Figure 2), protected primary cortical neurons from neurotoxicity as well as improvement in memory deficits in APP/PS1 transgenic mice [75]. …”

Section: Therapeutic Implications For Vci With Traditional Chinesementioning

confidence: 99%

Vascular Contributions to Cognitive Impairment and Treatments with Traditional Chinese Medicine

Zhou

Cui

Tseng

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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The prevalence of cognitive impairment and dementia caused by cerebrovascular disease is likely to increase with the global aging population. Vascular contributions to cognitive impairment and dementia (VCID) is a wide spectrum term used to include a diverse heterogeneous group of cognitive syndromes with vascular factors regardless of the cause of pathogenesis. VCID ranges from mild cognitive impairment to full-blown dementia with vascular dementia (VaD) as the most severe stage. It is further complexed by the coexistence of other forms of dementia such as Alzheimer's disease (AD). Recent researches in the functions of the neurovascular unit (NVU) suggest that dysfunction of the NVU might be the cause of primary vascular events in the brain that leads to further neurodegeneration. In this review, we have briefly summarized various forms of VCID. There is currently no standard therapy for VCID or dementia. Given the fact that Traditional Chinese Medicine (TCM) has gained popularity worldwide, we also reviewed recent scientific and clinical findings on various antidementia TCM for the treatment of VCID, including Salvia miltiorrhiza, Huperzia serrata, Ligusticum chuanxiong, Ginkgo biloba, Panax ginseng, and also TCM formula Sailuotong capsule (SLT) and Fufangdanshen tablets (FFDS).

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A Potent Multi-functional Neuroprotective Derivative of Tetramethylpyrazine

Cited by 34 publications

References 30 publications

A novel curcumin derivative for the treatment of diabetic neuropathy

A novel curcumin derivative for the treatment of diabetic neuropathy

A Novel Tetramethylpyrazine Derivative Protects Against Glutamate-Induced Cytotoxicity Through PGC1α/Nrf2 and PI3K/Akt Signaling Pathways

Vascular Contributions to Cognitive Impairment and Treatments with Traditional Chinese Medicine

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