Tetramethylpyrazine reverses intracerebroventricular streptozotocin-induced memory deficits by inhibiting GSK-3&amp;beta;

Lu, Fanghong; Xu, Li; Li, Wei; Wei, Ke; Yao, Yong; Zhang, Qianlin; Liang, Xinliang; Zhang, Jiewen

doi:10.1093/abbs/gmx059

Cited by 26 publications

(15 citation statements)

References 28 publications

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“…42 A close relationship exists between impairment in behavioral function and disruption of neurotransmitters homeostasis in hippocampus in AD as well as in experimental animals. 43,44 Linked with this, these alterations in hippocampal neurochemistry following ICV-STZ infusion in rats in the present study. On the other hand, significant alterations in hippocampal neurochemistry including deficits in monoamines (NE, DA and 5HT) and disturbed balance of GABA and Glutamate have also been reported to occur in AD 45,46 as well as following ICV-STZ infusion in rats.…”

Section: Discussionsupporting

confidence: 72%

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Rimpi

Deshmukh

2020

IJPI

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Background: With the constant failure of the clinical trials and continuous exploration of a therapeutic target against Alzheimer's disease (AD) is the utmost needed. Chebulinic acid (ChA) has been reported to possess neuroprotective potential in various neurodegenerative models such as anxiety and depression. Materials and Methods: In the current study, the ChA was challenged on the progression of AD induced by intracerebroventricular (ICV)-streptozotocin (STZ)-induced neurotoxicity to determine its therapeutic potential in experimental dementia. STZ was infused bilaterally (3 mg/kg/icv) on day 1 st and 3 rd after surgery. ChA (25, 50 and 100 mg/kg/p.o) was administered from 7 th day onwards up to 21 st day following 1 st ICV-STZ infusion. Cognitive impairment was evaluated by actophotometer, Morris water maze (MWM) and object recognition task (ORT) in rats whereas biochemical, neurochemical, neuroinflammatory were evaluated using hipoocampal brain regions on day 22 nd. Results: Ventricular administration of STZ in rats found to significantly shorten the latency time on the MWM and ORT which was associated with significant alterations in hippocampal biochemistry, including elevation in oxidative stress and compromised antioxidant defense, neurotransmitter alteration and elevation in neuroinflammatory cytokine levels. ChA treatment significantly prevented the ICV-STZ-induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and compromised antioxidant defense and cholinergic deficits in rats. Conclusion: These results clearly pointed to the pivotal role of ChA in ICV-STZ induced neurotoxicity and its association may be a promising alternative to be investigated in the treatment of AD-like dementia.

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Section: Discussionsupporting

confidence: 72%

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Rimpi

Deshmukh

2020

IJPI

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“…To investigate the basis of compositions against AD, we searched the previous literature for these 9 ingredients and surprisingly found that 6 of them were confirmed to possess anti-AD effects (Table 2 ). For instance, tetramethylpyrazine (TMP), one of the major bioactive compounds purified from CX, shows great potential against AD, which could restore the function of cholinergic neurons and protect against memory loss in AD rat model [ 65 ]. Besides, ligustilide was reported to have neuroprotective effect via inducting α-Secretase processing of both APP and Klotho in AD mouse [ 66 ].…”

Section: Resultsmentioning

confidence: 99%

Systems pharmacology-based approach to investigate the mechanisms of Danggui-Shaoyao-san prescription for treatment of Alzheimer’s disease

Chen

et al. 2020

BMC Complement Med Ther

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Background Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, characterized by a progressive and irreversible loss of memory and cognitive abilities. Currently, the prevention and treatment of AD still remains a huge challenge. As a traditional Chinese medicine (TCM) prescription, Danggui-Shaoyao-san decoction (DSS) has been demonstrated to be effective for alleviating AD symptoms in animal experiments and clinical applications. However, due to the complex components and biological actions, its underlying molecular mechanism and effective substances are not yet fully elucidated. Methods In this study, we firstly systematically reviewed and summarized the molecular effects of DSS against AD based on current literatures of in vivo studies. Furthermore, an integrated systems pharmacology framework was proposed to explore the novel anti-AD mechanisms of DSS and identify the main active components. We further developed a network-based predictive model for identifying the active anti-AD components of DSS by mapping the high-quality AD disease genes into the global drug-target network. Results We constructed a global drug-target network of DSS consisting 937 unique compounds and 490 targets by incorporating experimental and computationally predicted drug–target interactions (DTIs). Multi-level systems pharmacology analyses revealed that DSS may regulate multiple biological pathways related to AD pathogenesis, such as the oxidative stress and inflammatory reaction processes. We further conducted a network-based statistical model, drug-likeness analysis, human intestinal absorption (HIA) and blood-brain barrier (BBB) penetration prediction to uncover the key ani-AD ingredients in DSS. Finally, we highlighted 9 key ingredients and validated their synergistic role against AD through a subnetwork. Conclusion Overall, this study proposed an integrative systems pharmacology approach to disclose the therapeutic mechanisms of DSS against AD, which also provides novel in silico paradigm for investigating the effective substances of complex TCM prescription.

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“…For example, it is stated that the activation of GSK-3β is closely related to aluminum-induced long-term potentiation injury in rats ( 8 ). Others have shown that tetramethylpyrazine can protect the memory loss of AD patients by inhibiting GSK-3β activity ( 9 ). In recent years, studies have also found that there is a certain regulatory relationship between GSK-3β and miR.…”

Section: Introductionmentioning

confidence: 99%

Effects of regulating miR-132 mediated GSK-3β on learning and memory function in mice

et al. 2020

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The aim f of this study was to explore effects of miR-132 and glycogen synthase kinase-3β (GSK-3β) on learning and memory in mice. miR-132 inhibitor GSK-3β overexpression agent (sh-GSK-3β) and normal saline (negative control group) were injected into the hippocampus of adult mice, and healthy adult mice were taken as the unrelated control group. The expression of miR-132 and GSK-3β in the hippocampus of adult and elderly mice was detected using reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Morris water maze test was employed to detect learning and memory function in mice. The dual luciferase reporter was adopted to determine the relationship between miR-132 and GSK-3β. Compared with the adult group, the expression of miR-132 was significantly downregulated in the hippocampus in the elderly group, while the expression of GSK-3β was upregulated. Injecting miR-132 inhibitor into the hippocampus of adult mice led to a significant increase in escape latency and a significant decrease in the number of times of crossing platforms. The injection of GSK-3β overexpression agent into the hippocampus of adult mice resulted in a marked increase in escape latency and a significant decrease in the number of times of crossing platforms in the water maze test. It was also found that downregulation of GSK-3β reversed the decline in learning and memory in mice caused by downregulation of miR-132 expression. The dual luciferase report identified a targeted regulatory relationship between miR-132 and GSK-3β. Overexpression of miR-132 can inhibit the expression of GSK-3β in mouse learning and memory ability, which provides some inspiration for understanding the occurrence of learning and memory disorders and future treatment methods.

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Tetramethylpyrazine reverses intracerebroventricular streptozotocin-induced memory deficits by inhibiting GSK-3β

Cited by 26 publications

References 28 publications

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Chebulinic Acid Negated the Development of Streptozotocin- Induced Experimental Dementia in Rats

Systems pharmacology-based approach to investigate the mechanisms of Danggui-Shaoyao-san prescription for treatment of Alzheimer’s disease

Effects of regulating miR-132 mediated GSK-3β on learning and memory function in mice

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