Huperzine A injection ameliorates motor and cognitive abnormalities via regulating multiple pathways in a murine model of Parkinson's disease

Guo, Xinran; Wu, Yuxin; Wang, Qingqing; Zhang, Jianbing; Sheng, Xueping; Zheng, Lan-rong; Wang, Yule

doi:10.1016/j.ejphar.2023.175970

Cited by 11 publications

(4 citation statements)

References 58 publications

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“…After seeding for 24 h, HepG2 cells (2.5 × 10 6 cells/well) were treated with PA (0.4 μM) and MY17 (2–20 μM) for 24 h, followed by treatment with insulin (100 nM) for 10 min. After harvesting, HepG2 cells were lysed with cell lysis buffer, and the protein concentration was measured by BCA protein quantification kit. , Each protein sample was detected by Western blotting using the corresponding primary antibody and secondary antibody. , …”

Section: Methodsmentioning

confidence: 99%

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Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity

Li,

Min

et al. 2024

J. Med. Chem.

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Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4dione derivatives (MY1−41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1−41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC 50 ) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 μM, compared with that of the positive control lithocholic acid (IC 50 = 9.62 ± 0.14 μM). The most potent compound, MY17 (IC 50 = 0.41 ± 0.05 μM), was a reversible, noncompetitive inhibitor of PTP1B. Circular dichroism spectroscopy and molecular docking were employed to analyze the binding interaction between MY17 and PTP1B. In HepG2 cells, MY17 treatment could alleviate palmitic acid (PA)-induced insulin resistance by upregulating the expression of phosphorylated insulin receptor substrate and protein kinase B. In vivo, oral administration of MY17 could reduce the fasting blood glucose level and improve glucose tolerance and dyslipidemia in mice suffering from DM.

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Section: Methodsmentioning

confidence: 99%

“…After harvesting, HepG2 cells were lysed with cell lysis buffer, and the protein concentration was measured by BCA protein quantification kit. 43,44 Each protein sample was detected by Western blotting using the corresponding primary antibody and secondary antibody. 45,46 4.7.…”

Section: Methodsmentioning

confidence: 99%

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity

Li,

Min

et al. 2024

J. Med. Chem.

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“…The administration of huperzine A, a plant-derived lycopodium alkaloid acting as a natural acetylcholinesterase inhibitor, improved the memory and learning ability of MPTPinduced murine models of PD, which was accompanied by the prevention of dopaminergic degeneration and the modulation of inflammatory and apoptotic mechanisms [82].…”

Section: Huperzine Amentioning

confidence: 99%

Cognitive Impairment in Parkinson’s Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches

Degirmenci,

Angelopoulou,

Georgakopoulou

et al. 2023

Medicina

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Cognitive impairment in patients with Parkinson’s disease (PD) is one of the commonest and most disabling non-motor manifestations during the course of the disease. The clinical spectrum of PD-related cognitive impairment includes subjective cognitive decline (SCD), mild cognitive impairment (MCI) and PD dementia (PDD). As the disease progresses, cognitive decline creates a significant burden for the family members and/or caregivers of patients with PD, and has a great impact on quality of life. Current pharmacological treatments have demonstrated partial efficacy and failed to halt disease progression, and novel, effective, and safe therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, the improvement of mitochondrial function, the regulation of synaptic plasticity, an impact on the gut–brain axis, the modulation of neuroinflammation and the upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment.

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“…Moreover, administration of huperzine A, a plant-derived lycopodium alkaloid acting as a natural acetylcholinesterase inhibitor, was able to improve memory and learning ability of MPTPinduced murine models of PD, which was accompanied by prevention of dopaminergic degeneration, and modulation of inflammatory and apoptotic mechanisms [71].…”

Section: Agents For Pdd Under Investigation: An Update On Preclinical...mentioning

confidence: 99%

Cognitive Impairment in Parkinson’s Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches

Degirmenci,

Angelopoulou,

Georgakopoulou

et al. 2023

Preprint

View full text Add to dashboard Cite

Cognitive impairment in patients with Parkinson’s disease (PD), which may occur in various severities, represents one of the commonest and most disabling non-motor manifestations during the course of the disease, causing a negative impact on patients’ quality of life. Eventually, it becomes a burden for the family members and/or the caregivers of patients, as it progresses to PD dementia. Current pharmacological treatments for cognitive impairment in PD exhibit partial efficacy, while novel effective therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline, and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, improvement of mitochondrial function, regulation of synaptic plasticity, impact on gut-brain axis, modulation of neuroinflammation, upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this overview, we aim to cover the clinical aspects of PD associated cognitive impairment, highlighting recent evidence on emerging treatment approaches that are currently under investigation at a preclinical and clinical level.

show abstract

Huperzine A injection ameliorates motor and cognitive abnormalities via regulating multiple pathways in a murine model of Parkinson's disease

Cited by 11 publications

References 58 publications

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity

Cognitive Impairment in Parkinson’s Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches

Cognitive Impairment in Parkinson’s Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches

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