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Hexahydrocurcumin Attenuates Neuronal Injury and Modulates Synaptic Plasticity in Chronic Cerebral Hypoperfusion in Rats

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Abstract

Dementia is the most common age-related problem due predominantly to Alzheimer’s disease (AD) and vascular dementia (VaD). It has been shown that these contributors are associated with a high amount of oxidative stress that leads to changes in neurological function and cognitive impairment. The aim of study was to explore the mechanism by which hexahydrocurcumin (HHC) attenuates oxidative stress, amyloidogenesis, phosphorylated Tau (pTau) expression, neuron synaptic function, and cognitive impairment and also the potential mechanisms involved in induced permanent occlusion of bilateral common carotid arteries occlusion (BCCAO) or 2-vessel occlusion (2VO) in rats. After surgery, rats were treated with HHC (40 mg/kg) or piracetam (600 mg/kg) by oral gavage daily for 4 weeks. The results showed that HHC or piracetam attenuated oxidative stress by promoting nuclear factor erythroid 2-related factor 2 (Nrf2) activity, and alleviated expression of synaptic proteins (pre- and post-synaptic proteins) mediated by the Wingless/Integrated (Wnt)/β-catenin signaling pathway. Moreover, HHC or piracetam also improved synaptic plasticity via the brain-derived neurotrophic factor (BDNF)/Tyrosine receptor kinase B (TrkB)/cAMP responsive element binding protein (CREB) signaling pathway. In addition, HHC reduced amyloid beta (Aβ) production and pTau expression and improved memory impairment as evidenced by the Morris water maze. In conclusion, HHC exerted remarkable improvement in cognitive function in the 2VO rats possibly via the attenuation of oxidative stress, improvement in synaptic function, attenuation of amyloidogenesis, pTau, and neuronal injury, thereby improving cognitive performance.

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Data Availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

2VO:

The 2-vessel occlusion

4-HNE:

4-Hydroxynonenal

Aβ:

Amyloid-beta

AChE:

Acetylcholinesterase

AD:

Alzheimer’s disease

BCCAO:

Bilateral common carotid artery occlusion

BDNF:

Brain-derived neurotrophic factor

BuChE:

Butyrylcholinesterase

BW:

Body weight

CBF:

Cerebral blood flow

CCA:

Common carotid arteries

CCH:

Chronic cerebral hypoperfusion

CREB:

CAMP responsive element binding protein

GAP43:

Growth Associated Protein 43

GLUTs:

Glucose transporter

GSK3β:

Glycogen synthase kinase-3 beta

HHC:

Hexahydrocurcumin

HIFs:

Hypoxia-inducible factor 1

MWM:

Morris water maze test

Nrf2:

Nuclear factor erythroid 2-related factor 2

PARP1:

Poly (ADP-ribose) polymerase-1

PSD95:

Postsynaptic protein density 95

SOD:

Superoxide dismutase

SYN:

Synaptophysin

TrkB:

Tyrosine receptor kinase B

VaD:

Vascular dementia

Wnts:

Wingless/Integrated

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Funding

This work was supported by the Royal Golden Jubilee Ph.D. program (NRCT5-RGJ63004-076) and Thailand Science Research and Innovation (TSRI) (RUG6290031), Thailand. Partial support from the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research and Innovation is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Pranglada Jearjaroen, Phakkawat Thangwong, Anusorn Lungkaphin & Jiraporn Tocharus

  2. Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Chainarong Tocharus

  3. Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand

    Waraluck Chaichompoo, Jaranwit Srijun & Apichart Suksamrarn

  4. Functional Food Research Center for Well-being, Chiang Mai University, Chiang Mai, 50200, Thailand

    Jiraporn Tocharus

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  1. Pranglada Jearjaroen
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Contributions

Pranglada Jearjaroen: Conducted the experiments, performed data analysis, writing – original draft, review & editing. Phakkawat Thangwong: conducted the experiments. Chainarong Tocharus: Performed data analysis, writing – original draft, review & editing. Anusorn Lungkaphin: writing – review & editing. Waraluck Chaichompoo: Preparation of hexahydrocurcumin. Jaranwit Srijun: Preparation of hexahydrocurcumin. Apichart Suksamrarn: Preparation of hexahydrocurcumin, writing – review & editing. Jiraporn Tocharus: Conceived and designed the experiments, performed data analysis, writing – original draft, review & editing, project administration.

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Correspondence to Jiraporn Tocharus.

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Jearjaroen, P., Thangwong, P., Tocharus, C. et al. Hexahydrocurcumin Attenuates Neuronal Injury and Modulates Synaptic Plasticity in Chronic Cerebral Hypoperfusion in Rats. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03821-x

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