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  1. Article ; Online: Mitragynine (Kratom)-Withdrawal behaviour and cognitive impairments can be ameliorated by an epigenetic mechanism.

    Yunusa, Suleiman / Müller, Christian P / Hassan, Zurina

    British journal of pharmacology

    2024  

    Abstract: Background and purpose: Kratom is a preparation from Mitragyna speciosa, which is used as a natural drug preparation for many purposes around the world. However, an overdose of Kratom may cause addiction-like problems including aversive withdrawal ... ...

    Abstract Background and purpose: Kratom is a preparation from Mitragyna speciosa, which is used as a natural drug preparation for many purposes around the world. However, an overdose of Kratom may cause addiction-like problems including aversive withdrawal states resulting in cognitive impairments via unknown mechanisms. Its main psychoactive alkaloid is mitragynine, showing opioid-like properties.
    Experimental approach: Here, we analysed the neuropharmacological effects of mitragynine compared with morphine withdrawal in rats and searched for a pharmacological treatment option that may reverse the occurring cognitive deficits that usually aggravate withdrawal.
    Key results: We found that withdrawal from 14-day mitragynine (1-10 mg·kg
    Conclusion and implications: The data from this work show that changes in histone expression and downstream hippocampal plasticity may explain mitragynine, but not morphine, withdrawal behaviours and cognitive impairments. Thus, it may provide a new treatment approach for aversive Kratom/mitragynine withdrawal and addiction.
    Language English
    Publishing date 2024-03-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.16352
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Mitragynine inhibits hippocampus neuroplasticity and its molecular mechanism.

    Yunusa, Suleiman / Hassan, Zurina / Müller, Christian P

    Pharmacological reports : PR

    2023  Volume 75, Issue 6, Page(s) 1488–1501

    Abstract: Background: Mitragynine (MIT), the primary indole alkaloid of kratom (Mitragyna speciosa), has been associated with addictive and cognitive decline potentials. In acute studies, MIT decreases spatial memory and inhibits hippocampal synaptic transmission ...

    Abstract Background: Mitragynine (MIT), the primary indole alkaloid of kratom (Mitragyna speciosa), has been associated with addictive and cognitive decline potentials. In acute studies, MIT decreases spatial memory and inhibits hippocampal synaptic transmission in long-term potentiation (LTP). This study investigated the impacts of 14-day MIT treatment on hippocampus synaptic transmission and its possible underlying mechanisms.
    Methods: Under urethane anesthesia, field excitatory post-synaptic potentials (fEPSP) of the hippocampal CA1 region were recorded in the Sprague Dawley (SD) rats that received MIT (1, 5, and 10 mg/kg), morphine (MOR) 5 mg/kg, or vehicle (ip). The effects of the treatments on basal synaptic transmission, paired-pulse facilitation (PPF), and LTP were assessed in the CA1 region. Analysis of the brain's protein expression linked to neuroplasticity was then performed using a western blot.
    Results: The baseline synaptic transmission's amplitude was drastically decreased by MIT at 5 and 10 mg/kg doses, although the PPF ratio before TBS remained unchanged, the PPF ratio after TBS was significantly reduced by MIT (10 mg/kg). Strong and persistent inhibition of LTP was generated in the CA1 region by MIT (5 and 10 mg/kg) doses; this effect was not seen in MIT (1 mg/kg) treated rats. In contrast to MIT (1 mg/kg), MIT (5 and 10 mg/kg) significantly raised the extracellular glutamate levels. After exposure to MIT, GluR-1 receptor expression remained unaltered. However, NMDAε2 receptor expression was markedly downregulated. The expression of pCaMKII, pERK, pCREB, BDNF, synaptophysin, PSD-95, Delta fosB, and CDK-5 was significantly downregulated in response to MIT (5 and 10 mg/kg) exposure, while MOR (5 mg/kg) significantly raised synaptophysin and Delta fosB expression.
    Conclusion: Findings from this work reveal that a smaller dose of MIT (1 mg/kg) poses no risk to hippocampal synaptic transmission. Alteration in neuroplasticity-associated proteins may be a molecular mechanism for MIT (5 and 10 mg/kg)-induced LTP disruption and cognitive impairments. Data from this work posit that MIT acted differently from MOR on neuroplasticity and its underlying mechanisms.
    MeSH term(s) Rats ; Animals ; Synaptophysin ; Rats, Sprague-Dawley ; Hippocampus ; Neuronal Plasticity ; Long-Term Potentiation ; Synaptic Transmission
    Chemical Substances mitragynine (EP479K822J) ; Synaptophysin
    Language English
    Publishing date 2023-11-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2186248-5
    ISSN 2299-5684 ; 1734-1140
    ISSN (online) 2299-5684
    ISSN 1734-1140
    DOI 10.1007/s43440-023-00541-w
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  3. Article ; Online: The dopamine D1 receptor antagonist SCH-23390 blocks the acquisition, but not expression of mitragynine-induced conditioned place preference in rats.

    Japarin, Rima Atria / Harun, Norsyifa / Hassan, Zurina / Müller, Christian P

    Behavioural brain research

    2023  Volume 453, Page(s) 114638

    Abstract: Mitragynine (MG) is the primary active constituent of Mitragyna speciosa Korth (kratom), a psychoactive Southeast Asian plant with potential therapeutic use. Numerous studies support roles of dopaminergic system in drug reward. However, the involvement ... ...

    Abstract Mitragynine (MG) is the primary active constituent of Mitragyna speciosa Korth (kratom), a psychoactive Southeast Asian plant with potential therapeutic use. Numerous studies support roles of dopaminergic system in drug reward. However, the involvement of the dopaminergic system in mediating MG reward and drug-seeking is poorly understood. Using conditioned place preference (CPP) paradigm, the present study aims to evaluate the roles of the dopamine (DA) D1 receptor in the acquisition and expression of MG-induced CPP in rats. The effects of SCH-23390, a selective DA D1 receptor antagonist, on the acquisition of MG-induced CPP were first investigated. Rats were pre-treated systemically with SCH-23390 (0, 0.1 and 0.3 mg/kg, i.p.) prior to MG (10 mg/kg) conditioning sessions. Next, we tested the effects of the DA D1 receptor antagonist on the expression of MG-induced CPP. Furthermore, the effects of a MG-priming dose (5 mg/kg) on the reinstatement of extinguished CPP were tested. The results showed that SCH-23390 dose-dependently suppressed the acquisition of a MG-induced CPP. In contrast, SCH-23390 had no effect on the expression of a MG-induced CPP. The findings of this study suggested a crucial role of the DA D1 receptor in the acquisition, but not the expression of the rewarding effects of MG in a CPP test. Furthermore, blockade of the D1-like receptor during conditioning did not prevent MG priming effects on CPP reinstatement test, suggesting no role for the DA D1 receptor in reinstatement sensitivity.
    MeSH term(s) Animals ; Rats ; Benzazepines/pharmacology ; Dopamine ; Dopamine Antagonists/pharmacology ; Receptors, Dopamine D1
    Chemical Substances Benzazepines ; Dopamine (VTD58H1Z2X) ; Dopamine Antagonists ; mitragynine (EP479K822J) ; Receptors, Dopamine D1 ; SCH 23390
    Language English
    Publishing date 2023-08-22
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2023.114638
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  4. Article ; Online: Morris water maze: a versatile and pertinent tool for assessing spatial learning and memory.

    Othman, Muhammad Zulfadhli / Hassan, Zurina / Che Has, Ahmad Tarmizi

    Experimental animals

    2022  Volume 71, Issue 3, Page(s) 264–280

    Abstract: Since its development about 40 years ago (1981-2021), Morris water maze has turned into a very popular tool for assessing spatial learning and memory. Its many advantages have ensured its pertinence to date. These include its effectiveness in evaluating ... ...

    Abstract Since its development about 40 years ago (1981-2021), Morris water maze has turned into a very popular tool for assessing spatial learning and memory. Its many advantages have ensured its pertinence to date. These include its effectiveness in evaluating hippocampal-dependent learning and memory, exemption from motivational differences across diverse experimental manipulations, reliability in various cross-species studies, and adaptability to many experimental conditions with various test protocols. Nonetheless, throughout its establishment, several experimental and analysis loopholes have galvanized researchers to assess ways in which it could be improved and adapted to fill this gap. Therefore, in this review, we briefly summarize these developments since the early years of its establishment through to the most recent advancements in computerized analysis, offering more comprehensive analysis paradigms. In addition, we discuss the adaptability of the Morris water maze across different test versions and analysis paradigms, providing suggestions with regard to the best paradigms for particular experimental conditions. Hence, the proper selection of the experimental protocols, analysis paradigms, and consideration of the assay's limitations should be carefully considered. Given that appropriate measures are taken, with various adaptations made, the Morris water maze will likely remain a relevant tool to assess the mechanisms of spatial learning and memory.
    MeSH term(s) Animals ; Maze Learning ; Memory ; Morris Water Maze Test ; Reproducibility of Results ; Spatial Learning
    Language English
    Publishing date 2022-03-18
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 2088228-2
    ISSN 1881-7122 ; 1341-1357 ; 0007-5124
    ISSN (online) 1881-7122
    ISSN 1341-1357 ; 0007-5124
    DOI 10.1538/expanim.21-0120
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  5. Article ; Online: Mitragynine, a primary constituent of kratom reinstates morphine-seeking behaviour in rats.

    Japarin, Rima Atria / Harun, Norsyifa / Hassan, Zurina / Shoaib, Mohammed

    Behavioural pharmacology

    2022  Volume 34, Issue 2-3, Page(s) 123–130

    Abstract: Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to ... ...

    Abstract Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.
    MeSH term(s) Rats ; Animals ; Morphine/pharmacology ; Analgesics, Opioid/pharmacology ; Rats, Sprague-Dawley ; Mitragyna ; Secologanin Tryptamine Alkaloids/pharmacology ; Opioid-Related Disorders/drug therapy ; Extinction, Psychological
    Chemical Substances Morphine (76I7G6D29C) ; Analgesics, Opioid ; mitragynine (EP479K822J) ; Secologanin Tryptamine Alkaloids
    Language English
    Publishing date 2022-12-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1027374-8
    ISSN 1473-5849 ; 0955-8810
    ISSN (online) 1473-5849
    ISSN 0955-8810
    DOI 10.1097/FBP.0000000000000715
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  6. Article ; Online: Mini review: Potential therapeutic values of mitragynine as an opioid substitution therapy.

    Harun, Norsyifa / Kamaruzaman, Nur Azzalia / Mohamed Sofian, Zarif / Hassan, Zurina

    Neuroscience letters

    2022  Volume 773, Page(s) 136500

    Abstract: Opioid use disorder (OUD) has become a significant public health issue worldwide. Methadone and buprenorphine are the most common medications used for treating OUD. These drugs have the potential to assist many patients in managing their opioid ... ...

    Abstract Opioid use disorder (OUD) has become a significant public health issue worldwide. Methadone and buprenorphine are the most common medications used for treating OUD. These drugs have the potential to assist many patients in managing their opioid dependence and withdrawal but they are currently misused and associated with certain compliance issues, side effects, and risk of relapse. As an opioid-like herbal supplement, Mitragyna speciosa Korth or kratom has received increased attention for managing chronic pain and opioid withdrawal symptoms. Nevertheless, the use of kratom as a self-treatment medication for opioid dependence continues to be controversial due to concerns raised about its effectiveness, safety, and abuse liability. The main active alkaloid constituent of the plant, mitragynine, has been shown to act as a partial mu-opioid agonist. Given this pharmacology, studies have been focusing on this psychoactive compound to examine its potential therapeutic values as medication-assisted therapy (MAT). This review aims to provide a current preclinical overview of mitragynine as a prospective novel option for MAT and summarise the recent developments in determining if the plant's active alkaloid could provide an alternative to opioids in the treatment of OUD.
    MeSH term(s) Analgesics, Opioid/adverse effects ; Humans ; Mitragyna/adverse effects ; Opiate Substitution Treatment ; Opioid-Related Disorders/drug therapy ; Prospective Studies ; Secologanin Tryptamine Alkaloids/pharmacology ; Secologanin Tryptamine Alkaloids/therapeutic use ; Substance Withdrawal Syndrome/drug therapy
    Chemical Substances Analgesics, Opioid ; Secologanin Tryptamine Alkaloids ; mitragynine (EP479K822J)
    Language English
    Publishing date 2022-01-31
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 194929-9
    ISSN 1872-7972 ; 0304-3940
    ISSN (online) 1872-7972
    ISSN 0304-3940
    DOI 10.1016/j.neulet.2022.136500
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  7. Article ; Online: The Emerging Roles of π Subunit-Containing GABA

    Juvale, Iman Imtiyaz Ahmed / Hassan, Zurina / Has, Ahmad Tarmizi Che

    International journal of medical sciences

    2021  Volume 18, Issue 16, Page(s) 3851–3860

    Abstract: Cancer is one of the leading causes of death in both developed and developing countries. Due to its heterogenous nature, it occurs in various regions of the body and often goes undetected until later stages of disease progression. Feasible treatment ... ...

    Abstract Cancer is one of the leading causes of death in both developed and developing countries. Due to its heterogenous nature, it occurs in various regions of the body and often goes undetected until later stages of disease progression. Feasible treatment options are limited because of the invasive nature of cancer and often result in detrimental side-effects and poor survival rates. Therefore, recent studies have attempted to identify aberrant expression levels of previously undiscovered proteins in cancer, with the hope of developing better diagnostic tools and pharmaceutical options. One class of such targets is the π-subunit-containing γ-aminobutyric acid type A receptors. Although these receptors were discovered more than 20 years ago, there is limited information available. They possess atypical functional properties and are expressed in several non-neuronal tissues. Prior studies have highlighted the role of these receptors in the female reproductive system. New research focusing on the higher expression levels of these receptors in ovarian, breast, gastric, cervical, and pancreatic cancers, their physiological function in healthy individuals, and their pro-tumorigenic effects in these cancer types is reviewed here.
    MeSH term(s) Animals ; Female ; Humans ; Neoplasms/classification ; Neoplasms/epidemiology ; Neoplasms/genetics ; Neoplasms/pathology ; Receptors, GABA-A/physiology ; gamma-Aminobutyric Acid/metabolism
    Chemical Substances GABRP protein, human ; Receptors, GABA-A ; gamma-Aminobutyric Acid (56-12-2)
    Language English
    Publishing date 2021-10-31
    Publishing country Australia
    Document type Journal Article ; Review
    ZDB-ID 2151424-0
    ISSN 1449-1907 ; 1449-1907
    ISSN (online) 1449-1907
    ISSN 1449-1907
    DOI 10.7150/ijms.60928
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  8. Article ; Online: TRPM4 blocking antibody reduces neuronal excitotoxicity by specifically inhibiting glutamate-induced calcium influx under chronic hypoxia.

    Poore, Charlene P / Hazalin, Nurul A M N / Wei, Shunhui / Low, See Wee / Chen, Bo / Nilius, Bernd / Hassan, Zurina / Liao, Ping

    Neurobiology of disease

    2024  Volume 191, Page(s) 106408

    Abstract: Excitotoxicity arises from unusually excessive activation of excitatory amino acid receptors such as glutamate receptors. Following an energy crisis, excitotoxicity is a major cause for neuronal death in neurological disorders. Many glutamate antagonists ...

    Abstract Excitotoxicity arises from unusually excessive activation of excitatory amino acid receptors such as glutamate receptors. Following an energy crisis, excitotoxicity is a major cause for neuronal death in neurological disorders. Many glutamate antagonists have been examined for their efficacy in mitigating excitotoxicity, but failed to generate beneficial outcome due to their side effects on healthy neurons where glutamate receptors are also blocked. In this study, we found that during chronic hypoxia there is upregulation and activation of a nonselective cation channel TRPM4 that contributes to the depolarized neuronal membrane potential and enhanced glutamate-induced calcium entry. TRPM4 is involved in modulating neuronal membrane excitability and calcium signaling, with a complex and multifaceted role in the brain. Here, we inhibited TRPM4 using a newly developed blocking antibody M4P, which could repolarize the resting membrane potential and ameliorate calcium influx upon glutamate stimulation. Importantly, M4P did not affect the functions of healthy neurons as the activity of TRPM4 channel is not upregulated under normoxia. Using a rat model of chronic hypoxia with both common carotid arteries occluded, we found that M4P treatment could reduce apoptosis in the neurons within the hippocampus, attenuate long-term potentiation impairment and improve the functions of learning and memory in this rat model. With specificity to hypoxic neurons, TRPM4 blocking antibody can be a novel way of controlling excitotoxicity with minimal side effects that are common among direct blockers of glutamate receptors.
    MeSH term(s) Rats ; Animals ; Glutamic Acid/metabolism ; Calcium/metabolism ; Receptors, Glutamate/metabolism ; Neurons/metabolism ; Hypoxia/metabolism ; TRPM Cation Channels/metabolism
    Chemical Substances Glutamic Acid (3KX376GY7L) ; Calcium (SY7Q814VUP) ; Receptors, Glutamate ; TRPM4 protein, rat ; TRPM Cation Channels
    Language English
    Publishing date 2024-01-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1211786-9
    ISSN 1095-953X ; 0969-9961
    ISSN (online) 1095-953X
    ISSN 0969-9961
    DOI 10.1016/j.nbd.2024.106408
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  9. Article ; Online: Centella asiatica (L.) Urban. Attenuates Cell Damage in Hydrogen Peroxide-Induced Oxidative Stress in Transgenic Murine Embryonic Stem Cell Line-Derived Neural-Like Cells: A Preliminary Study for Potential Treatment of Alzheimer's Disease.

    Mansor, Nur Izzati / Ling, King-Hwa / Rosli, Rozita / Hassan, Zurina / Adenan, Mohd Ilham / Nordin, Norshariza

    Journal of Alzheimer's disease : JAD

    2023  Volume 94, Issue s1, Page(s) S21–S44

    Abstract: Background: Centella asiatica (L.) (C. asiatica) is commonly known in South East and South East Asia communities for its nutritional and medicinal benefits. Besides being traditionally used to enhance memory and accelerate wound healing, its ... ...

    Abstract Background: Centella asiatica (L.) (C. asiatica) is commonly known in South East and South East Asia communities for its nutritional and medicinal benefits. Besides being traditionally used to enhance memory and accelerate wound healing, its phytochemicals have been extensively documented for their neuroprotective, neuroregenerative, and antioxidant properties.
    Objective: The present study aims to investigate the effects of a standardized raw extract of C. asiatica (RECA) on hydrogen peroxide (H2O2)-induced oxidative stress and apoptotic death in neural-like cells derived from mouse embryonic stem (ES) cell line.
    Methods: A transgenic mouse ES cell (46C) was differentiated into neural-like cells using 4-/4+ protocol with addition of all-trans retinoic acid. These cells were then exposed to H2O2 for 24 h. The effects of RECA on H2O2-induced neural-like cells were assessed through cell viability, apoptosis, and reactive oxygen species (ROS) assays, as well as neurite length measurement. The gene expression levels of neuronal-specific and antioxidant markers were assessed by RT-qPCR analysis.
    Results: Pre-treatment with H2O2 for 24 hours, in a dose-dependent manner, damaged neural-like cells as marked by a decrease in cell viability, substantial increase in intracellular ROS accumulation, and increase in apoptotic rate compared to untreated cells. These cells were used to treat with RECA. Treatment with RECA for 48 h remarkably restored cell survival and promoted neurite outgrowth in the H2O2- damaged neurons by increasing cell viability and decreasing ROS activity. RT-qPCR analysis revealed that RECA upregulated the level of antioxidant genes such as thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1) of treated cells, as well as the expression level of neuronal-specific markers such as Tuj1 and MAP2 genes, suggesting their contribution in neuritogenic effect.
    Conclusion: Our findings indicate that RECA promotes neuroregenerative effects and exhibits antioxidant properties, suggesting a valuable synergistic activity of its phytochemical constituents, thus, making the extract a promising candidate in preventing or treating oxidative stress-associated Alzheimer's disease.
    MeSH term(s) Animals ; Mice ; Hydrogen Peroxide/toxicity ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Reactive Oxygen Species/metabolism ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Centella/chemistry ; Centella/metabolism ; Oxidative Stress ; Apoptosis ; Animals, Genetically Modified ; Cell Line ; Cell Survival ; Embryonic Stem Cells
    Chemical Substances Hydrogen Peroxide (BBX060AN9V) ; Antioxidants ; Reactive Oxygen Species
    Language English
    Publishing date 2023-06-19
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-221233
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  10. Article ; Online: Effects of clitorienolactones from Clitoria ternatea root on calcium channel mediating hippocampal long-term potentiation in rats induced chronic cerebral hypoperfusion.

    Ahad, Mohamad Anuar / Chear, Nelson Jeng-Yeou / Abdullah, Muhammad Hazim / Ching-Ga, Tan Ai Fein / Liao, Ping / Wei, Shunhui / Murugaiyah, Vikneswaran / Hassan, Zurina

    Ageing research reviews

    2024  Volume 96, Page(s) 102252

    Abstract: Chronic cerebral hypoperfusion (CCH) is a common mechanism of acute brain injury due to impairment of blood flow to the brain. Moreover, a prolonged lack of oxygen supply may result in cerebral infarction or global ischemia, which subsequently causes ... ...

    Abstract Chronic cerebral hypoperfusion (CCH) is a common mechanism of acute brain injury due to impairment of blood flow to the brain. Moreover, a prolonged lack of oxygen supply may result in cerebral infarction or global ischemia, which subsequently causes long-term memory impairment. Research on using Clitoria ternatea root extract for treating long-term memory has been studied extensively. However, the bioactive compound contributing to its neuroprotective effects remains uncertain. In the present study, we investigate the effects of clitorienolactone A (CLA) and B (CLB) from the roots of Clitoria ternatea extract on hippocampal neuroplasticity in rats induced by CCH. CLA and CLB were obtained using column chromatography. The rat model of CCH was induced using two-vessel occlusion surgery (2VO). The 2VO rats were given 10 mg/kg of CLA and CLB orally, followed by hippocampal neuroplasticity recording using in vivo electrophysiological. Rats received CLA and CLB (10 mg/kg) significantly reversed the impairment of long-term potentiation following 2VO surgery. Furthermore, we investigate the effect of CLA and CLB on the calcium channel using the calcium imaging technique. During hypoxia, CLA and CLB sustain the increase in intracellular calcium levels. We next predict the binding interactions of CLA and CLB against NMDA receptors containing GluN2A and GluN2B subunits using in silico molecular docking. Our result found that both CLA and CLB exhibited lower binding affinity against GluN2A and GluN2B subunits. Our findings demonstrated that bioactive compounds from Clitoria ternatea improved long-term memory deficits in the chronic cerebral hypoperfusion rat model via calcium uptake. Hence, CLA and CLB could be potential therapeutic tools for treating cognitive dysfunction.
    MeSH term(s) Rats ; Humans ; Animals ; Clitoria/chemistry ; Calcium Channels/pharmacology ; Calcium Channels/therapeutic use ; Long-Term Potentiation ; Calcium ; Molecular Docking Simulation ; Brain Ischemia/drug therapy ; Hippocampus ; Maze Learning/physiology
    Chemical Substances Calcium Channels ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2024-03-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2075672-0
    ISSN 1872-9649 ; 1568-1637
    ISSN (online) 1872-9649
    ISSN 1568-1637
    DOI 10.1016/j.arr.2024.102252
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