6-Methoxyflavone and Donepezil Behavioral Plus Neurochemical Correlates in Reversing Chronic Ethanol and Withdrawal Induced Cognitive Impairment

Arif, Mehreen; Rauf, Khalid; Rehman, Naeem Ur; Tokhi, Ahmed; Ikram, Muhammad; Sewell, Robert David Edmund

doi:10.2147/dddt.s360677

Cited by 7 publications

(7 citation statements)

References 98 publications

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“…The number of line crossings was noted by an observer who was blinded to the treatments, and data was analysed accordingly. 18 , 19 …”

Section: Methodsmentioning

confidence: 99%

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a Murine Model of Depression, Anxiety and Cognition

Gohar,

Ali,

Rashid

et al. 2023

DDDT

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Background and Objective Gabapentin is a commonly prescribed antiepileptic agent for seizures, which is also used for pain and addiction management. Due to growing evidence of its abuse liability, there has been an incentive to synthesise potentially useful gabapentin derivatives devoid of adverse effects. A gabapentin adduct with a fluoxetine moiety, GBP1F, was assessed for any sedative, cognitive, anxiolytic, or antidepressant-like actions in murine behavioral models. Materials and Methods Selected groups of mice were used for each behavioral paradigm, and the effect of GBP1F (5, 10, and 15 mg/kg) was assessed using spontaneous locomotor activity, the tail suspension test, elevated plus maze test, and the Y maze test models. Immediately following behavioral experiments, postmortem striatal and hippocampal tissues were evaluated for the effect of GBP1F on concentrations of dopamine, DOPAC, HVA, serotonin, 5-HIAA, vitamin C, and noradrenaline using high performance liquid chromatography with electrochemical detection. Results GBP1F induced a mild suppression of locomotor activity, ameliorated anxiety and depression-like behavior, did not alter cognitive behavior, and raised serotonin and 5-HIAA concentrations in the hippocampus and striatum. GBP1F also positively enhanced dopamine and vitamin C tissue levels in the striatum. Thus, GBP1F represents a compound with anxiolytic- and antidepressant-like effects though further studies are warranted at the molecular level to focus on the precise mechanism(s) of action.

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“…The number of line crossings was noted by an observer who was blinded to the treatments, and data was analysed accordingly. 18 , 19 …”

Section: Methodsmentioning

confidence: 99%

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a Murine Model of Depression, Anxiety and Cognition

Gohar,

Ali,

Rashid

et al. 2023

DDDT

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“…Homogenization of the tissues was carried out in chilled perchloric acid (0.2%) following cold centrifugation (4°C; 12,000 rpm) and the supernatant was then separated. Once the samples were prepared, they were passed through a 0.45 mm filter and then analyzed using HPLC ( Ur Rehman et al, 2020 ; Arif et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…For vitamin C, dopamine and noradrenaline analysis, methanol, HPLC grade water and 20 mM monobasic sodium phosphate (5:95, v/v) were used with isocratic elution at 280 nm at a column temperature of 35°C and an elution rate of 0.5 mL/min. For the analysis of adenosine, inosine and hypoxanthine, acetonitrile, HPLC grade water and 0.01 M monobasic sodium phosphate (5:95 v/v) was used with isocratic elution at 260 nm, with the column at room temperature and a flow rate of 1.0 mL/min ( Ur Rehman et al, 2020 ; Arif et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

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5,7-Dimethoxycoumarin ameliorates vincristine induced neuropathic pain: potential role of 5HT3 receptors and monoamines

Usman,

Malik,

Tokhi

et al. 2023

Front. Pharmacol.

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Vincristine is the drug of choice for Hodgkin’s lymphoma, acute lymphoblastic leukemia, and non-Hodgkin lymphoma. Despite its significant anticancer effects, it causes dose-dependent neuropathy, leading to compulsive dose reduction. The available drugs used for vincristine-induced neuropathic pain (VINP) have a range of safety, efficacy, and tolerability issues prompting a search for new therapies. 5,7-Dimethoxycoumarin (5,7-DMC) also known as citropten, is a natural coumarin found in the essential oils of citrus plants such as lime, lemons, and bergamots, and it possesses both antidepressant and anti-inflammatory effects. This study was designed to investigate the possible analgesic and antiallodynic effects of 5,7-DMC in a murine model of VINP. Vincristine was administered to groups of BALB/c male mice (0.1 mg/kg intraperitoneally) once daily for 14 days to induce VINP. Thermal hyperalgesia and mechanical allodynia were quantified using the tail immersion test and von Frey filament application method. The levels of monoamine neurotransmitters and vitamin C in frontal cortical, striatal and hippocampal tissues, as well as the TNF-α level in plasma, were quantified using high performance liquid chromatography and ELISA respectively. On day 15 of the protocol, acute treatment with 5,7-DMC clearly reversed VINP thermal hyperalgesia, mechanical static allodynia, mechanical dynamic allodynia, and cold allodynia. The activity of 5,7-DMC against hyperalgesia and allodynia was inhibited by pretreatment with ondansetron but not naloxone, implicating a 5-HT3 receptor involvement. VINP vitamin C levels were restored by 5,7-DMC in the frontal cortex, and changes in serotonin, dopamine, adenosine, inosine and hypoxanthine levels caused by vincristine were reversed either fully or partially. Additionally, the vincristine-induced rise in hippocampal serotonin, dopamine, inosine and striatal serotonin was appreciably reversed by 5,7-DMC. 5,7-DMC also reversed the vincristine-induced increase in the plasma level of TNF-α. In negating the changes in the levels of some neurotransmitters in the brain caused by vincristine, 5,7-DMC showed stronger effects than gabapentin. It was concluded that, there is a potential role of 5-HT3 receptors and monoamines in the amelioration of VINP induced by 5,7-DMC, and the use of this compound warrants further investigation.

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“…When an animal’s head was facing the object, or when the distance between its head and the object was 1 cm or less, or when the animal was sniffing or touching the object, it was regarded to be exploration time ( Garofalo et al, 2023 ). Between each experiment, 70% ethanol was used to clean the items and the box ( Arif et al, 2022 ). A recognition index (RI) and a discrimination index (DI) were derived from the data ( Hendrickx et al, 2022 ) as follows:

…”

Section: Methodsmentioning

confidence: 99%

Diosgenin normalization of disrupted behavioral and central neurochemical activity after single prolonged stress

Malik,

Usman,

Arif

et al. 2023

Front. Pharmacol.

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Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice.Methodology: SPS was induced by restraining animals for 2 h, followed by 20 min of forced swim, recuperation for 15 min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60 mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels.Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice.Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD.

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6-Methoxyflavone and Donepezil Behavioral Plus Neurochemical Correlates in Reversing Chronic Ethanol and Withdrawal Induced Cognitive Impairment

Cited by 7 publications

References 98 publications

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a Murine Model of Depression, Anxiety and Cognition

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a Murine Model of Depression, Anxiety and Cognition

5,7-Dimethoxycoumarin ameliorates vincristine induced neuropathic pain: potential role of 5HT3 receptors and monoamines

Diosgenin normalization of disrupted behavioral and central neurochemical activity after single prolonged stress

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