Gallic acid and hesperidin elevate neurotransmitters level and protect against oxidative stress, inflammation and apoptosis in aluminum chloride-induced Alzheimer's disease in rats

Ekundayo, Bidemi Emmanuel; Obafemi, Tajudeen Olabisi; Afolabi, Blessing A.; Adewale, Olusola Bolaji; Onasanya, A.; Osukoya, Olukemi Adetutu; Falode, John Adeolu; Akintayo, Christopher O.; Adu, Isaac Adekola

doi:10.1016/j.prmcm.2022.100193

Cited by 15 publications

(11 citation statements)

References 56 publications

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“…This behavioral alteration is confirmed by the biochemical changes in the AlCl 3 groups compared with the normal group. Our study findings were in agreement with the previous article stated by Ekundayo et al ( 2022 ). However, myco-fabricated ZnO-NPs treatment at two different doses significantly enhanced this diminished spatial learning and memory adjacent to the control group, and the dose of 5 mg/kg/bw was more powerful than 10 mg/kg/bw.…”

Section: Discussionsupporting

confidence: 94%

“…This reduced synthesis of dopamine and serotonin results from the availability of these precursors (Kappock et al 1996 ). The results of our investigation concurred with those of the earlier study mentioned by Ekundayo et al ( 2022 ).…”

Section: Discussionsupporting

confidence: 94%

“…This result confirms our previous study in vitro, which showed that myco-fabricated ZnO-NPs have wound healing, anti-inflammatory action (El-Sayed et al 2023a , b ). Our findings concur with earlier research that showed the ability of ZnO-NPs to reduce inflammation (Ekundayo et al 2022 ; Chen et al 2021 ; Abdulmalek et al 2021 ).…”

Section: Discussionsupporting

confidence: 93%

“…Nehru and Anand ( 2005 ) observed that decreased activities of SOD and CAT in rat’s brains exposed to AlCl 3 may be attributed to a decrease in the synthesis of enzyme proteins. Similarly, numerous studies stated that declines in activities of SOD and CAT are connected with AD (Jadhav and Kulkarni 2022 ; Ekundayo et al 2022 ; Ojha 2023 ; Chen et al 2021 ).…”

Section: Discussionmentioning

confidence: 95%

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Myco-fabricated ZnO nanoparticles ameliorate neurotoxicity in mice model of Alzheimer’s disease via acetylcholinesterase inhibition and oxidative stress reduction

et al. 2023

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Alzheimer’s disease (AD) is one of the primary health problems linked to the decrease of acetylcholine in cholinergic neurons and elevation in oxidative stress. Myco-fabrication of ZnO-NPs revealed excellent biological activities, including anti-inflammatory and acetylcholinesterase inhibitory potentials. This study aims to determine if two distinct doses of myco-fabricated ZnO-NPs have a positive impact on behavioral impairment and several biochemical markers associated with inflammation and oxidative stress in mice that have been treated by aluminum chloride (AlCl3) to induce AD. Sixty male mice were haphazardly separated into equally six groups. Group 1 was injected i.p. with 0.5 ml of deionized water daily during the experiment. Mice in group 2 received AlCl3 (50 mg/kg/day i.p.). Groups 3 and 4 were treated i.p. with 5 and 10 mg/kg/day of ZnO-NPs only, respectively. Groups 5 and 6 were given i.p. 5 and 10 mg/kg/day ZnO-NPs, respectively, add to 50 mg/kg/day AlCl3. Results showed that the AlCl3 caused an increase in the escape latency time and a reduction in the time spent in the target quadrant, indicating a decreased improvement in learning and memory. Moreover, acetylcholinesterase enzyme (AChE) activity and malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin 1β (IL-1β) levels were significantly increased, and the content of glutathione (GSH), activities of superoxide dismutase (SOD), catalase (CAT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), as well as levels of serotonin and dopamine, were decreased in brain tissues only in AlCl3 treated mice. However, treatment of mice with myco-fabrication of ZnO-NPs at doses of 5 or 10 mg/kg improves learning and memory function through ameliorate all the previous parameters in the AD mice group. The low dose of 5 mg/kg is more effective than a high dose of 10 mg/kg. In accordance with these findings, myco-fabricated ZnO-NPs could enhance memory and exhibit a protective influence against memory loss caused by AlCl3.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 95%

See 2 more Smart Citations

Myco-fabricated ZnO nanoparticles ameliorate neurotoxicity in mice model of Alzheimer’s disease via acetylcholinesterase inhibition and oxidative stress reduction

et al. 2023

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“…Y-maze test assessed working spatial and short-term memory (Ekundayo et al 2022 ) based on an animal’s natural tendency to explore new environments (Ikram et al 2019 ). The test was conducted on a wooden apparatus consisting of three similar arms (120°, 40 cm long, and 35-cm height) identified as A, B, and C. In brief, each rat was randomly put at the end of one arm and allowed to move freely in all three arms for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Mitigating effect of ferulic acid on di-(2-ethylhexyl) phthalate-induced neurocognitive dysfunction in male rats with a comprehensive in silico survey

Khalifa,

Fayed,

Ahmed

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate threatening public health-induced neurotoxicity. This neurotoxicity is associated with behavioral and biochemical deficits in male rats. Our study investigated the neuroprotective effect of ferulic acid (FA) on male rats exposed to DEHP. Thirty-two male Wistar rats were assigned to four groups. Group I control rats received corn oil, group II intoxicated rats received 300 mg/kg of DEHP, group III received 300 mg/kg of DEHP + 50 mg/kg of FA, and group IV received 50 mg/kg of FA, all agents administrated daily per os for 30 days. Anxiety-like behavior, spatial working memory, and recognition memory were assessed. Also, brain oxidative stress biomarkers, including brain malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), brain-derived neurotrophic factor (BDNF) as well as heme oxygenase-1 (HO-1) were measured. Moreover, brain histopathology examinations associated with immunohistochemistry determination of brain caspase-3 were also evaluated. Furthermore, docking simulation was adapted to understand the inhibitory role of FA on caspase-3 and NO synthase. Compared to DEHP-intoxicated rats, FA-treated rats displayed improved cognitive memory associated with a reduced anxious state. Also, the redox state was maintained with increased BNDF levels. These changes were confirmed by restoring the normal architecture of brain tissue and a decrement in the immunohistochemistry caspase-3. In conclusion, FA has potent antioxidant and antiapoptotic properties that confirm the neuroprotective activity of FA, with a possible prospect for its therapeutic capabilities and nutritional supplement value.

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Synergistic Effect of Donepezil and Neurotropic B Vitamins on Dysregulated Antioxidant, Inflammation and Neurotransmitter Status in Aluminium Chloride‐Induced Neurotoxicity in Rats

Ekundayo,

Adewale,

Obafemi

et al. 2024

Cell Biochemistry & Function

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Combination therapy offers a promising advantage because they target multiple pathways involved in the pathogenesis and progression of Alzheimer's disease. This study aimed to investigate the synergistic effect of donepezil and each of vitamin B12, vitamin B6 and vitamin B1 on aluminium chloride (AlCl3)‐induced neurotoxicity in rats. Fifty‐four rats were divided into nine groups of six. Group I received distilled water, group II—AlCl3 (100 mg/kg), group III‐ AlCl3 (100 mg/kg) + Donepezil (10 mg/kg), group IV‐AlCl3(100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B12 (5 mg/kg), group V‐AlCl3 (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B6 (5 mg/kg), group VI‐AlCl3 (100 mg/kg) + Donepezil (10 mg/kg) + Vitamin B1 (5 mg/kg), group VII‐AlCl3 (100 mg/kg) + Vitamin B12 (5 mg/kg), group VIII‐AlCl3 (100 mg/kg) + Vitamin B6 (5 mg/kg), group IX‐AlCl3 (100 mg/kg) + Vitamin B1 (5 mg/kg). Treatment lasted for 40 days. Biochemical analyses of the brain revealed that chronic administration of AlCl3 significantly increased the level of inflammatory cytokines, caspase 9, malondialdehyde, nitric oxide and acetylcholinesterase (AChE) activity, while causing a significant decrease in superoxide dismutase (SOD) activity, Nrf2, reduced glutathione, dopamine and norepinephrine. Results also showed that AlCl3 caused cognitive impairment as indicated by a reduction in the percentage alternation index and hypo‐activity towards novel object in animals treated with AlCl3 only. Moreover, results from biochemical evaluations indicated that treatment with donepezil, B vitamins and combination of donepezil and B vitamins attenuated the deficits in dopamine, norepinephrine, Nrf2, SOD and reduced glutathione, while also reducing the elevated levels of malondialdehyde, nitric oxide, AChE, caspase 9 and inflammatory markers. These observations were corroborated by result of histopathological evaluation. The combination of donepezil and vitamin B12, B6 and B1 proved to be more effective than donepezil monotherapy. Donepezil conferred significant protection against AlCl3–induced neurotoxicity, however, the combination of donepezil and vitamin B12, vitamin B6 and Vitamin B1 significantly performed better in neuroprotective indices than donepezil monotherapy. The combination of donepezil and vitamin B1 was better amongst the three combination therapies in this study.

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Gallic acid and hesperidin elevate neurotransmitters level and protect against oxidative stress, inflammation and apoptosis in aluminum chloride-induced Alzheimer's disease in rats

Cited by 15 publications

References 56 publications

Myco-fabricated ZnO nanoparticles ameliorate neurotoxicity in mice model of Alzheimer’s disease via acetylcholinesterase inhibition and oxidative stress reduction

Myco-fabricated ZnO nanoparticles ameliorate neurotoxicity in mice model of Alzheimer’s disease via acetylcholinesterase inhibition and oxidative stress reduction

Mitigating effect of ferulic acid on di-(2-ethylhexyl) phthalate-induced neurocognitive dysfunction in male rats with a comprehensive in silico survey

Synergistic Effect of Donepezil and Neurotropic B Vitamins on Dysregulated Antioxidant, Inflammation and Neurotransmitter Status in Aluminium Chloride‐Induced Neurotoxicity in Rats

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