Research article Topical Sections

Naringin ameliorates motor dysfunction and exerts neuroprotective role against vanadium-induced neurotoxicity

  • Exposure to vanadium has been known to lead to a progressive neurodegenerative disorder like Parkinson's disease. Naringin is a known flavonoid glycoside that is mostly seen in the flesh of grapefruit and orange and is believed to have protective effects for the treatment of neurodegenerative disorders. This study sought to investigate the role of Naringin in the treatment of vanadium-induced neurotoxicity. Vanadium (10 mg/kg BW) was injected intraperitoneally to induce motor dysfunction, followed by treatment with Naringin (30 mg/kg BW) intraperitoneally for 14 days. Oxidative stress imbalance was monitored by checking Glutathione Peroxidase (GPX) and Catalase levels. Histological and immunohistochemical alterations were observed using RBFOX3 polyclonal antibody to determine neuronal cell distribution and NLRP3 inflammasome antibody as a marker of inflammation. Exposure to vanadium induces neurotoxicity by significantly increasing the Catalase and Glutathione Peroxidase (GPX) levels. Vanadium administration also led to increased inflammatory cells and a significant reduction of the viable neuronal cells in the SNc and CPu. Treatment with Naringin showed a neuroprotective role by dependently restoring the Catalase and Glutathione Peroxidase (GPX) levels, inflammasome activation, and neuronal damage in the SNc and CPu. Naringin demonstrated anti-oxidative, and anti-inflammatory responses by inhibiting oxidative stress, and inflammation and exerts neuroprotective effects by inhibiting apoptosis following vanadium-induced neurotoxicity in adult Wistar rats.

    Citation: Adeshina O. Adekeye, Adedamola A. Fafure, Ayoola E. Ogunsemowo, Linus A. Enye, Olusola S. Saka, Oluwatosin O. Ogedengbe. Naringin ameliorates motor dysfunction and exerts neuroprotective role against vanadium-induced neurotoxicity[J]. AIMS Neuroscience, 2022, 9(4): 536-550. doi: 10.3934/Neuroscience.2022031

    Related Papers:

    [1] Zohaer Muttalib, Dana Aboukhalil, Chisom Nwosu, Dave D. Manguerra, Jimmy Wen, Ubaid Ansari, Meraj Alam, Ihab Abed, Ethan Tabaie, Ahmed Salem, Forshing Lui . Gluten and its relationship with inflammation and Parkinson's Disease: A literature review. AIMS Neuroscience, 2025, 12(1): 28-41. doi: 10.3934/Neuroscience.2025004
    [2] Ubaid Ansari, Alexi Omid, Dawnica Nadora, Jimmy Wen, Arman Omid, Forshing Lui . Outcomes of dietary interventions in the prevention and progression of Parkinson's disease: A literature review. AIMS Neuroscience, 2024, 11(4): 520-532. doi: 10.3934/Neuroscience.2024032
    [3] Amber Woodard, Brandon Barbery, Reid Wilkinson, Jonathan Strozyk, Mathew Milner, Patrick Doucette, Jarred Doran, Kendra Appleby, Henry Atwill, Wade E. Bell, James E. Turner . The role of neuronal nitric oxide and its pathways in the protection and recovery from neurotoxin-induced de novo hypokinetic motor behaviors in the embryonic zebrafish (Danio rerio). AIMS Neuroscience, 2019, 6(1): 25-42. doi: 10.3934/Neuroscience.2019.1.25
    [4] Adeshina O. Adekeye, Adedamola A. Fafure, Morayo M. Omodele, Lawrence D. Adedayo, Victor O. Ekundina, Damilare A. Adekomi, Ephraim Samuel Jen, Thomas K. Adenowo . Flavonoid glycoside fraction of Ginkgo biloba extract modulates antioxidants imbalance in vanadium-induced brain damage. AIMS Neuroscience, 2023, 10(2): 178-189. doi: 10.3934/Neuroscience.2023015
    [5] Sairam Ramesh, Arosh S. Perera Molligoda Arachchige . Depletion of dopamine in Parkinson's disease and relevant therapeutic options: A review of the literature. AIMS Neuroscience, 2023, 10(3): 200-231. doi: 10.3934/Neuroscience.2023017
    [6] Ubaid Ansari, Jimmy Wen, Burhaan Syed, Dawnica Nadora, Romteen Sedighi, Denise Nadora, Vincent Chen, Forshing Lui . Analyzing the potential of neuronal pentraxin 2 as a biomarker in neurological disorders: A literature review. AIMS Neuroscience, 2024, 11(4): 505-519. doi: 10.3934/Neuroscience.2024031
    [7] Marios G. Krokidis . Identification of biomarkers associated with Parkinson’s disease by gene expression profiling studies and bioinformatics analysis. AIMS Neuroscience, 2019, 6(4): 333-345. doi: 10.3934/Neuroscience.2019.4.333
    [8] Anmol Kumar, Ajay Kumar Gupta, Prashant Kumar Singh . Novel perspective of therapeutic modules to overcome motor and nonmotor symptoms in Parkinson's disease. AIMS Neuroscience, 2024, 11(3): 312-340. doi: 10.3934/Neuroscience.2024020
    [9] mgr Natalia Białoń, dr hab. n. o zdr. Dariusz Górka, mgr Mikołaj Górka . The brain-gut axis: communication mechanisms and the role of the microbiome as a neuroprotective factor in the development of neurodegenerative diseases: A literature overview. AIMS Neuroscience, 2024, 11(3): 289-311. doi: 10.3934/Neuroscience.2024019
    [10] Manami Inagaki, Masayuki Somei, Tatsunori Oguchi, Ran Ono, Sachie Fukutaka, Ikumi Matsuoka, Mayumi Tsuji, Katsuji Oguchi . Neuroprotective Effects of Dexmedetomidine against Thapsigargin-induced ER-stress via Activity of α2-adrenoceptors and Imidazoline Receptors. AIMS Neuroscience, 2016, 3(2): 237-252. doi: 10.3934/Neuroscience.2016.2.237
  • Exposure to vanadium has been known to lead to a progressive neurodegenerative disorder like Parkinson's disease. Naringin is a known flavonoid glycoside that is mostly seen in the flesh of grapefruit and orange and is believed to have protective effects for the treatment of neurodegenerative disorders. This study sought to investigate the role of Naringin in the treatment of vanadium-induced neurotoxicity. Vanadium (10 mg/kg BW) was injected intraperitoneally to induce motor dysfunction, followed by treatment with Naringin (30 mg/kg BW) intraperitoneally for 14 days. Oxidative stress imbalance was monitored by checking Glutathione Peroxidase (GPX) and Catalase levels. Histological and immunohistochemical alterations were observed using RBFOX3 polyclonal antibody to determine neuronal cell distribution and NLRP3 inflammasome antibody as a marker of inflammation. Exposure to vanadium induces neurotoxicity by significantly increasing the Catalase and Glutathione Peroxidase (GPX) levels. Vanadium administration also led to increased inflammatory cells and a significant reduction of the viable neuronal cells in the SNc and CPu. Treatment with Naringin showed a neuroprotective role by dependently restoring the Catalase and Glutathione Peroxidase (GPX) levels, inflammasome activation, and neuronal damage in the SNc and CPu. Naringin demonstrated anti-oxidative, and anti-inflammatory responses by inhibiting oxidative stress, and inflammation and exerts neuroprotective effects by inhibiting apoptosis following vanadium-induced neurotoxicity in adult Wistar rats.


    Abbreviations

    GPX:

    Glutathione Peroxidase; 

    ER:

    Endoplasmic Reticulum; 

    VAN:

    Vanadium; 

    NAR:

    Naringin; 

    SNc:

    Substantia nigra pars compacta; 

    CPu:

    Caudate putamen; 

    GDNF:

    Glial cell line-derived neurotrophic factor; 

    TNF:

    Tumour Necrosis Factor

    Vanadium is a trace element that has a function in living organisms most especially plants and animals, by acting as a growth promoting factor in young animals and stimulating chlorophyll synthesis in plants [1]. The role of vanadium in biological systems depends on the biophysical state especially the valence state and solubility, the dose, route and duration of exposure [2]. Vanadium can be released into the atmosphere at high amounts through man made sources like burning of fossil fuels, spillage of heavy oils especially in places like Niger delta Nigeria, one of the largest petroleum rich region in Africa [3]. One of the major public health hazards that has been associated with neurological and oxidative damage is dietary and occupational exposure of vanadium [6]. The dietary exposure of vanadium can be as a result of consuming infected food and water, while occupational exposure can be through air, or typical factory system. It has been reported that vanadium is needed in lower dose in the body for normal bone growth, and it may significantly lower blood sugar levels in patient with type 2 diabetes, it has been used as a treatment of heart disease, tuberculosis, cancer, syphilis, and has been reported to improved athletic performance in weight training. However, exposure to higher dose of vanadium due to increasing mining, smelting, weathering of rocks, sediments rich in vanadium, and infected food may pose a major health concern [2]. This higher concentration might enter the body system through the lungs and stomach, where it's been taking-up via the blood stream and been deposited in the brain. Its accumulation in the brain might induces oxidative stress and has a result, promote apoptotic cell death in the substantia nigral dopaminergic neurons, which leads to early pathogenesis of Parkinson's disease [1]. Naringin (NAR) is a well-known flavanone glycoside of tropical and subtropical fruits. It has different biological and pharmacological influence such as anti-inflammatory, antioxidant and lipid-lowering activities. It is also known to possess neuroprotective effect against neurodegenerative disorders through modulating the oxidative stress and inflammatory responses [4],[5]. Studies on NAR against neurodegenerative disease showed its anti-apoptoticproperty by inducing the glucose regulated protein 78 (GRP78), the endoplasmic reticulum (ER) chaperone and anti-inflammatory property by reducing the inflammatory cytokines and free radicals. All these findings pointed out that NAR can be considered as potential neuroprotective agent through its antioxidant activity [6]. This study aim to determine anti-inflammatory and anit-oxidative response of Naringin, the neuronal cells distribution pattern in the Substantia nigra (SNc) and Caudate Putamen (CPu) following vanadium induced neurotoxicity.

    A total of 40 healthy male Wistar rats (age: 18 weeks, weight: 150–170 g), gotten from animal holdings of the Department of Anatomy, Afe Babalola University, Ado-Ekiti, were used for this research. They were placed in a standard laboratory rat cage under normal light and dark circle with access to pellet-fed with water ad libitum. All procedures were precisely in agreement with the guidance in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and the Department of Human Anatomy, College of Medical and Health Sciences, Afe Babalola University Ado Ekiti, Nigeria (AB/EC/22/01/98).

    The rats were randomly divided into four groups (n = 10). Group A (Control: normal saline), Group B (Naringin at 30 mg/kg BW intraperitoneally), Group C (Naringin at 30 mg/kg BW and Vanadium at 10mg/kg BW), Group D (Vanadium at 10mg/kg BW intraperitoneally). The duration of the experiment was 14 days [7],[8].

    RBFOX3 and NLRP3 polyclonal antibody (Elabscience), 2-step plus poly-HRP anti-mouse/rabbit IgG Detection system (Elabscience), DAB solution, Triton-X, phosphate buffered formal saline (Elabscience), Hematoxylin and eosin (Bisolab), Ethanol and Xylene (Bisolab).

    After the last administration, the animals were anesthetized by intraperitoneal injection of 10 mg/kg BW ketamine hydrochloride. The animals were sacrificed through intra-cardiac perfusion fixation. The brain was removed, and fixed inside 4% paraformaldehyde, the region of Substantia nigra and caudate putamen was grossed and post-fixed, and stored at room temperature until needed for histological and immunohistochemical analysis. The brain sections for biochemical analysis was homogenized and centrifuged at 10,000 rpm for 10 min at 4 °C. The supernatant were isolated and used to access Glutathione Peroxidase and Catalase activities.

    The experimental animals were sacrificed 24 hours after the last administration under ketamine anesthesia. For immunohistochemistry studies sections of the caudate putamen and the substantia nigra (Section: 5 µm thick) were coronally section with a rotary microtome. Endogenous peroxidase activity within the tissue sections were briefly removed by incubating the sections in 3% H2O2 for 10 min at 37 °C after regular dewaxing and dehydration. According to the Elabscience protocol, sections were immune-stained with primary antibodies directed againstneuronal cells (RBFOX3 polyclonal antibodies) to determine neuronal cell distribution, and inflammation (NLRP3 polyclonal antibodies) to mark for inflammatory cells (NLRP3 1:200; RBFOX3 1:150, Elabscience, china).

    An OPTO-Edu industrial camera light microscope connected to a computer with an image-processing and analysis software Image-J (Version 1.53) were used to analyze the photomicrograph. The image were enhanced using oil immersion and the system was adjusted to obtain clarity and resolution. In a given square area, the total positive cells was counted and calculated. 30 sections (5 µm) of the SNc and CPu in each animal were analysed. With the aid of the software mentioned above, a non-destructive grid of lines was set to guide against counting the same cells twice.

    Differences among multiple groups were statistically analyzed using One-way ANOVA and post hoc Turkey test. Graph Pad Prism 5 (Version 5.03, Graphpad Inc.) was the statistical package used for data analysis. Significant difference was set at p < 0.05.

    Oxidative stress markers, glutathione peroxidase (GPX) and Catalase, were evaluated in the brain of rat following the administration of vanadium to induce neurotoxicity.

    The results of the analysis show that exposure to VAN decreased glutathione peroxidase levels as seen in VAN group and treatment with Naringin was effective in improving GPX levels as seen in NAR+VAN group.

    Figure 1.  Bar chart representation showing changes in the brain GPX level following exposure to VAN and treatment with naringin. Comparison between groups by one-way ANOVA followed by Tukey's multiple comparison test shows a decrease in the brain glutathione peroxidase level in VAN group when compared with CTL group (**p < 0.01). Treatment with Naringin shows a significant increase in the brain glutathione levels in NAR+VAN group when compared to VAN group (*p < 0.05). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin+Vanadium group; VAN = vanadium group.

    The results of the analysis show that exposure to VAN decreased catalase levels as seen in VAN group and treatment with Naringin was effective in improving catalase levels as seen in NAR+VAN group.

    Figure 2.  Bar chart representation showing changes in the brain catalase level following exposure to VAN and treatment with naringin. Comparison between groups by one-way ANOVA followed by Tukey's multiple comparison test shows a significant decrease in the brain catalase level in VAN group when compared with CTL group (**p < 0.01). Treatment with Naringin increased the brain catalase levels in NAR+VAN group when compared to VAN group. There is equally a significant increase in the brain catalase level in rat exposed to just Naringin in the NAR group when compared to VAN group (*p < 0.05). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin + Vanadium group; VAN = vanadium group.

    Figure 3a revealed the efficacy of naringin in the substantia nigra of vanadium treated animals. Control and naringin group revealed a normal distribution of neuronal cell and a statistically significant increase in the cell count when compared to the vanadium group, which shows a reduction in the cell count. Naringin treated group demonstrated a statistically significant increase in the cell count when compared to the vanadium group. The slide below demonstrated the role of naringin in the caudate putamen of vanadium treated animals. Control and naringin group revealed a normal distribution of neuronal cell and a statistically significant increase in the cell count when compared to the vanadium group, which shows a reduction in the cell count. Naringin treated group demonstrated a statistically significant increase in the cell count when compared to the vanadium group (Figure 3b).

    Figure 3a.  Histoarchitectural changes and cell count of the Substantia Nigra (SNc) showing the neuronal cell morphology and distribution. CTL and NAR group revealed a normal distribution of neuronal cell as well as a statistically significant increase in the cell count when compared to vanadium treated group. VAN group showed neuronal cells undergoing apoptosis, and a statistically significant reduction in the count when compared to CTL. However, treatment with naringin was able to ameliorate the negative impact of vanadium. H&E. (Mag. x800; Scale bar: 51 µm), (***p < 0.001). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin + Vanadium group; VAN = vanadium group.
    Figure 3b.  Histoarchitectural changes and cell count of the Caudate Putamen (CPu) showing the neuronal cell morphology and distribution. CTL and NAR group revealed a normal distribution of neuronal cell as well as a statistically significant increase in the cell count when compared to vanadium treated group. VAN group showed neuronal cells undergoing apoptosis, and a statistically significant reduction in the count when compared to CTL. However, treatment with naringin was able to ameliorate the negative impact of vanadium. H&E. (Mag. x800; Scale bar: 51 µm), (***p < 0.001). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin + Vanadium group; VAN = vanadium group.

    Immunohistochemical study on caudate putamen and substantia nigra evaluating the positive impact of naringin following vanadium neurotoxicity.

    Figure 4a.  NeuN viable cells in the Substantia Nigra (SNc). CTL and NAR group revealed a lot of viable nerve cells as shown in the photomicrograph. In the NAR+VAN group and the VAN group very little amount of viable cells are visible. (Dark brownish round cells indicate the positive nerve cells). Bar chart representation showing the cell count of viable cells following exposure to VAN and treatment with naringin. Comparison between groups by one-way ANOVA followed by Tukey's multiple comparison test shows a significant decrease in viable cells in VAN group when compared with CTL group (***p < 0.001). Treatment with Naringin increased the immunopositive cell count in NAR+VAN group when compared to VAN group (***p < 0.001). There is equally an increase in the immunopositive cell count in rat exposed to just Naringin in the NAR group when compared to VAN group (***p < 0.001). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin + Vanadium group; VAN = vanadium group. (Mag. x800; Scale bar: 51 µm).
    Figure 4b.  Neun viable cells and Non-Viable cells in the Caudate Putamen (CPu). CTL and NAR group revealed many viable nerve cells as shown in the photomicrograph. In the NAR+VAN group and the VAN group very little amount of viable cells were seen. (Dark brownish round cells indicate viable nerve cells). Bar chart representation showing the cell count of viable cells following exposure to VAN and treatment with naringin. Comparison between groups by one-way ANOVA followed by Tukey's multiple comparison test shows a significant decrease in viable cells in VAN group when compared with CTL group (***p < 0.001). Treatment with Naringin increased the immunopositive cell count in NAR+VAN group when compared to VAN group (***p < 0.001). There is equally an increase in the immunopositive cell count in rat exposed to just Naringin in the NAR group when compared to VAN group (***p < 0.001). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin + Vanadium group; VAN = vanadium group. (Mag. x800; Scale bar: 51 µm).
    Figure 5a.  Inflammasome immunopositive cells in the Substantia Nigra (SNc). CTL and NAR group revealed less or no expression of inflammasome as shown in the photomicrograph. Expression of inflammasome cells are visible in the NAR+VAN group and the VAN group. (Dark brownish round cells indicate the immunopositive cells). Bar chart representation showing the cell count following exposure to VAN and treatment with naringin. Comparison between groups by one-way ANOVA followed by Tukey's multiple comparison test shows a significant increase in inflammasome in VAN group when compared with CTL group (***p < 0.001). Treatment with Naringin reduced the immunopositive cell count in NAR+VAN group when compared to VAN group (***p < 0.001). There is equally a significant reduction in the immunopositive cell count in rat exposed to just Naringin in the NAR group when compared to VAN group (***p < 0.001). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin + Vanadium group; VAN = vanadium group. (Mag. x800; Scale bar: 51 µm).
    Figure 5b.  Inflammasome immunopositive cells in the Caudate Putamen (CPu). CTL and NAR group revealed less or no expression of inflammasome as shown in the photomicrograph. Expression of inflammasome cells are visible in the NAR+VAN group and the VAN group. (Dark brownish round cells indicate the immunopositive cells). Bar chart representation showing the cell count following exposure to VAN and treatment with naringin. Comparison between groups by one-way ANOVA followed by Tukey's multiple comparison test shows a significant increase in inflammasome in VAN group when compared with CTL group (***p < 0.001). Treatment with Naringin reduced the immunopositive cell count in NAR+VAN group when compared to VAN group (***p < 0.001). There is equally a significant reduction in the immunopositive cell count in rat exposed to just Naringin in the NAR group when compared to VAN group (***p < 0.001). Legend: CTL = control group; NAR = naringin group; NAR + VAN = Naringin + Vanadium group; VAN = vanadium group. (Mag. x800; Scale bar: 51 µm).

    In this research, the motor benefit of Naringin in a mouse model of vanadium-induced neurotoxicity which is similar to parkinsonism is evaluated. Oxidative stress is one of the major factors contributing to Parkinson's disease, Naringin is beneficial because it is believed to be dopamine enhancing and a potent antioxidant. The data provided suggest that Naringin could have a beneficial effect in the treatment of motor deficit induced by vanadium.

    Oxidative stress is known to have an effect in neurodegenerative disorders like Parkinson's disease where damage to neurons can reflect both an increase in oxidative processes and a decrease in antioxidant defenses. Oxidative stress is defined as the imbalance between biochemical processes leading to the production of reactive oxygen species [9]. The ROS species like superoxide, hydrogen peroxide, and hydroxyl radical ions, oxidize the bio-chemicals and destroy lipids, DNA and RNA, which can then cause neurodegeneration [10]. In this study the effect of Naringin on the Catalase and Glutathione peroxidase (GPx) levels in the Substantia nigra and Caudate Putamen of rat brain after the exposure to vanadium was evaluated. GPx is one of the most abundant antioxidants that can be found in the brain, it is essential in the whole defense approach of antioxidants, more importantly as regards to superoxide anion radical (*O2) which is generated through mitochondrial energy synthesis pathway [22]. In the result, GPX levels significantly reduced when comparing the control group with Vanadium only group as seen in figure 1 (*P < 0.05). This result agrees with Adekeye et al. [8] that vanadium decreases GPx levels, which might be as a result of increase in the formation of free radicals which then causes oxidative stress. Following treatment with Naringin there was a significant increase in GPx level in the treated group NAR+VAN when compared to the neurotoxic group (VAN). This result agrees with Garabadu and Agrawal, [11] on the ability of Naringin to improve GPx levels in Parkinson's induced rat by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in neurons. Results from the catalase levels when comparing the control group to Parkinson's induced group (VAN) show a significant decreased level of catalase in the VAN group as seen in figure 2 (**P < 0.01). This result corresponds with Adebiyi et al. [12]. Treatment with Naringin brought about a statistically significant increase in the treated group NAR+VAN when compared to the VAN group. This is in accordance to sugumar et al. [13] as Naringin showed effectiveness in restoring catalase levels.

    From the histological slides of Substantia nigra (SNc) and Caudate Putamen (CPu), normal neuronal cells with centrally located nuclei are visible in control (CTL) and Naringin (NAR) group, Figure 3a and b. VAN group showed neuronal cells undergoing apoptosis, and a statistically significant reduction in the count when compared to CTL group (***P < 0.001). This result agrees with Folarin et al. [14] who stipulated that vanadium was able to reduce the neuronal cells in the brain following cell count as a result of the up-regulation of glia cells and this allows for apoptosis of neurons. The NAR+VAN group revealed neuronal cells undergoing recovery with centrally located nuclei and an increase in the count when compared to VAN group. This result agrees with Uddin et al. [15] that Naringin can act as an anti-apoptotic drug in neurodegeneration by inducing Glial cell line-derived neurotrophic factor (GDNF) which is a protein that allows for the survival of nerve cells that have been lost as a result of the induced neurotoxicity. It is evident from this study that vanadium causes degenerative changes in the Substantia nigra (SNc) and Caudate putamen (CPu) which involves loss of neuronal cells with impaired motor function, and this is in line with statement made in Nnama et al. [16].

    In Immunohistochemistry, NeuN and NLRP3 Inflammasome markers were used. Neuronal nuclear protein (NeuN) is expressed in the nuclei of majority of the nervous system neurons. It is regarded as an immunohistochemical marker commonly used for neurons. NeuN marks for viable and non-viable neurons and a comparisons between the groups can be achieved. NeuN immunohistochemistry is widely used to test for loss of phenotypic marker expression and cell-type specificity of the lesions in PD models [17]. In NeuN result of the Substantia Nigra (SNc) and the Caudate Putamen (CPu) control (CTL) and Naringin (NAR) revealed a large amount of viable cells with centrally located nuclei Figure 4a and 4b. In the NAR+VAN group and the VAN group there is visible amount of non-viable cells with VAN group having a significant higher number of non-viable cell and least amount of viable cells when compared to the NAR+VAN group (***P < 0.001). This result agrees with Zou et al. [18] that naringin can reduce neurodegeneration and restore neuronal development.

    NLRP3 inflammasome major role is to detect inflammation and immune system-related disorders, and also in the pathogenesis of several neurodegenerative diseases [19]. In this study it is used to check inflammation in the cells of the Substantia nigra (SNc) and Caudate Putamen (CPu). In the result of figure 5a and 5b, there is a significantly high amount of NLRP3 positive cells in the VAN group when compared to the CTL group (***P < 0.001). The result agrees with Im et al. [20] that vanadium increases the activation of NLRP3 in cells which might be as a result of Tumour Necrosis Factor alpha (TNF alpha) that is produced. In the Naringin treated group (NAR+VAN) there is a decreased number of NLRP3 positive cell in the SNc and CPu when compared to the Parkinson's induced group (VAN), this just shows that Naringin inhibits the activation of NLRP3 and production of Tumour Necrosis Factor alpha [21].

    The results from this study shows that vanadium was effective in altering motor function by lowering the antioxidant level, reducing neuronal cells and stimulating inflammation in adult Wistar rat, while, Naringin play an anti-oxidative and anti-inflammatory role by elevating the catalase and Glutathione peroxidase level, and reviving the neuronal cells and inflammatory cells.



    Conflict of interest



    All author declare no conflict of interest.

    Author contributions



    AOA conceived the conceptual idea. AAF, AEO and OSS conducted the experiments and planned the literature search. AAF and OOO analyzed and interpreted the data. AAF, AOA and LAE drafted the manuscript, read, and revised the manuscript. All authors gave the final approval for the manuscript to be published.

    [1] Ohiomokhare S, Olaolorun F, Ladagu A, et al. (2020) The Pathopharmacological Interplay between Vanadium and Iron in Parkinson's Disease Models. Int J Mol Sci 21: 6719. https://doi.org/10.3390/ijms21186719
    [2] Fatola OI, Olaolorun FA, Olopade FE, et al. (2019) Trends in vanadium neurotoxicity. Brain Res Bull 145: 75-80. https://doi.org/10.1016/j.brainresbull.2018.03.010
    [3] Onojake MC, Osuji LC, Abrakasa S (2015) Source, depositional environment and maturity levels of some crude oils in southwest Niger Delta, Nigeria. Chinese J Geochem 34: 224-232. https://doi.org/10.1007/s11631-015-0035-9
    [4] Lee AY, Lee MH, Lee S, et al. (2018) Neuroprotective effect of alpha-linolenic acid against Aβ-mediated inflammatory responses in C6 glial cell. J Agr Food Chem 66: 4853-4861. https://doi.org/10.1021/acs.jafc.8b00836
    [5] Ahmad S, Khan A, Ali W, et al. (2021) Fisetin rescues the mice brains against D-galactose-induced oxidative stress, neuroinflammation and memory impairment. Front Pharmacol 12: 612078. https://doi.org/10.3389/fphar.2021.612078
    [6] Zaidun NH, Thent ZC, Abd Latiff A (2018) Combating oxidative stress disorders with citrus flavonoid: Naringenin. Life Sci 208: 111-122. https://doi.org/10.1016/j.lfs.2018.07.017
    [7] Yang Y, Wu Y, Zou J, et al. (2021) Naringenin attenuates non-alcoholic fatty liver disease by enhancing energy expenditure and regulating autophagy via AMPK. Front Pharmacol 12: 687095. https://doi.org/10.3389/fphar.2021.687095
    [8] Adekeye AO, Irawo GJ, Fafure AA (2020) Ficus exasperata Vahl leaves extract attenuates motor deficit in vanadium-induced parkinsonism mice. Anat Cell Biol 53: 183-193. https://doi.org/10.5115/acb.19.205
    [9] Sayre LM, Perry G, Smith MA (2008) Oxidative stress and neurotoxicity. Chem Res Toxicol 21: 172-188. https://doi.org/10.1021/tx700210j
    [10] Mir NT, Saleem U, Anwar F, et al. (2019) Lawsonia Inermis markedly improves cognitive functions in animal models and modulate oxidative stress markers in the brain. Medicina 55: 192. https://doi.org/10.3390/medicina55050192
    [11] Garabadu D, Agrawal N (2020) Naringin exhibits neuroprotection against rotenone-induced neurotoxicity in experimental rodents. NeuroMolecular Medcine 22: 314-330. https://doi.org/10.1007/s12017-019-08590-2
    [12] Adebiyi OE, Olayemi FO, Olopade JO, et al. (2019) Βeta-sitosterol enhances motor coordination, attenuates memory loss and demyelination in a vanadium-induced model of experimental neurotoxicity. Pathophysiology 26: 21-29. https://doi.org/10.1016/j.pathophys.2018.12.002
    [13] Sugumar M, Sevanan M, Sekar S (2019) Neuroprotective effect of naringenin against MPTP-induced oxidative stress. Int J Neurosci 129: 534-539. https://doi.org/10.1080/00207454.2018.1545772
    [14] Folarin OR, Adaramoye OA, Akanni OO, et al. (2018) Changes in the brain antioxidant profile after chronic vanadium administration in mice. Metabolic Brain Disease 33: 377-385. https://doi.org/10.1007/s11011-017-0070-9
    [15] Uddin MS, Mamun AA, Rahman MM, et al. (2021) Natural products for neurodegeneration: regulating neurotrophic signals. Oxid Med Longev 2021. https://doi.org/10.1155/2021/8820406
    [16] Nnama AU, Ekeh FN, Aguzie IO, et al. (2022) Vanadium pentoxide induces hematological, oxidative stress and histological changes in Oryctolagus cuniculus. J Hazard Mater Adv 5: 100048. https://doi.org/10.1016/j.hazadv.2022.100048
    [17] Cannon JR, Greenamyre JT (2009) NeuN is not a reliable marker of dopamine neurons in rat substantia nigra. Neurosci Lett 464: 14-17. https://doi.org/10.1016/j.neulet.2009.08.023
    [18] Zou L, Ning M, Wang W, et al. (2020) Naringenin Prevents Propofol Induced Neurodegeneration in Neonatal Mice Brain and Long-Term Neurocognitive Impacts on Adults. Drug Des Dev Ther 14: 5469. https://doi.org/10.2147/DDDT.S280443
    [19] Paldino E, D'Angelo V, Sancesario G, et al. (2020) Pyroptotic cell death in the R6/2 mouse model of Huntington's disease: new insight on the inflammasome. Cell Death Discov 6: 1-12. https://doi.org/10.1038/s41420-020-00293-z
    [20] Im H, Kim E, Kwon HJ, et al. (2022) Therapeutic effect of silibinin on vanadium-induced chronic lung injury in mice. PREPRINT (Version 1) available at Research Square . https://doi.org/10.21203/rs.3.rs-1548568/v1
    [21] Cao H, Liu J, Shen P, et al. (2018) Protective effect of naringin on DSS-induced ulcerative colitis in mice. J Agr Food Chem 66: 13133-13140. https://doi.org/10.1021/acs.jafc.8b03942
    [22] Calabrese V, Mancuso C, Calvani M, et al. (2007) Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8: 766-775. https://doi.org/10.1038/nrn2214
  • This article has been cited by:

    1. María Eugenia Cervantes-Valencia, Nelly López-Valdez, Marcela Rojas-Lemus, Adriana González-Villalva, Guadalupe Morales-Ricardes, Patricia Bizarro-Nevares, Martha Ustarroz-Cano, José Ángel Salgado-Hernández, Shamir Mendoza-Martínez, Laura Michelle Lamas Orozco, Teresa I. Fortoul, Antioxidantes naturales y su efecto contra el estrés oxidante provocado por la contaminación por material particulado, 2024, 67, 24484865, 7, 10.22201/fm.24484865e.2024.67.4.02
    2. Yan-Lin Ma, Jie Deng, Ting Zhang, Hong-Mei Li, Qiu-Zhe Liang, Kai-Lin Zhang, Enhanced expression of RAGE/NADPH oxidase signaling pathway and increased level of oxidative stress in brains of rats with chronic fluorosis and the protective effects of blockers, 2023, 80, 0946672X, 127288, 10.1016/j.jtemb.2023.127288
    3. Youyang Zhu, Miao Tian, Shiyu Lu, Yuliang Qin, Ting Zhao, Hongling Shi, Zhaofu Li, Dongdong Qin, The Antioxidant Role of Aromatic Plant Extracts in Managing Neurodegenerative Diseases: A Comprehensive Review, 2025, 03619230, 111253, 10.1016/j.brainresbull.2025.111253
  • Reader Comments
  • © 2022 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(1967) PDF downloads(103) Cited by(3)

Figures and Tables

Figures(8)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog