Quercetin and brain health -
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Ferri, P. Enhancement of flavonoid ability to cross the blood-brain barrier of rats by co-administration with [small alpha]-tocopherol. The immunofluorescence results showed the increased intensity of GFAP-positive cells and immunofluorescence reactivity in the LPS-treated group compared to the control groups.
Quercetin treatment along with LPS significantly reduced the GFAP-positive cells and immunofluorescence reactivity compared to LPS-treated mice Figure 4C. Figure 4. Quercetin ameliorated LPS-induced activated gliosis in the cortex and hippocampus of adult mice.
A,B Western blotting of the proteins GFAP and Iba-1; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
Mounting studies have demonstrated that LPS is known to activate microglia in several animal models, which leads to neuroinflammation and neurodegeneration Johansson et al. TLR-4 is a primary receptor for LPS-activated microglia Qin et al. Here, we also found through western blotting that systemic administration of LPS activated TLR-4 in the adult mouse cortex and hippocampus compared to the control group of mice.
Quercetin treatment along with LPS significantly decreased the expression of TLR-4 in the mouse cortex and hippocampus compared to LPS-treated mice Figures 5A,B. Activated TLR-4 is responsible for inflammatory signaling in the MyDdependent pathway, which is responsible for the up-regulation of p-NF-κB and ultimately leads to neuroinflammation and neurodegeneration Yao et al.
We also found through western blotting that LPS administration activated p-NF-κB expression in the cortex and hippocampus of adult mice compared to the control group of mice.
Treatment with quercetin significantly reduced the expression of p-NF-κB in the cortex and hippocampus of adult mice Figures 5A,B. Figure 5. A,B Western blotting of TLR4 and p-NFKB proteins; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
Furthermore, the immunofluorescence results of p-NF-κB showed immunofluorescence reactivity in the LPS-treated group compared to the control groups. Quercetin treatment along with LPS significantly reduced the immunofluorescence reactivity compared to LPS-treated mice Figure 5C. Quercetin is a natural flavonoid found in many vegetables and fruits and possesses potential biological and health beneficial effects that have the ability to inhibit inflammatory mediators Lesjak et al.
It has been reported that LPS administration has the potential to increase the production of several inflammatory mediators, such as TNF-α, COX-2, NOS-2, and IL-1β Badshah et al. Here, we also ascertained through western blotting that LPS administration increased the expression of TNF-α, COX-2, and NOS-2 in the cortex and hippocampus of adult mice compared to the control group of mice.
Quercetin treatment along with LPS significantly tempered and reduced the expression of these inflammatory proteins Figures 6A,B. Similarly, the immunofluorescence results of IL-1β showed that LPS administration increased the number of IL-1β-positive cells compared to control mice in the cortex and DG region, but the group of mice that received quercetin along with LPS significantly downregulated the IL-1β-positive cells and fluorescence immunoreactivity in the cortex and DG region Figure 6C.
Figure 6. Quercetin attenuated LPS-induced neuroinflammation-associated markers. A,B Western blotting of TNF-α, COX-2 and NOS2 proteins; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
The mitochondrial apoptotic pathway plays a key role in neuronal degeneration. In the mitochondrial apoptotic pathway, the antiapoptotic Bcl-2 and proapoptotic Bax markers have a primary role in the apoptotic pathway.
c, an important mediator in the mitochondrial associated pathway, which leads to activation of caspases Li et al. Previous studies Badshah et al. c compared to the control group. c expression level compared to the LPS-treated group alone.
In apoptotic neurodegeneration, the caspase family plays an important role. Among caspase cascades, caspase-3 is the major player in apoptosis and plays a key role in apoptosis Le et al.
Therefore, we also evaluated caspase-3 activity by western blotting and confocal microscopy. Our western blot results show that LPS activated caspase-3 activity in the cortex and hippocampus of adult mice compared to the control group of mice. Treatment with quercetin along with LPS significantly reduced the activated caspase-3 activity compared to LPS-treated mice Figures 7A,B.
Similarly, the confocal microscopy results showed that there are more caspasepositive cells and fluorescence reactivity of caspase-3 in the cortex and CA-1 region of the LPS-received mice compared to the control group of mice. However, treatment with quercetin significantly reduced caspasepositive cells and fluorescence immunoreactivity in the cortex and CA-1 region of the brain Figure 7C.
Figure 7. LPS-induced neuronal apoptotic pathway prevented by quercetin in the cortex and hippocampus. A,B Western blotting of Bcl-2, Bax, Cyto. c, Caspase-3 and PARP-1 proteins; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
D Representative immunohistochemical images Nissl staining and the quantified histogram of the survival neuron reactivity and integrated density in the cortex and hippocampus region of adult mice. PARP-1is a nuclear enzyme with a wide range of physiological and pathological functions.
In physiological function, it is involved in DNA repair and genomic stability. In pathological conditions, the over activation of PARP-1 leads to neuronal cell death Berger, ; Chaitanya et al. It has been reported that activated caspase-3 increased the over activation of PARP-1 Williams et al.
Therefore, in this context, we also evaluated the expression of PARP-1 through western blotting in both the cortex and hippocampus of adult mice.
Our western blotting results revealed that systemic LPS administration results in the overexpression of PARP-1 in the cortex and hippocampus of adult mice compared to the control group of mice.
Treatment with quercetin along with LPS reduced the expression of PARP-1 in the adult mouse cortex and hippocampus Figures 7A,B. Furthermore, the immunohistochemical Nissl staining results showed that LPS injection decreased the neuronal survival reactivity in the cortex and hippocampus of adult mouse brains compared to the control group of mice.
Importantly, quercetin administration to LPS-injected mice enhanced the survival of neuronal cells in the cortex and hippocampus of adult mouse brains Figure 7D.
The application and consumption of natural substances is a primary focus for the prevention of neurodegenerative diseases. Among natural substances, polyphenol-derived medicinal substances are important therapeutic agents for the slowing or prevention of neurological disorders Dajas et al.
Quercetin is a well-approved and recommended flavonoid that has medicinal properties and protective roles in different paradigms of CNS insult-induced detrimental effects Lei et al. Chronic neuroinflammation is a pathological cascade that occurs during the progression of several neurological disorders, such as AD, PD, FTD, and amyotrophic lateral sclerosis ALS Glass et al.
In chronic neuroinflammation, activated microglia and astrocytes disturb homeostasis and are implicated in all degenerative conditions of the CNS Netea et al.
Previous studies have shown that systemic administration of LPS activates microglia and astrocytes Qin et al. The TLR family has a promising and key role in the immune response. This family comprises 13 members in rodents and 11 members in humans. Furthermore, several studies have confirmed that TLR-4 is a primary target and receptor in glial cells Shimazu et al.
In both in vivo and in vitro evidence confirmed that LPS binds to TLR-4, inducing activated gliosis, which consequently mediates NF-kB cascade activation, which plays a serious role in the activation of inflammation and neurodegeneration processes Chen et al.
NF-kB has been considered a mediator between neuroinflammation and neurodegeneration. Several studies reported that natural flavonoids prevented activated gliosis by inhibiting completely or partially by inhibiting the TLR4 and NF-kB cascades Lee et al.
The inhibition of the TLR4 and NF-kB cascades confers desirable effects in any pathogenic and neurotoxic condition. Bureau et al. Likewise, we have found that quercetin administration prevents LPS-induced activated gliosis by reducing the expression of TLR4 and NF-kB cascades. Activated microglia and astrocytes are responsible for the release of inflammatory molecules such as TNF-α, IL-1β, COX-2, and NOS2, which are responsible for neuroinflammation.
Studies have reported that activated nuclear translocation of the NF-kB cascades pathway is implicated in the over production and release of the above proinflammatory mediators Li and Verma, ; Lee et al. In a literature review reported that transgenic rodents that overexpressed TNF-α exhibited inflammation and neurodegeneration, which lead to memory impairment.
Over activation of TNF-α has been reported to induce neurotoxicity in human cortical neurons. Similarly, mounting studies have reported overexpressed immunoreactive IL-1β cells in pathogenic conditions, brain injuries and degeneration. Overexpressed IL-1β affects both neuronal and non-neuronal cells in the CNS Wyss-Coray and Rogers In addition, when murine BV2 microglial cells are exposed to LPS- and IFN-γ-induced NO production and iNOS gene expression, neuroinflammation-mediated neurodegeneration is triggered Chen et al.
TNF-α, IL-1β and reactive species such NO and iNOS induced the overexpression of COX2, which has a key role in the intensification of neuroinflammation-mediated neurodegeneration Feng et al.
Recent attention has been given to natural compounds such as flavonoids that possess multiple neuroprotective activities, such as suppressing neuroinflammation and neuronal apoptosis, and promoting neuronal survival and memory enhancing effect Lee et al.
Flavonoids have been suggested as promising therapeutic agents for the reduction of neuroinflammation Magalingam et al. Quercetin is found abundantly in onions and various berries. Studies have reported that quercetin shows strong activity against neuroinflammation Spencer, ; Kanter et al.
In the present study, our results supported the previous findings and elucidated that quercetin suppressed the proinflammatory mediators as described above and consequently attenuated LPS-induced neuroinflammation in the adult mouse cortex and hippocampus.
Chronic neuroinflammation mediates the neuronal degeneration process in various diseases, such as AD, PD, and ALS. In both in vivo and in vitro studies, LPS-induced activated cytokines and chemokines as well as activated redox and nitrogen species, which further trigger apoptotic neurodegeneration Li and Verma, ; Chen et al.
c, which further triggers the activation of caspase cascades. Caspase cascades, e. The activation of caspase-3 induced neuronal cell death and has been considered a main feature of neurodegenerative diseases. Activated caspase-3 cleaves PARP-1, which leads to neuronal DNA damage Le et al.
The natural dietary flavonoid shows a protective role against CNS-insult-induced neurodegeneration. Quercetin is a natural flavonoid that inhibits neuronal apoptotic cell death Bureau et al. Interestingly, quercetin also regulated the mitochondrial apoptotic pathway and prevented the activation of Cyto.
c, activated caspase 3 and cleaved PARP-1 expression and subsequently prevents neuronal degeneration, demonstrating that neuroinflammation-mediated neurodegeneration is rescued by quercetin.
It has been studied that systemic administration of LPS triggers neuroinflammation-mediated neurodegeneration, which is responsible for synaptic and memory dysfunction Qin et al. Flavonoids have been investigated well for improving learning and memory functions in aberrant and detrimental conditions Scapagnini et al.
Studies show that LPS administration is responsible for decreasing the level of presynaptic and postsynaptic proteins Badshah et al.
Our results also claimed that the systemic administration of LPS decreased the level of presynaptic proteins synaptophysin and postsynaptic protein PSD in the mouse cortex and hippocampus. Our results show that quercetin treatment alleviates the LPS-induced impairment of synaptic functions in the mouse cortex and hippocampus.
Similarly, we also observed that systemic LPS administration induced memory dysfunction. This memory dysfunction in the LPS-treated mice was reversed by quercetin, indicating that quercetin would be beneficial to improve the memory functions associated with synaptic functions in CNS-insult-induced detrimental effects.
These results suggest that drugs of natural origin with significant potential biological activity would be beneficial against pathogenic and neuronal insults in neurological disorders. AK designed and managed the experimental work, and wrote the manuscript.
TA contributed in the manuscript writing. AK, HB, SR, SA, KS, MI, TM, and MSK performed the western blot and morphological experiments. MOK was the corresponding author, having reviewed and approved the manuscript, and holds all the responsibilities related to this manuscript.
All authors reviewed the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Quercetin is Blood sugar and overall well-being type of plant Metabolic health newsletter known as Qurecetin flavonoid. Quercetin is also available in supplement Quercetin and brain health. Quercetin is an antioxidant and hhealth anti-inflammatory effects brainn may help reduce swelling, regulate Preventing ulcerative colitis sugar Quercetin and brain health, and prevent heart disease. Research shows that supplemental quercetin may also protect brain health, support immune function, and aid weight management. Dietary supplements are minimally regulated by the FDA and may or may not be suitable for you. The effects of supplements vary from person to person and depend on many variables, including type, dosage, frequency of use, and interactions with current medications. Please speak with your healthcare provider or pharmacist before starting any supplements.Quercetin and brain health -
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B The average number of crossings at the hidden platform during the probe test of the MWM test. C Time spent in the platform quadrant, where the hidden platform was placed during the trial session. The Y-maze results also indicated that LPS triggered short-term spatial memory dysfunction compared to the control group.
Quercetin treatment significantly enhanced the spontaneous alteration behavior percentage a parameter for the enhancement of spatial working memory functions , indicating that quercetin improved the spatial working memory function of the LPS-injected mice Figure 2D.
Mounting studies have reported that flavonoids are beneficial for synaptic and memory functions Ahmad et al. Because synaptic pre- and postsynaptic proteins have been associated with the decline of memory and cognitive functions.
Therefore, we also examined the effects of quercetin on synaptic expression levels by western blot and confocal microscopy. The western blot Figures 3A,B results show that the group of mice that received LPS had decreased expression levels of PSD and Synap in the cortex and hippocampus compared to the control group of adult mice.
Treatment with quercetin along with LPS significantly reversed the LPS-induced synaptic deficit by increasing the expression of PSD95 and Synap in the cortex and hippocampus of adult mice Figures 3A,B.
To further verify the effect of quercetin on synaptic function, we examined SNAP expression levels using confocal microscopy. The immunofluorescence images showed reduced reactivity in the LPS-treated mice compared to the control group. Quercetin treatment significantly increased the immunofluorescence reactivity of SNAP in the cortex and DG region of the hippocampus compared to the LPS-treated group of adult mice Figure 3C.
Figure 3. Quercetin improved the pre- and postsynaptic markers in the LPS-treated mice. A,B Western blotting of the proteins Synap and PSD95; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
β-Actin was used as a loading control. The quantified density values are shown in arbitrary units A. Magnified 10×. The expressed data are relative to the control. Microglia and astrocytes in the CNS respond rapidly to complaints such as infections, stress, and injury, which makes them important modulators of neuroinflammation responses Witte et al.
Studies have reported that in systemic LPS administration, activated microglia and astrocytes are responsible for neuroinflammation-mediated neurodegeneration Qin et al.
GFAP protein and Iba-1 are specific markers for activated astrocytes and microglia, respectively. Flavonoids, on the other hand, have been reported to have multiple neuroprotective properties, including potent anti-inflammatory effects.
Quercetin, a natural flavonoid, also shows a strong anti-inflammatory action by suppressing activated astrocytosis and microgliosis Chen et al.
To analyze the expression of GFAP and Iba-1, we found through western blotting that LPS treatment significantly increased the expression of these two proteins in the adult mouse cortex and hippocampus compared to the control group of mice.
Treatment with quercetin along with LPS significantly decreased the expression of these proteins in the adult mouse cortex and hippocampus Figures 4A,B.
In addition, the GFAP expression level was also analyzed using immunofluorescence staining. The immunofluorescence results showed the increased intensity of GFAP-positive cells and immunofluorescence reactivity in the LPS-treated group compared to the control groups.
Quercetin treatment along with LPS significantly reduced the GFAP-positive cells and immunofluorescence reactivity compared to LPS-treated mice Figure 4C. Figure 4. Quercetin ameliorated LPS-induced activated gliosis in the cortex and hippocampus of adult mice.
A,B Western blotting of the proteins GFAP and Iba-1; their differences in the cortex and hippocampus of mouse brains are represented by a histogram. Mounting studies have demonstrated that LPS is known to activate microglia in several animal models, which leads to neuroinflammation and neurodegeneration Johansson et al.
TLR-4 is a primary receptor for LPS-activated microglia Qin et al. Here, we also found through western blotting that systemic administration of LPS activated TLR-4 in the adult mouse cortex and hippocampus compared to the control group of mice.
Quercetin treatment along with LPS significantly decreased the expression of TLR-4 in the mouse cortex and hippocampus compared to LPS-treated mice Figures 5A,B.
Activated TLR-4 is responsible for inflammatory signaling in the MyDdependent pathway, which is responsible for the up-regulation of p-NF-κB and ultimately leads to neuroinflammation and neurodegeneration Yao et al. We also found through western blotting that LPS administration activated p-NF-κB expression in the cortex and hippocampus of adult mice compared to the control group of mice.
Treatment with quercetin significantly reduced the expression of p-NF-κB in the cortex and hippocampus of adult mice Figures 5A,B. Figure 5. A,B Western blotting of TLR4 and p-NFKB proteins; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
Furthermore, the immunofluorescence results of p-NF-κB showed immunofluorescence reactivity in the LPS-treated group compared to the control groups. Quercetin treatment along with LPS significantly reduced the immunofluorescence reactivity compared to LPS-treated mice Figure 5C.
Quercetin is a natural flavonoid found in many vegetables and fruits and possesses potential biological and health beneficial effects that have the ability to inhibit inflammatory mediators Lesjak et al.
It has been reported that LPS administration has the potential to increase the production of several inflammatory mediators, such as TNF-α, COX-2, NOS-2, and IL-1β Badshah et al.
Here, we also ascertained through western blotting that LPS administration increased the expression of TNF-α, COX-2, and NOS-2 in the cortex and hippocampus of adult mice compared to the control group of mice. Quercetin treatment along with LPS significantly tempered and reduced the expression of these inflammatory proteins Figures 6A,B.
Similarly, the immunofluorescence results of IL-1β showed that LPS administration increased the number of IL-1β-positive cells compared to control mice in the cortex and DG region, but the group of mice that received quercetin along with LPS significantly downregulated the IL-1β-positive cells and fluorescence immunoreactivity in the cortex and DG region Figure 6C.
Figure 6. Quercetin attenuated LPS-induced neuroinflammation-associated markers. A,B Western blotting of TNF-α, COX-2 and NOS2 proteins; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
The mitochondrial apoptotic pathway plays a key role in neuronal degeneration. In the mitochondrial apoptotic pathway, the antiapoptotic Bcl-2 and proapoptotic Bax markers have a primary role in the apoptotic pathway. c, an important mediator in the mitochondrial associated pathway, which leads to activation of caspases Li et al.
Previous studies Badshah et al. c compared to the control group. c expression level compared to the LPS-treated group alone. In apoptotic neurodegeneration, the caspase family plays an important role. Among caspase cascades, caspase-3 is the major player in apoptosis and plays a key role in apoptosis Le et al.
Therefore, we also evaluated caspase-3 activity by western blotting and confocal microscopy. Our western blot results show that LPS activated caspase-3 activity in the cortex and hippocampus of adult mice compared to the control group of mice. Treatment with quercetin along with LPS significantly reduced the activated caspase-3 activity compared to LPS-treated mice Figures 7A,B.
Similarly, the confocal microscopy results showed that there are more caspasepositive cells and fluorescence reactivity of caspase-3 in the cortex and CA-1 region of the LPS-received mice compared to the control group of mice. However, treatment with quercetin significantly reduced caspasepositive cells and fluorescence immunoreactivity in the cortex and CA-1 region of the brain Figure 7C.
Figure 7. LPS-induced neuronal apoptotic pathway prevented by quercetin in the cortex and hippocampus. A,B Western blotting of Bcl-2, Bax, Cyto. c, Caspase-3 and PARP-1 proteins; their differences in the cortex and hippocampus of mouse brains are represented by a histogram.
D Representative immunohistochemical images Nissl staining and the quantified histogram of the survival neuron reactivity and integrated density in the cortex and hippocampus region of adult mice. PARP-1is a nuclear enzyme with a wide range of physiological and pathological functions.
In physiological function, it is involved in DNA repair and genomic stability. In pathological conditions, the over activation of PARP-1 leads to neuronal cell death Berger, ; Chaitanya et al.
It has been reported that activated caspase-3 increased the over activation of PARP-1 Williams et al. Therefore, in this context, we also evaluated the expression of PARP-1 through western blotting in both the cortex and hippocampus of adult mice.
Our western blotting results revealed that systemic LPS administration results in the overexpression of PARP-1 in the cortex and hippocampus of adult mice compared to the control group of mice. Treatment with quercetin along with LPS reduced the expression of PARP-1 in the adult mouse cortex and hippocampus Figures 7A,B.
Furthermore, the immunohistochemical Nissl staining results showed that LPS injection decreased the neuronal survival reactivity in the cortex and hippocampus of adult mouse brains compared to the control group of mice.
Importantly, quercetin administration to LPS-injected mice enhanced the survival of neuronal cells in the cortex and hippocampus of adult mouse brains Figure 7D. The application and consumption of natural substances is a primary focus for the prevention of neurodegenerative diseases.
Among natural substances, polyphenol-derived medicinal substances are important therapeutic agents for the slowing or prevention of neurological disorders Dajas et al.
Quercetin is a well-approved and recommended flavonoid that has medicinal properties and protective roles in different paradigms of CNS insult-induced detrimental effects Lei et al. Chronic neuroinflammation is a pathological cascade that occurs during the progression of several neurological disorders, such as AD, PD, FTD, and amyotrophic lateral sclerosis ALS Glass et al.
In chronic neuroinflammation, activated microglia and astrocytes disturb homeostasis and are implicated in all degenerative conditions of the CNS Netea et al.
Previous studies have shown that systemic administration of LPS activates microglia and astrocytes Qin et al. The TLR family has a promising and key role in the immune response.
This family comprises 13 members in rodents and 11 members in humans. Furthermore, several studies have confirmed that TLR-4 is a primary target and receptor in glial cells Shimazu et al.
In both in vivo and in vitro evidence confirmed that LPS binds to TLR-4, inducing activated gliosis, which consequently mediates NF-kB cascade activation, which plays a serious role in the activation of inflammation and neurodegeneration processes Chen et al.
NF-kB has been considered a mediator between neuroinflammation and neurodegeneration. Several studies reported that natural flavonoids prevented activated gliosis by inhibiting completely or partially by inhibiting the TLR4 and NF-kB cascades Lee et al.
The inhibition of the TLR4 and NF-kB cascades confers desirable effects in any pathogenic and neurotoxic condition. Bureau et al. Likewise, we have found that quercetin administration prevents LPS-induced activated gliosis by reducing the expression of TLR4 and NF-kB cascades.
Activated microglia and astrocytes are responsible for the release of inflammatory molecules such as TNF-α, IL-1β, COX-2, and NOS2, which are responsible for neuroinflammation.
Studies have reported that activated nuclear translocation of the NF-kB cascades pathway is implicated in the over production and release of the above proinflammatory mediators Li and Verma, ; Lee et al. In a literature review reported that transgenic rodents that overexpressed TNF-α exhibited inflammation and neurodegeneration, which lead to memory impairment.
Over activation of TNF-α has been reported to induce neurotoxicity in human cortical neurons. Similarly, mounting studies have reported overexpressed immunoreactive IL-1β cells in pathogenic conditions, brain injuries and degeneration. Overexpressed IL-1β affects both neuronal and non-neuronal cells in the CNS Wyss-Coray and Rogers In addition, when murine BV2 microglial cells are exposed to LPS- and IFN-γ-induced NO production and iNOS gene expression, neuroinflammation-mediated neurodegeneration is triggered Chen et al.
TNF-α, IL-1β and reactive species such NO and iNOS induced the overexpression of COX2, which has a key role in the intensification of neuroinflammation-mediated neurodegeneration Feng et al.
Recent attention has been given to natural compounds such as flavonoids that possess multiple neuroprotective activities, such as suppressing neuroinflammation and neuronal apoptosis, and promoting neuronal survival and memory enhancing effect Lee et al.
Flavonoids have been suggested as promising therapeutic agents for the reduction of neuroinflammation Magalingam et al. Quercetin is found abundantly in onions and various berries.
Studies have reported that quercetin shows strong activity against neuroinflammation Spencer, ; Kanter et al. In the present study, our results supported the previous findings and elucidated that quercetin suppressed the proinflammatory mediators as described above and consequently attenuated LPS-induced neuroinflammation in the adult mouse cortex and hippocampus.
Chronic neuroinflammation mediates the neuronal degeneration process in various diseases, such as AD, PD, and ALS. In both in vivo and in vitro studies, LPS-induced activated cytokines and chemokines as well as activated redox and nitrogen species, which further trigger apoptotic neurodegeneration Li and Verma, ; Chen et al.
c, which further triggers the activation of caspase cascades. Caspase cascades, e. The activation of caspase-3 induced neuronal cell death and has been considered a main feature of neurodegenerative diseases.
Activated caspase-3 cleaves PARP-1, which leads to neuronal DNA damage Le et al. The natural dietary flavonoid shows a protective role against CNS-insult-induced neurodegeneration. Quercetin is a natural flavonoid that inhibits neuronal apoptotic cell death Bureau et al.
Interestingly, quercetin also regulated the mitochondrial apoptotic pathway and prevented the activation of Cyto. c, activated caspase 3 and cleaved PARP-1 expression and subsequently prevents neuronal degeneration, demonstrating that neuroinflammation-mediated neurodegeneration is rescued by quercetin.
It has been studied that systemic administration of LPS triggers neuroinflammation-mediated neurodegeneration, which is responsible for synaptic and memory dysfunction Qin et al. Flavonoids have been investigated well for improving learning and memory functions in aberrant and detrimental conditions Scapagnini et al.
Studies show that LPS administration is responsible for decreasing the level of presynaptic and postsynaptic proteins Badshah et al. Our results also claimed that the systemic administration of LPS decreased the level of presynaptic proteins synaptophysin and postsynaptic protein PSD in the mouse cortex and hippocampus.
Our results show that quercetin treatment alleviates the LPS-induced impairment of synaptic functions in the mouse cortex and hippocampus. Similarly, we also observed that systemic LPS administration induced memory dysfunction.
This memory dysfunction in the LPS-treated mice was reversed by quercetin, indicating that quercetin would be beneficial to improve the memory functions associated with synaptic functions in CNS-insult-induced detrimental effects. These results suggest that drugs of natural origin with significant potential biological activity would be beneficial against pathogenic and neuronal insults in neurological disorders.
AK designed and managed the experimental work, and wrote the manuscript. TA contributed in the manuscript writing. AK, HB, SR, SA, KS, MI, TM, and MSK performed the western blot and morphological experiments.
MOK was the corresponding author, having reviewed and approved the manuscript, and holds all the responsibilities related to this manuscript. All authors reviewed the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Ahmad, A. doi: PubMed Abstract CrossRef Full Text Google Scholar. Ali, T. Pineal Res. Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus.
Aravalli, R. Toll-like receptors in defense and damage of the central nervous system. NeuroImmune Pharmacol. Ashrafpour, M. CrossRef Full Text Google Scholar. Badshah, H. Co-treatment with anthocyanins and vitamin C ameliorates ethanol-induced neurodegeneration via modulation of GABAB receptor signaling in the adult rat brain.
CNS Neurol. Drug Targets 14, —
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