Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s Disease
The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ<sub>1</sub>–<sub>42</sub>)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For the development of an AD mouse model, amyl...
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MDPI AG
2021-09-01
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| author | Sareer Ahmad Myeung Hoon Jo Muhammad Ikram Amjad Khan Myeong Ok Kim |
| author_facet | Sareer Ahmad Myeung Hoon Jo Muhammad Ikram Amjad Khan Myeong Ok Kim |
| author_sort | Sareer Ahmad |
| collection | DOAJ |
| description | The current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ<sub>1</sub>–<sub>42</sub>)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For the development of an AD mouse model, amyloid-beta (Aβ<sub>1</sub>–<sub>42</sub>, 5 μL/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice’s brain by using a stereotaxic frame. After that, the mice were treated with Luteolin for two weeks at a dose of 80 mg/kg/day. To monitor the biochemical changes, we conducted western blotting and immunofluorescence analysis. According to our findings, the infusion of amyloid-beta activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental mice; these changes were significantly inhibited in Aβ<sub>1</sub>–<sub>42</sub> + Luteolin-treated mice. Likewise, we also checked the expression of inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB p65 (Ser536), tissue necrosis factor (TNF-α), and Interleukin1-β (IL-1β), in Aβ<sub>1</sub>–<sub>42</sub>-injected mice brain, which was attenuated in Aβ<sub>1</sub>–<sub>42</sub> + Luteolin-treated mice brains. Further, we investigated the expression of pro- and anti-apoptotic cell death markers such as Bax, Bcl-2, Caspase-3, and Cox-2, which was significantly reduced in Aβ<sub>1</sub>–<sub>42</sub> + Lut-treated mice brains compared to the brains of the Aβ-injected group. The results also indicated that with the administration of Aβ<sub>1</sub>–<sub>42</sub>, the expression levels of β-site amyloid precursor protein cleaving enzyme (BACE-1) and amyloid-beta (Aβ<sub>1</sub>–<sub>42</sub>) were significantly enhanced, while they were reduced in Aβ<sub>1</sub>–<sub>42</sub> + Luteolin-treated mice. We also checked the expression of synaptic markers such as PSD-95 and SNAP-25, which was significantly enhanced in Aβ<sub>1</sub>–<sub>42</sub> + Lut-treated mice. To unveil the underlying factors responsible for the protective effects of Luteolin against AD, we used a specific JNK inhibitor, which suggested that Luteolin reduced Aβ-associated neuroinflammation and neurodegeneration via inhibition of JNK. Collectively, our results indicate that Luteolin could serve as a novel therapeutic agent against AD-like pathological changes in mice. |
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| language | English |
| last_indexed | 2024-03-10T08:09:42Z |
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| spelling | doaj.art-5314489edb2f45e7ae97dc10ae81eb5a2023-11-22T10:45:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012217958310.3390/ijms22179583Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s DiseaseSareer Ahmad0Myeung Hoon Jo1Muhammad Ikram2Amjad Khan3Myeong Ok Kim4Division of Life Science and Applied Life Science (BK21 Four), College of Natural Sciences, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Science and Applied Life Science (BK21 Four), College of Natural Sciences, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Science and Applied Life Science (BK21 Four), College of Natural Sciences, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Science and Applied Life Science (BK21 Four), College of Natural Sciences, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Science and Applied Life Science (BK21 Four), College of Natural Sciences, Gyeongsang National University, Jinju 52828, KoreaThe current study was undertaken to unveil the protective effects of Luteolin, a natural flavonoid, against amyloid-beta (Aβ<sub>1</sub>–<sub>42</sub>)-induced neuroinflammation, amyloidogenesis, and synaptic dysfunction in mice. For the development of an AD mouse model, amyloid-beta (Aβ<sub>1</sub>–<sub>42</sub>, 5 μL/5 min/mouse) oligomers were injected intracerebroventricularly (i.c.v.) into mice’s brain by using a stereotaxic frame. After that, the mice were treated with Luteolin for two weeks at a dose of 80 mg/kg/day. To monitor the biochemical changes, we conducted western blotting and immunofluorescence analysis. According to our findings, the infusion of amyloid-beta activated c-Jun N-terminal kinases (p-JNK), p38 mitogen-activated protein kinases, glial fibrillary acidic protein (GFAP), and ionized calcium adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental mice; these changes were significantly inhibited in Aβ<sub>1</sub>–<sub>42</sub> + Luteolin-treated mice. Likewise, we also checked the expression of inflammatory markers, such as p-nuclear factor-kB p65 (p-NF-kB p65 (Ser536), tissue necrosis factor (TNF-α), and Interleukin1-β (IL-1β), in Aβ<sub>1</sub>–<sub>42</sub>-injected mice brain, which was attenuated in Aβ<sub>1</sub>–<sub>42</sub> + Luteolin-treated mice brains. Further, we investigated the expression of pro- and anti-apoptotic cell death markers such as Bax, Bcl-2, Caspase-3, and Cox-2, which was significantly reduced in Aβ<sub>1</sub>–<sub>42</sub> + Lut-treated mice brains compared to the brains of the Aβ-injected group. The results also indicated that with the administration of Aβ<sub>1</sub>–<sub>42</sub>, the expression levels of β-site amyloid precursor protein cleaving enzyme (BACE-1) and amyloid-beta (Aβ<sub>1</sub>–<sub>42</sub>) were significantly enhanced, while they were reduced in Aβ<sub>1</sub>–<sub>42</sub> + Luteolin-treated mice. We also checked the expression of synaptic markers such as PSD-95 and SNAP-25, which was significantly enhanced in Aβ<sub>1</sub>–<sub>42</sub> + Lut-treated mice. To unveil the underlying factors responsible for the protective effects of Luteolin against AD, we used a specific JNK inhibitor, which suggested that Luteolin reduced Aβ-associated neuroinflammation and neurodegeneration via inhibition of JNK. Collectively, our results indicate that Luteolin could serve as a novel therapeutic agent against AD-like pathological changes in mice.https://www.mdpi.com/1422-0067/22/17/9583amyloid-betaAlzheimer’s diseaseluteolinneurodegenerationneuroprotection |
| spellingShingle | Sareer Ahmad Myeung Hoon Jo Muhammad Ikram Amjad Khan Myeong Ok Kim Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s Disease International Journal of Molecular Sciences amyloid-beta Alzheimer’s disease luteolin neurodegeneration neuroprotection |
| title | Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s Disease |
| title_full | Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s Disease |
| title_fullStr | Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s Disease |
| title_full_unstemmed | Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s Disease |
| title_short | Deciphering the Potential Neuroprotective Effects of Luteolin against Aβ<sub>1</sub>–<sub>42</sub>-Induced Alzheimer’s Disease |
| title_sort | deciphering the potential neuroprotective effects of luteolin against aβ sub 1 sub sub 42 sub induced alzheimer s disease |
| topic | amyloid-beta Alzheimer’s disease luteolin neurodegeneration neuroprotection |
| url | https://www.mdpi.com/1422-0067/22/17/9583 |
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