The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment
Formaldehyde (FA) has been found to induce major Alzheimer’s disease (AD)-like features including cognitive impairment, Aβ deposition, and Tau hyperphosphorylation, suggesting that it may play a significant role in the initiation and progression of AD. Therefore, elucidating the mechanism underlying...
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2023-05-01
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| author | Fan Chen Na Wang Xinyan Tian Juan Su Yan Qin Rongqiao He Xiaping He |
| author_facet | Fan Chen Na Wang Xinyan Tian Juan Su Yan Qin Rongqiao He Xiaping He |
| author_sort | Fan Chen |
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| description | Formaldehyde (FA) has been found to induce major Alzheimer’s disease (AD)-like features including cognitive impairment, Aβ deposition, and Tau hyperphosphorylation, suggesting that it may play a significant role in the initiation and progression of AD. Therefore, elucidating the mechanism underlying FA-induced neurotoxicity is crucial for exploring more comprehensive approaches to delay or prevent the development of AD. Mangiferin (MGF) is a natural C-glucosyl-xanthone with promising neuroprotective effects, and is considered to have potential in the treatment of AD. The present study was designed to characterize the effects and mechanisms by which MGF protects against FA-induced neurotoxicity. The results in murine hippocampal cells (HT22) revealed that co-treatment with MGF significantly decreased FA-induced cytotoxicity and inhibited Tau hyperphosphorylation in a dose-dependent manner. It was further found that these protective effects were achieved by attenuating FA-induced endoplasmic reticulum stress (ERS), as indicated by the inhibition of the ERS markers, GRP78 and CHOP, and downstream Tau-associated kinases (GSK-3β and CaMKII) expression. In addition, MGF markedly inhibited FA-induced oxidative damage, including Ca<sup>2+</sup> overload, ROS generation, and mitochondrial dysfunction, all of which are associated with ERS. Further studies showed that the intragastric administration of 40 mg/kg/day MGF for 6 weeks significantly improved spatial learning ability and long-term memory in C57/BL6 mice with FA-induced cognitive impairment by reducing Tau hyperphosphorylation and the expression of GRP78, GSK-3β, and CaMKII in the brains. Taken together, these findings provide the first evidence that MGF exerts a significant neuroprotective effect against FA-induced damage and ameliorates mice cognitive impairment, the possible underlying mechanisms of which are expected to provide a novel basis for the treatment of AD and diseases caused by FA pollution. |
| format | Article |
| id | doaj-art-8f6d72b7edce4dda8ed4d9eb53a358ae |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2023-05-01 |
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| series | Pharmaceutics |
| spelling | doaj-art-8f6d72b7edce4dda8ed4d9eb53a358ae2025-01-30T15:18:54ZengMDPI AGPharmaceutics1999-49232023-05-01156156810.3390/pharmaceutics15061568The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive ImpairmentFan Chen0Na Wang1Xinyan Tian2Juan Su3Yan Qin4Rongqiao He5Xiaping He6School of Basic Medical Sciences, Dali University, Dali 671003, ChinaSchool of Basic Medical Sciences, Dali University, Dali 671003, ChinaSchool of Basic Medical Sciences, Dali University, Dali 671003, ChinaSchool of Basic Medical Sciences, Dali University, Dali 671003, ChinaSchool of Basic Medical Sciences, Dali University, Dali 671003, ChinaState Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100045, ChinaSchool of Basic Medical Sciences, Dali University, Dali 671003, ChinaFormaldehyde (FA) has been found to induce major Alzheimer’s disease (AD)-like features including cognitive impairment, Aβ deposition, and Tau hyperphosphorylation, suggesting that it may play a significant role in the initiation and progression of AD. Therefore, elucidating the mechanism underlying FA-induced neurotoxicity is crucial for exploring more comprehensive approaches to delay or prevent the development of AD. Mangiferin (MGF) is a natural C-glucosyl-xanthone with promising neuroprotective effects, and is considered to have potential in the treatment of AD. The present study was designed to characterize the effects and mechanisms by which MGF protects against FA-induced neurotoxicity. The results in murine hippocampal cells (HT22) revealed that co-treatment with MGF significantly decreased FA-induced cytotoxicity and inhibited Tau hyperphosphorylation in a dose-dependent manner. It was further found that these protective effects were achieved by attenuating FA-induced endoplasmic reticulum stress (ERS), as indicated by the inhibition of the ERS markers, GRP78 and CHOP, and downstream Tau-associated kinases (GSK-3β and CaMKII) expression. In addition, MGF markedly inhibited FA-induced oxidative damage, including Ca<sup>2+</sup> overload, ROS generation, and mitochondrial dysfunction, all of which are associated with ERS. Further studies showed that the intragastric administration of 40 mg/kg/day MGF for 6 weeks significantly improved spatial learning ability and long-term memory in C57/BL6 mice with FA-induced cognitive impairment by reducing Tau hyperphosphorylation and the expression of GRP78, GSK-3β, and CaMKII in the brains. Taken together, these findings provide the first evidence that MGF exerts a significant neuroprotective effect against FA-induced damage and ameliorates mice cognitive impairment, the possible underlying mechanisms of which are expected to provide a novel basis for the treatment of AD and diseases caused by FA pollution.https://www.mdpi.com/1999-4923/15/6/1568Alzheimer’s diseaseformaldehydemangiferinTau hyperphosphorylationendoplasmic reticulum stressglycogen synthase kinase-3β |
| spellingShingle | Fan Chen Na Wang Xinyan Tian Juan Su Yan Qin Rongqiao He Xiaping He The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment Pharmaceutics Alzheimer’s disease formaldehyde mangiferin Tau hyperphosphorylation endoplasmic reticulum stress glycogen synthase kinase-3β |
| title | The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment |
| title_full | The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment |
| title_fullStr | The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment |
| title_full_unstemmed | The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment |
| title_short | The Protective Effect of Mangiferin on Formaldehyde-Induced HT22 Cell Damage and Cognitive Impairment |
| title_sort | protective effect of mangiferin on formaldehyde induced ht22 cell damage and cognitive impairment |
| topic | Alzheimer’s disease formaldehyde mangiferin Tau hyperphosphorylation endoplasmic reticulum stress glycogen synthase kinase-3β |
| url | https://www.mdpi.com/1999-4923/15/6/1568 |
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