High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose
Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of micr...
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MDPI AG
2025-01-01
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| author | Giacomina Videtta Chiara Sasia Nicoletta Galeotti |
| author_facet | Giacomina Videtta Chiara Sasia Nicoletta Galeotti |
| author_sort | Giacomina Videtta |
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| description | Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may reduce diabetes-associated neurological comorbidities. Natural remedies containing phenolic compounds have shown efficacy in mitigating microglia-mediated neuroinflammation. The aim of this study was to investigate the potential of a <i>Melissa officinalis</i> L. (MO) phytocomplex, obtained from plant cell cultures and enriched in its main polyphenolic constituent, rosmarinic acid (RA), in attenuating hyperglycemia-induced neuroinflammation in microglia. A time-course morphological analysis of BV2 microglial cells exposed to high glucose (HG) levels showed a shift towards a proinflammatory phenotype, peaking after 48 h, which was reversed by pretreatment with MO. Biochemical assays revealed increased expression of the microglial marker CD11b (187%), activation of the NF-κB pathway (179%), expression of iNOS (225%), enhanced phosphorylation of ERK1/2 (180%), and increased expression of the proinflammatory cytokine IL-6 (173%). Pretreatment with MO prevented the aberrant expression of these proinflammatory mediators and restored SIRT1 levels. Exposure of neuronal SH-SY5Y cells to the conditioned medium from HG-exposed microglia significantly reduced cell viability. MO counteracted this effect, exhibiting neuroprotective activity. RA showed efficacy comparable to that of MO. In conclusion, MO and RA attenuated microglia-mediated oxidative imbalance and neuroinflammation under HG exposure by inhibiting the morphological shift toward a proinflammatory phenotype induced by HG and abrogating the subsequent activation of the downstream ERK1/2–NF-κB–iNOS pathway. |
| format | Article |
| id | doaj-art-66cd983ca25645a996ff284a31eb8e36 |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Antioxidants |
| spelling | doaj-art-66cd983ca25645a996ff284a31eb8e362025-08-20T02:44:29ZengMDPI AGAntioxidants2076-39212025-01-0114216110.3390/antiox14020161High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High GlucoseGiacomina Videtta0Chiara Sasia1Nicoletta Galeotti2Department of Neurosciences, Psychology, Drug Research and Child Health (Neurofarba), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, ItalyDepartment of Neurosciences, Psychology, Drug Research and Child Health (Neurofarba), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, ItalyDepartment of Neurosciences, Psychology, Drug Research and Child Health (Neurofarba), Section of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, ItalyDiabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may reduce diabetes-associated neurological comorbidities. Natural remedies containing phenolic compounds have shown efficacy in mitigating microglia-mediated neuroinflammation. The aim of this study was to investigate the potential of a <i>Melissa officinalis</i> L. (MO) phytocomplex, obtained from plant cell cultures and enriched in its main polyphenolic constituent, rosmarinic acid (RA), in attenuating hyperglycemia-induced neuroinflammation in microglia. A time-course morphological analysis of BV2 microglial cells exposed to high glucose (HG) levels showed a shift towards a proinflammatory phenotype, peaking after 48 h, which was reversed by pretreatment with MO. Biochemical assays revealed increased expression of the microglial marker CD11b (187%), activation of the NF-κB pathway (179%), expression of iNOS (225%), enhanced phosphorylation of ERK1/2 (180%), and increased expression of the proinflammatory cytokine IL-6 (173%). Pretreatment with MO prevented the aberrant expression of these proinflammatory mediators and restored SIRT1 levels. Exposure of neuronal SH-SY5Y cells to the conditioned medium from HG-exposed microglia significantly reduced cell viability. MO counteracted this effect, exhibiting neuroprotective activity. RA showed efficacy comparable to that of MO. In conclusion, MO and RA attenuated microglia-mediated oxidative imbalance and neuroinflammation under HG exposure by inhibiting the morphological shift toward a proinflammatory phenotype induced by HG and abrogating the subsequent activation of the downstream ERK1/2–NF-κB–iNOS pathway.https://www.mdpi.com/2076-3921/14/2/161neuroinflammationmicrogliadiabetes<i>Melissa officinalis</i> L.rosmarinic acid |
| spellingShingle | Giacomina Videtta Chiara Sasia Nicoletta Galeotti High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose Antioxidants neuroinflammation microglia diabetes <i>Melissa officinalis</i> L. rosmarinic acid |
| title | High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose |
| title_full | High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose |
| title_fullStr | High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose |
| title_full_unstemmed | High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose |
| title_short | High Rosmarinic Acid Content <i>Melissa officinalis</i> L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose |
| title_sort | high rosmarinic acid content i melissa officinalis i l phytocomplex modulates microglia neuroinflammation induced by high glucose |
| topic | neuroinflammation microglia diabetes <i>Melissa officinalis</i> L. rosmarinic acid |
| url | https://www.mdpi.com/2076-3921/14/2/161 |
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