The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity

Silva, Alessandra Bispo da; Coelho, Paulo Lucas Cerqueira; Oliveira, Mona das Neves; Oliveira, Joana L.; Amparo, Jéssika Alves Oliveira; Silva, Karina Costa da; Soares, Janaina Ribeiro Pereira; Pitanga, Bruno Penas Seara; Souza, Catiane; Lopes, Giselle Pinto de Faria; Silva, Víctor Diógenes Amaral da; Costa, Maria de Fátima Dias; Junier, Marie Pierre; Chneiweiss, Hervé; Moura‐Neto, Vivaldo; Costa, Sílvia Lima

doi:10.1016/j.bbi.2019.05.003

Cited by 74 publications

(58 citation statements)

References 41 publications

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“…In order to verify the antimigratory capacity of the flavonoid apigenin, we performed an assay with the microglia‐conditioned medium treated with this flavonoid. When glioma cells were submitted to treatment with the microglia‐conditioned medium under control conditions, we observed a migratory effect of C6 glioma cells, indicating an influence of soluble factors released by microglia that favor tumor invasion, similar effects observed in the same models of study with the flavonoids rutin and quercetin (da Silva et al, ). However, when the microglia were treated with apigenin (50 μM), glioma migration was inhibited.…”

Section: Discussionsupporting

confidence: 77%

“…In a similar study, Mukherjee et al () used flavonoids to treated mice with glioblastoma cells and repolarized M2‐ like tumor associated with microglia cells to the tumoricidal M1 phenotype and intra glioblastoma recruitment of natural killer cells. Quantitative analysis of chemotaxis assays showed a significant and dose‐dependent increase in microglial migration towards C6 cultures treated with apigenin compared with the controls, indicating the property of apigenin to recruit microglia cells with M1 profile to the tumor area and similar results observed with flavonoids rutin and quercetin (da Silva et al, ).…”

Section: Discussionmentioning

confidence: 59%

“…Cardenas, Marder, Blank, and Roguin (2006) reported in their in vitro research that the flavonoid apigenin inhibited the proliferation and viability of breast cancer, melanoma, uterine cervix, and adenocarcinoma cells. Previous studies, with the use of apigenin and others flavonoids, have demonstrated the antiproliferative and apoptotic effects on glioblastoma cells (Stump et al, 2017) and antitumoral and immunomodulatory potential in C6 glioma cell line, in terms of cytotoxicity, inhibition of migration, and regulation of trophic factors that reduced tumor growth and migration with similar results in co-cultures microglia/glioma cells (Coelho et al, 2016;da Silva et al, 2019). Other studies have also showed that apigenin is able to inhibit glioblastoma cell proliferation, induce its differentiation and apoptosis (Coelho et al, 2015;Stump et al, 2017), and decrease the expression of pro-angiogenic factors like VEGF and TGFβ-1 (Freitas et al, 2010) and inhibits glioblastoma stem cells (Kim, Jung, Lee, Sohng, & Jung, 2016).…”

Section: Figurementioning

confidence: 70%

“…Flavonoids are polyphenolic compounds that have several biological properties, among which are anti‐inflammatory, antioxidant, and antitumor (Ielpo et al, ). Their ability of flavonoids, to inhibit the proliferation of glioma cells, has been reported in many studies (da Silva et al, ; Maués et al, ; Santos et al, ), without toxicity in brain normal cells (Coelho et al, ; Das, Banik, & Ray, ). Also, as recently demonstrated by da Silva et al () flavonoids can modulate the microglia inflammatory profile that impacts on their antiglioma properties.…”

Section: Introductionmentioning

confidence: 89%

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Apigenin from Croton betulaster Müll restores the immune profile of microglia against glioma cells

Coelho

Amparo

Silva

et al. 2019

Phytotherapy Research

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The flavonoid apigenin, extracted from the Brazilian plant Croton betulaster Müll. has demonstrated the ability to inhibit proliferation, induce differentiation, and modify the inflammatory profile of glioma cells. The aim of the present study was to evaluate the effect of apigenin on chemotaxis and regulation of inflammatory cytokines of microglia cells and these impacts on glioma cell growth. In cultures of isolated rat microglia, it was observed that apigenin induced changes in Iba1‐positive cells to an ameboid phenotype, associated to an increase in the expression of the activated M1 profile marker OX‐42 and iNOS and a reduction in the expression of the M2 profile marker CD206. Besides, apigenin modulated the tumor necrosis factor and IL‐10 release by microglia. Treatment of C6 glioma cells with conditioned medium of microglia treated with apigenin‐induced reduction of tumor migration and viability, associated with significant reduction in IL‐6 levels. On the other hand, treatment of C6 cells with apigenin‐induced microglia chemotaxis to glioma in vitro. Moreover, apigenin treatment of microglia/C6 co‐cultures induced preferentially reduction in the viability of C6 cells and increased microglia‐activated phenotype, associated with a change in the balance of TNF/IL‐10 levels. Together, these results demonstrated that the flavonoid apigenin restores the immune profile of microglia against glioma cells.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 59%

Section: Figurementioning

confidence: 70%

Section: Introductionmentioning

confidence: 89%

See 2 more Smart Citations

Apigenin from Croton betulaster Müll restores the immune profile of microglia against glioma cells

Coelho

Amparo

Silva

et al. 2019

Phytotherapy Research

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show abstract

“…10g, P > 0.05). Data represented mean ± SEM, n = 3 per group, *P < 0.05, **P < 0.01, ***P < 0.001. quercetin to modulate inflammation in the microglia and inhibit the proliferation of gliomas (da Silva et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

Liu

Gao

et al. 2020

Brain, Behavior, and Immunity

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CpG and Rutin Co‐Loaded DNA Tetrahedra for Targeted Therapy of Intracerebral Hemorrhage: Synergistic Hematoma Clearance and Neuroinflammation Inhibition

Wang,

Xie,

et al. 2024

Adv Funct Materials

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Intracerebral hemorrhage (ICH) presents a formidable challenge due to its high mortality and disability rates, primarily attributed to cerebral hematoma formation and ensuing neuroinflammation. Swift hematoma removal is paramount for prognosis, yet existing interventions carry risks and limitations. Notably, elevated CD47 expression on hematoma‐associated RBC triggers a “don't eat me” signal, impeding hematoma clearance, while microglial/macrophage erythrophagocytosis exacerbates oxidative stress and the RBC lysate evokes neuroinflammation. To address this conundrum, a multifunctional nanomedicine (TD‐CFR), employing DNA tetrahedra (TD) as a carrier for ICH treatment is introduced. The investigations reveal that CpG enhances the phagocytosis of CD47‐expressing RBC by microglia/macrophages via lipid metabolism modulation. Integration of CpG into TD preserves its pro‐phagocytic efficacy, while TD's double‐stranded region enables efficient encapsulation of Rutin, a potent anti‐inflammatory and antioxidant flavonoid. Capitalizing on disrupted blood‐brain barrier integrity at the hemorrhage site, TD‐CFR achieves robust enrichment within cerebral hematoma post‐intravenous administration, augmented by folate receptor‐mediated targeting of microglia/macrophages. Efficacy assessments in mouse and rabbit ICH models confirm TD‐CFR's therapeutic benefits, including hematoma clearance, neuroinflammation suppression, and brain function restoration. Leveraging TD's high biosafety profile and dual active ingredient loading capacity, the study unveils a promising drug treatment paradigm for ICH.

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The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity

Cited by 74 publications

References 41 publications

Apigenin from Croton betulaster Müll restores the immune profile of microglia against glioma cells

Apigenin from Croton betulaster Müll restores the immune profile of microglia against glioma cells

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

CpG and Rutin Co‐Loaded DNA Tetrahedra for Targeted Therapy of Intracerebral Hemorrhage: Synergistic Hematoma Clearance and Neuroinflammation Inhibition

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