Apigenin Regulates Activation of Microglia and Counteracts Retinal Degeneration

Chumsakul, Onuma; Wakayama, Kanaho; Tsuhako, Asano; Baba, Yoshihiko; Takai, Yoshihiro; Kurose, Takahiro; Honma, Yoichi; Watanabe, Sumiko

doi:10.1089/jop.2019.0163

Cited by 16 publications

(12 citation statements)

References 38 publications

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“…Flavonoids represent a minor phytochemical class of C . sativa components, but compounds such as apigenin and luteolin, which have a clear anti‐inflammatory profile, occur in the phytocomplex of the species (Borgonetti et al, 2019; Che et al, 2020; Chumsakul et al, 2020; Kao et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Other minor phytocannabinoids, such as cannabigerol (CBG) and its derivates, have shown promising neuroprotective potential in neurodegenerative diseases (García et al, 2018;Stone, Murphy, England, & O'Sullivan, 2020). Flavonoids represent a minor phytochemical class of C. sativa components, but compounds such as apigenin and luteolin, which have a clear anti-inflammatory profile, occur in the phytocomplex of the species (Borgonetti et al, 2019;Che et al, 2020;Chumsakul et al, 2020;Kao et al, 2011).…”

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confidence: 99%

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Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors‐, endocannabinoids‐, and NF‐κB‐mediated signaling

Borgonetti

Benatti

Governa

et al. 2022

Phytotherapy Research

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Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD‐ and terpenes‐enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV‐2 microglial cells, compared with CBD and β‐caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS‐induced upregulation of the pro‐inflammatory cytokines IL‐1β, IL‐6, and TNF‐α was significantly attenuated by CSE and only partially by CBD, whereas CAR was ineffective. In BV‐2 cells, these anti‐inflammatory effects exerted by CSE phytocomplex were only partially dependent on CB2r modulation and they were mediated by the regulation of enzymes responsible for the endocannabinoids metabolism, by the inhibition of reactive oxygen species release and the modulation of JNK/p38 cascade with consequent NF‐κB p65 nuclear translocation suppression. Our data suggest that C. sativa phytocomplex and its multitarget mechanism could represent a novel therapeutic strategy for neuroinflammatory‐related diseases.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors‐, endocannabinoids‐, and NF‐κB‐mediated signaling

Borgonetti

Benatti

Governa

et al. 2022

Phytotherapy Research

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“…Resveratrol could promote the M2 type transformation of microglia by inhibiting the expression of miR-155, thus improving the neuroinflammation after cerebral ischemia [35]. Apigenin reduced the number of M1 type microglia by inhibiting the expression of miR-155 but does not promote the increase of M2 type microglia, in treating retinal degeneration [36]. In this study, we found that APS inhibited the Oxidative Medicine and Cellular Longevity M1 type and obviously canceled the promotion effect of APS on M2 type, which suggested that the regulation of M1/M2 polarization phenotype balance by APS may be mediated by miR-155.…”

Section: Discussionmentioning

confidence: 99%

Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR‐155 in Experimental Autoimmune Encephalomyelitis

Liu

Ding

et al. 2021

Oxidative Medicine and Cellular Longevity

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Activated microglia is considered to be major mediators of the neuroinflammatory environment in demyelinating diseases of the central nervous system (CNS). Activated microglia are mainly polarized into M1 type, which plays a role in promoting inflammation and demyelinating. However, the proportion of microglia polarized into M2 type is relatively low, which cannot fully play the role of anti-inflammatory and resistance to demyelinating. Our previous study found that Astragalus polysaccharides (APS) has an immunomodulatory effect and can inhibit neuroinflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), which is a classic animal model of CNS demyelinating disease. In this study, we found that APS was effective in treating EAE mice. It restored microglia balance by inhibiting the polarization of microglia to M1-like phenotype and promoting the polarization of microglia to M2-like phenotype in vivo and in vitro. miR-155 is a key factor in regulating microglia polarization. We found that APS could inhibit the expression level of miR-155 in vivo and in vitro. Furthermore, we performed transfection overexpression and blocking experiments. The results showed that miR-155 mediated the polarization of microglia M1/M2 phenotype, while the selective inhibitor of miR-155 attenuated the inhibition of APS on microglia M1 phenotype and eliminated the promotion of APS on microglia M2 phenotype. Microglia can secrete IL-1α, TNF-α, and C1q after polarizing into M1 type and induce the activation of A1 neurotoxic astrocytes, further aggravating neuroinflammation and demyelination. APS reduced the secretion of IL-1α, TNF-α, and C1q by activated microglia, thus inhibited the formation of A1 neurotoxic astrocytes. In summary, our study suggests that APS regulates the polarization of microglia from M1 to M2 phenotype by inhibiting the miR-155, reduces the secretion of inflammatory factors, and inhibits the activation of neurotoxic astrocytes, thus effectively treating EAE.

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“…Furthermore, this result is consistent with the UPLC-Ms/Ms analysis, which substantially confirmed the presence of several phenolic compounds ( Table 5 ). Interestingly, previously published papers demonstrated an anti-candidal, anti-biofilm, anti-hyphal forming, and cytoprotective effect on retinal cells of some of the UPLC-detected molecules, including acteoside [ 37 , 38 , 39 , 40 , 41 , 42 ], apigenin [ 43 , 44 , 45 , 46 , 47 , 48 , 49 ], luteolin [ 46 , 50 , 51 , 52 , 53 , 54 ], and salidroside [ 55 , 56 , 57 , 58 ]. Since all these biological activities reflect the obtained results, it is possible to hypothesize that the antifungal and re-epithelizing effects of OCLE could be mediated by these chemical agents.…”

Section: Discussionmentioning

confidence: 99%

Anti-Candidal Activity of the Parasitic Plant Orobanche crenata Forssk

et al. 2021

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Candida albicans (C. albicans) and Candida glabrata (C. glabrata) are part of the human microbiome. However, they possess numerous virulence factors, which confer them the ability to cause both local and systemic infections. Candidiasis can involve multiple organs, including the eye. In the present study, we investigated the anti-candidal activity and the re-epithelizing effect of Orobanche crenata leaf extract (OCLE). By the microdilution method, we demonstrated an inhibitory effect of OCLE on both C. albicans and C. glabrata growth. By crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of OCLE to inhibit the biofilm formation and the viability of yeast cells, respectively. By germ tube and adhesion assays, we proved the capacity of OCLE to affect the morphological transition of C. albicans and the adhesion of both pathogens to human retinal pigment epithelial cells (ARPE-19), respectively. Besides, by MTT and wound healing assay, we evaluated the cytotoxic and re-epithelizing effects of OCLE on ARPE-19. Finally, the Folin–Ciocalteu and the ultra-performance liquid chromatography-tandem mass spectrometry revealed a high content of phenols and the presence of several bioactive molecules in the extract. Our results highlighted new properties of O. crenata, useful in the control of Candida infections.

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Apigenin Regulates Activation of Microglia and Counteracts Retinal Degeneration

Cited by 16 publications

References 38 publications

Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors‐, endocannabinoids‐, and NF‐κB‐mediated signaling

Non‐psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors‐, endocannabinoids‐, and NF‐κB‐mediated signaling

Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR‐155 in Experimental Autoimmune Encephalomyelitis

Anti-Candidal Activity of the Parasitic Plant Orobanche crenata Forssk

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