Apigenin exhibits anti-inflammatory effects in LPS-stimulated BV2 microglia through activating GSK3β/Nrf2 signaling pathway

Chen, Pengfei; Huo, Xianhao; Liu, Wenqing; Li, Kai; Sun, Zhipeng; Tian, Jihui

doi:10.1080/08923973.2019.1688345

Cited by 39 publications

(27 citation statements)

References 25 publications

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“…Apigenin is one of the most widespread flavonoids in plants ( 58 ). Apigenin from Matricaria chamomilla suppressed LPS (UO)-induced TNF-α, IL-1β, and IL-6 production in BV2 microglia via activating GSK3β/Nrf2 signaling pathway and suppressing NFκB activation ( 59 ). Also, Gastrodin, a natural phenol from Gastrodia elata BI, mediated anti-inflammatory and anti-proliferation effects in LPS ( E coli O111:B4)-stimulated BV-2 or in primary microglia by modulating the Wnt/GSK3β/β-catenin signaling pathway ( 60 ).…”

Section: Strategies To Inhibit the Inflammatory Response By Gsk3β Inhibitionmentioning

confidence: 99%

Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites

et al. 2021

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Knowledge of glycogen synthase kinase 3β (GSK3β) activity and the molecules identified that regulate its function in infections caused by pathogenic microorganisms is crucial to understanding how the intensity of the inflammatory response can be controlled in the course of infections. In recent years many reports have described small molecular weight synthetic and natural compounds, proteins, and interference RNA with the potential to regulate the GSK3β activity and reduce the deleterious effects of the inflammatory response. Our goal in this review is to summarize the most recent advances on the role of GSK3β in the inflammatory response caused by bacteria, bacterial virulence factors (i.e. LPS and others), viruses, and parasites and how the regulation of its activity, mainly its inhibition by different type of molecules, modulates the inflammation.

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Section: Strategies To Inhibit the Inflammatory Response By Gsk3β Inhibitionmentioning

confidence: 99%

Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites

et al. 2021

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“…For example, apigenin showed stronger effects than other compounds such as NR and 78c to suppress Il6 and Nos2 in cultured microglia and Il6 in cultured astrocytes (Figure 7). Moreover apigenin decreased cytokine expression even in LPS‐injected CD38 KO mice (Figure 4h–j), suggesting that it has targets beyond CD38, which could include MAPK, Akt, JNK (Ginwala et al., 2019) or the GSK3b/Nrf2 signaling pathway (Chen et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide‐induced microglial and astrocytic neuroinflammation by increasing NAD⁺

Roboon

Hattori

Ishii

et al. 2021

Journal of Neurochemistry

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Neuroinflammation is initiated by activation of the brain's innate immune system in response to an inflammatory challenge. Insufficient control of neuroinflammation leads to enhanced or prolonged pathology in various neurological conditions including multiple sclerosis and Alzheimer's disease. Nicotinamide adenine dinucleotide (NAD + ) plays critical roles in cellular energy metabolism and calcium homeostasis. Our previous study demonstrated that deletion of CD38, which consumes NAD + , suppressed cuprizone-induced demyelination, neuroinflammation, and glial activation. However, it is still unknown whether CD38 directly affects neuroinflammation through regulating brain NAD + level. In this study, we investigated the effect of CD38 deletion and inhibition and supplementation of NAD + on lipopolysaccharide (LPS)-induced neuroinflammation in mice. Intracerebroventricular injection of LPS significantly increased CD38 expression especially in the hippocampus. Deletion of CD38 decreased LPSinduced inflammatory responses and glial activation. Pre-administration of apigenin, a flavonoid with CD38 inhibitory activity, or nicotinamide riboside (NR), an NAD + precursor, increased NAD + level, and significantly suppressed induction of cytokines and chemokines, glial activation and subsequent neurodegeneration after LPS administration. In cell culture, LPS-induced inflammatory responses were suppressed by treatment of primary astrocytes or microglia with apigenin, NAD + , NR or 78c, the latter

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“…TNF-α overproduction or dysfunction, are closely related the development of chronic inflammatory diseases such as hypertension, via activating the nuclear factor-kappa B (NF-κB) [45]. Apigenin has been demonstrated to have anti-inflammatory effects [46][47][48] which can significantly attenuate LPS-induced TNF-α, IL-1β, and IL-6 production and inhibit LPS-induced NF-κB activation [49]. However, the anti-inflammatory effect of apigenin in the PVN are seldom studied and reported.…”

Section: Discussionmentioning

confidence: 99%

Apigenin Improves Hypertension and Cardiac Hypertrophy Through Modulating NADPH Oxidase-Dependent ROS Generation and Cytokines in Hypothalamic Paraventricular Nucleus

Gao

et al. 2021

Cardiovasc Toxicol

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Apigenin, identified as 4′, 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 μg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1β (IL-1β), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN.

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Apigenin exhibits anti-inflammatory effects in LPS-stimulated BV2 microglia through activating GSK3β/Nrf2 signaling pathway

Cited by 39 publications

References 25 publications

Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites

Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites

Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide‐induced microglial and astrocytic neuroinflammation by increasing NAD⁺

Apigenin Improves Hypertension and Cardiac Hypertrophy Through Modulating NADPH Oxidase-Dependent ROS Generation and Cytokines in Hypothalamic Paraventricular Nucleus

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Apigenin exhibits anti-inflammatory effects in LPS-stimulated BV2 microglia through activating GSK3β/Nrf2 signaling pathway

Cited by 39 publications

References 25 publications

Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites

Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites

Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide‐induced microglial and astrocytic neuroinflammation by increasing NAD+

Apigenin Improves Hypertension and Cardiac Hypertrophy Through Modulating NADPH Oxidase-Dependent ROS Generation and Cytokines in Hypothalamic Paraventricular Nucleus

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Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide‐induced microglial and astrocytic neuroinflammation by increasing NAD⁺