Baicalein ameliorates ischemic brain damage through suppressing proinflammatory microglia polarization via inhibiting the TLR4/NF-κB and STAT1 pathway

Ran, Yuanyuan; Qie, Shuyan; Gao, Fuhai; Ding, Zitong; Yang, Shui-Qing; Tian, Guiqin; Liu, Zongjian; Xi, Jianing

doi:10.1016/j.brainres.2021.147626

Cited by 38 publications

(21 citation statements)

References 39 publications

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“…Baicalein, an aglycone of baicalin, is also widely studied in neuroinflammation. Baicalein inhibits microglia activation and polarization with decreasing TNF-α, iNOS, IL-1β, IL-6, CD16 and CD86 production, and enhancing Arg-1 and CD206 levels in LPS plus IFN-γ-induced BV2 cells through activating STAT1 expression and inhibiting TLR4/NF-κB pathway ( 38 ), and in ischemic penumbra from middle cerebral artery occlusion (MCAO)-induced rats through the inactivation of IκBα, JNK, ERK and p38, as well as nuclear translocation of p65 ( 38 – 40 ). In other studies, baicalein is reported to reduce IFN-γ, IL-5, and IL-12 secretion, as well as repress GFAP and Iba-1 expression in substantia nigra (SN) and midbrain from MPTP or rotenone-induced PD mice via downregulating cleaved-Caspase-1, cleaved-GSDMD, and NLRP3, as well as promoting PSD95, SYP, BDNF, p-TrkB, CREB, p-PI3k, p-Akt, and p-CaMK II expression ( 41 , 42 ).…”

Section: Effects Of Natural Flavonoids On Neuroinflammationmentioning

confidence: 99%

Beneficial effects of natural flavonoids on neuroinflammation

et al. 2022

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Neuroinflammation is the fundamental immune response against multiple factors in the central nervous system and is characterized by the production of inflammatory mediators, activated microglia and astrocytes, and the recruitment of innate and adaptive immune cells to inflammatory sites, that contributes to the pathological process of related brain diseases, such as Alzheimer’s disease, Parkinson’s disease, depression, and stroke. Flavonoids, as a species of important natural compounds, have been widely revealed to alleviate neuroinflammation by inhibiting the production of pro-inflammatory mediators, elevating the secretion of anti-inflammatory factors, and modulating the polarization of microglia and astrocyte, mainly via suppressing the activation of NLRP3 inflammasome, as well as NF-κB, MAPK, and JAK/STAT pathways, promoting Nrf2, AMPK, BDNF/CREB, Wnt/β-Catenin, PI3k/Akt signals and SIRT1-mediated HMGB1 deacetylation. This review will provide the latest and comprehensive knowledge on the therapeutic benefits and mechanisms of natural flavonoids in neuroinflammation, and the natural flavonoids might be developed into food supplements or lead compounds for neuroinflammation-associated brain disorders.

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Section: Effects Of Natural Flavonoids On Neuroinflammationmentioning

confidence: 99%

Beneficial effects of natural flavonoids on neuroinflammation

et al. 2022

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“…In models of ischemia, STVNA has been implicated in inhibition of astrogliosis [ 210 ], modulation of microglia/macrophage polarization [ 211 ], and preservation of volume control in endothelial cells [ 212 ]. Flavonoids constitute a class of natural products with a significant role in the inhibition of microglial polarization and management of oxidative stress, with a number of compounds acting upon the NF-κB signaling pathway [ 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 ]. A number of the flavonoids have been implicated in the activity of stem cells, including hesperetin in NSC proliferation [ 221 ], icariin in neurogenesis and angiogenesis through release of BDNF and VEGF [ 222 ], and quercetin in enhancing stem cell viability and proliferation while reducing apoptosis [ 223 ].…”

Section: Current Nrf2-directed Treatment Modalitiesmentioning

confidence: 99%

The Role of Concomitant Nrf2 Targeting and Stem Cell Therapy in Cerebrovascular Disease

et al. 2022

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Despite the reality that a death from cerebrovascular accident occurs every 3.5 min in the United States, there are few therapeutic options which are typically limited to a narrow window of opportunity in time for damage mitigation and recovery. Novel therapies have targeted pathological processes secondary to the initial insult, such as oxidative damage and peripheral inflammation. One of the greatest challenges to therapy is the frequently permanent damage within the CNS, attributed to a lack of sufficient neurogenesis. Thus, recent use of cell-based therapies for stroke have shown promising results. Unfortunately, stroke-induced inflammatory and oxidative damage limit the therapeutic potential of these stem cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been implicated in endogenous antioxidant and anti-inflammatory activity, thus presenting an attractive target for novel therapeutics to enhance stem cell therapy and promote neurogenesis. This review assesses the current literature on the concomitant use of stem cell therapy and Nrf2 targeting via pharmaceutical and natural agents, highlighting the need to elucidate both upstream and downstream pathways in optimizing Nrf2 treatments in the setting of cerebrovascular disease.

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“…Baicalein and baicalin, and extracts containing them, are proposed for various pharmacological effects, such as anti-inflammatory, antiviral, antibacterial, anticancer, antineurodegenerative and protective, against cardiovascular diseases [ 65 , 68 , 69 ]. The molecular mechanisms of action of baicalein, as well as those of other flavonoids, are mainly linked to the antioxidant activity, which occurs in different steps of the oxidative process; for example, it has demonstrated a role as scavengers of free radicals already formed in the medium (including lipid peroxyl radicals), as chelators of metal ions and by removing oxidatively altered biomolecules [ 70 , 71 ].…”

Section: Specific Polyphenolic Compounds Of Interestmentioning

confidence: 99%

Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety

Froldi

Ragazzi

2022

Molecules

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Vascular diseases, such as peripheral artery disease (PAD), are associated with diabetes mellitus and a higher risk of cardiovascular disease and even death. Surgical revascularization and pharmacological treatments (mainly antiplatelet, lipid-lowering drugs, and antidiabetic agents) have some effectiveness, but the response and efficacy of therapy are overly dependent on the patient’s conditions. Thus, the demand for new cures exists. In this regard, new studies on natural polyphenols that act on key points involved in the pathogenesis of vascular diseases and, thus, on PAD are of great urgency. The purpose of this review is to take into account the mechanisms that lead to endothelium dysfunction, such as the glycoxidation process and the production of advanced glycation end-products (AGEs) that result in protein misfolding, and to suggest plant-derived polyphenols that could be useful in PAD. Thus, five polyphenols are considered, baicalein, curcumin, mangiferin, quercetin and resveratrol, reviewing the literature in PubMed. The key molecular mechanisms and preclinical and clinical studies of each selected compound are examined. Furthermore, the safety profiles of the polyphenols are outlined, together with the unwanted effects reported in humans, also by searching the WHO database (VigiBase).

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Baicalein ameliorates ischemic brain damage through suppressing proinflammatory microglia polarization via inhibiting the TLR4/NF-κB and STAT1 pathway

Cited by 38 publications

References 39 publications

Beneficial effects of natural flavonoids on neuroinflammation

Beneficial effects of natural flavonoids on neuroinflammation

The Role of Concomitant Nrf2 Targeting and Stem Cell Therapy in Cerebrovascular Disease

Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety

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