Esculetin attenuates lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice

Zhu, Lingpeng; Nang, Chen; Luo, Fen; Pan, Hong; Zhang, Kai; Liu, Jingyan; Zhou, Rui; Gao, Jin; Chang, Xiayun; He, He; Qiu, Yue; Wang, Jinglei; Long, Hongyan; Liu, Yu; Yan, Tianhua

doi:10.1016/j.physbeh.2016.04.051

Cited by 75 publications

(36 citation statements)

References 35 publications

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“…Because of a low volume of sample tissues, the hippocampal TNFα content was not determined in the present study however, presence of a significant difference in the serum TNFα might be considered as an evidence for effectiveness of LPS in a dose which was used in the present study. Consistently, LPS has been able to significantly increase hippocampal concentration of TNFα when was used even in a lower dose from the dose which was used in the present study [43,44].…”

Section: Discussionsupporting

confidence: 78%

Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat

et al. 2016

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Section: Discussionsupporting

confidence: 78%

Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat

et al. 2016

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“…Esculetin, 6, 7-dihydroxycoumarin, is an active ingredient originally isolated from the bark of some natural plants, including Fraxinus rhynchophylla Hance, Fraxinus chinensis Roxb, and Fraxinus aboana Lingelsh ( 14 , 15 ). It has been shown that esculetin has some biological and pharmacological activities, including anti-oxidative ( 16 , 17 ), anti-inflammatory ( 18 ), anti-viral ( 19 ), anti-asthmatic ( 20 ), and anti-tumor effects ( 21 , 22 ). As an anti-inflammatory drug, esculetin can exert therapeutic effects on several inflammatory diseases, such as hepatic fibrosis ( 23 ), arthritis ( 24 ), and atopic dermatitis ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

Esculetin Ameliorates Psoriasis-Like Skin Disease in Mice by Inducing CD4+Foxp3+ Regulatory T Cells

et al. 2018

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Psoriasis is an autoimmune and inflammatory skin disease affecting around 2–3% of the world's population. Patients with psoriasis need extensive treatments with global immunosuppressive agents that may cause severe side effects. Esculetin, a type of coumarins, is an active ingredient extracted mainly from the bark of Fraxinus rhynchophylla, which has been used to treat inflammatory and autoimmune diseases in China. However, the antipsoriatic effects of esculetin have not been reported. In this study, we aimed to investigate the effects of esculetin on psoriatic skin inflammation in a mouse model and explored the potential molecular mechanisms underlying its action. We found that esculetin ameliorated the skin lesion and reduced PASI scores as well as weight loss in imiquimod-induced psoriasis-like mice, accompanied with weakened proliferation and differentiation of keratinocytes and T cell infiltration in esculetin-treated psoriatic mice. In addition, esculetin reduced the frequency of CD8+CD44highCD62Llow effector T cells in psoriatic mice. In contrast, it increased the frequency of CD4+Foxp3+ Tregs in both lymph nodes and spleens of the psoriatic mice while promoting the differentiation of CD4+CD25− T cells into CD4+Foxp3+ Tregs in vitro. Interestingly, depleting CD4+Foxp3+ Tregs largely reversed esculetin-mediated reduction in PASI scores, indicating that esculetin attenuates murine psoriasis mainly by inducing CD4+Foxp3+ Tregs. Furthermore, the mRNA levels of proinflammatory cytokines in the psoriatic mouse skin, including IL-6, IL-17A, IL-22, IL-23, TNF-α, and IFN-γ, were dramatically decreased by the treatment with esculetin. Finally, we found that esculetin inhibited the phosphorylation of IKKα and P65 in the psoriatic skin, suggesting that it inhibits the activation of NF-κB signaling. Thus, we have demonstrated that esculetin attenuates psoriasis-like skin lesion in mice and may be a potential therapeutic candidate for the treatment of psoriasis in clinic.

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“…This compound is found in many plants, such as Artemisia capillaris, Ceratostigma willmottianum and Citrus limonia that have been used in traditional Oriental herbal medicine for many decades (22,23). Esculetin has been reported to have diverse pharmacological actions, including anti-neurotoxicity (24,25), anti-angiogenesis (26), anti-inflammatory (27,28), and antitumor activities (29)(30)(31)(32). More recently, esculetin has been shown to have beneficial effects on cellular oxidative stress (33)(34)(35).…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective effects of esculetin against oxidative stress are associated with the upregulation of Nrf2-mediated NQO1 expression via the activation of the ERK pathway

Han

Park

Lee

et al. 2016

International Journal of Molecular Medicine

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Esculetin, a coumarin derivative isolated from a variety of medicinal herbs, has been reported to possess multiple therapeutic and pharmacological actions. Although several studies have demonstrated the antioxidant activity of esculetin, its mechanisms of action have not been clearly established. The aim of this study was to evaluate the effects of esculetin against hydrogen peroxide (H2O2)‑induced oxidative stress in C2C12 myoblasts and to investigate the mechanisms involved in this process. Our data indicated that esculetin preconditioning significantly attenuated H2O2‑induced growth inhibition and DNA damage and the apoptosis of C2C12 cells by suppressing intracellular reactive oxygen species (ROS) accumulation. Treatment with esculetin effectively increased the phosphorylation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1). Esculetin treatment also activated extracellular signal‑regulated kinase (ERK), and pre‑treatment with PD98059, an ERK‑specific inhibitor, blocked esculetin-mediated phosphorylation of Nrf2 and the induction of NQO1 expression. In addition, the protective effects of esculetin against H2O2‑induced ROS accumulation, apoptosis and growth inhibition were abrogated in the C2C12 cells pre‑treated with PD98059. Thus, the present study demonstrates that esculetin protects C2C12 cells against oxidative stress-induced injury, possibly through the activation of the Nrf2/NQO1 pathway.

show abstract

Esculetin attenuates lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice

Cited by 75 publications

References 35 publications

Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat

Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat

Esculetin Ameliorates Psoriasis-Like Skin Disease in Mice by Inducing CD4+Foxp3+ Regulatory T Cells

Cytoprotective effects of esculetin against oxidative stress are associated with the upregulation of Nrf2-mediated NQO1 expression via the activation of the ERK pathway

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