Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

Rzodkiewicz, Przemysław; Gąsińska, Emilia; Gajewski, Michał; Bujalska‐Zadrożny, Magdalena; Szukiewicz, Dariusz; Maśliński, S

doi:10.5114/reum.2016.62469

Cited by 19 publications

(14 citation statements)

References 19 publications

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“…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 ). Previous studies have also reported that esculetin inhibits T cell activation without suppressing IL-2 production or IL-2 receptor expression ( 26 ).…”

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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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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“…Similarly, esculetin at 100 µM significantly inhibits proteoglycan depletion, pro-MMP1, pro-MMP3, and MMP production in rabbit chondrocytes [ 96 ]. Esculetin at 10 mg/kg dose effectively reduces the level of leukotriene B4 in the plasma of rats with adjuvant-induced arthritis (AIA) [ 97 ].…”

Section: Therapeutic Applications Of Esculetinmentioning

confidence: 99%

Pharmacological and Therapeutic Applications of Esculetin

Garg

Gupta

Sahu

et al. 2022

IJMS

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Esculetin is a coumarin compound, which belongs to the class of benzopyrone enriched in various plants such as Sonchus grandifolius, Aesculus turbinata, etc. Free radicals lead to the development of oxidative stress causing inflammation, arthritis, cancer, diabetes, fatty liver disease, etc. These further reduce the efficacy of anticancer drugs, activate inflammatory signaling pathways, degrade joints and cartilage, and disrupt the glycemic index and normal function of liver enzymes. For instance, the current treatment modalities used in arthritis such as non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatoid drugs, and lipoxygenase inhibitors present limited efficacy and adverse effects. Thus, there is a constant need to find newer and safer alternatives. Esculetin has an immense antioxidative potential thereby alleviating arthritis, diabetes, malignancies, and hepatic disorders. Structurally, esculetin contains two hydroxyl groups, which enhance its ability to function as an antioxidant by inhibiting oxidative stress in pathological conditions. Leukotriene B4 synthesis, NF-κB and MPAK pathway activation, and inflammatory cytokine production are the main causes of bone and joint deterioration in arthritis, whereas esculetin treatment reverses these factors and relieves the disease condition. In contrast, lipid peroxidation caused by upregulation of TGF-β-mediated expression and dysfunction of antioxidant enzymes is inhibited by esculetin therapy, thus reducing liver fibrosis by acting on the PI3K/FoxO1 pathway. Therefore, targeting NF-κB, pro-inflammatory cytokines, TGF-β and oxidative stress may be a therapeutic strategy to alleviate arthritis and liver fibrosis.

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“…A broad range of inflammatory or oxidative conditions have been shown to be impacted by esculetin. These include lung injury and fibrosis ( 356 , 357 , 520 ); fibromyalgia ( 521 ); neuronal oxidative stress ( 522 ); psoriasis ( 523 ); arthritis ( 358 ); nociception ( 359 ); colitis ( 360 ); allergy, immunity, and asthma ( 282 , 354 , 380 – 383 ); and sepsis ( 361 ). The effects of esculetin on numerous cancer cell types have been extensively studied ( 94 , 321 – 342 , 519 , 524 , 525 ) and are the basis for efforts to develop novel therapeutics ( 98 , 341 ).…”

Section: Effects Of Bioactive Compounds Found In a Scopariamentioning

confidence: 99%

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

et al. 2022

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Botanicals have a long history of medicinal use for a multitude of ailments, and many modern pharmaceuticals were originally isolated from plants or derived from phytochemicals. Among these, artemisinin, first isolated from Artemisia annua, is the foundation for standard anti-malarial therapies. Plants of the genus Artemisia are among the most common herbal remedies across Asia and Central Europe. The species Artemisia scoparia (SCOPA) is widely used in traditional folk medicine for various liver diseases and inflammatory conditions, as well as for infections, fever, pain, cancer, and diabetes. Modern in vivo and in vitro studies have now investigated SCOPA’s effects on these pathologies and its ability to mitigate hepatotoxicity, oxidative stress, obesity, diabetes, and other disease states. This review focuses on the effects of SCOPA that are particularly relevant to metabolic health. Indeed, in recent years, an ethanolic extract of SCOPA has been shown to enhance differentiation of cultured adipocytes and to share some properties of thiazolidinediones (TZDs), a class of insulin-sensitizing agonists of the adipogenic transcription factor PPARγ. In a mouse model of diet-induced obesity, SCOPA diet supplementation lowered fasting insulin and glucose levels, while inducing metabolically favorable changes in adipose tissue and liver. These observations are consistent with many lines of evidence from various tissues and cell types known to contribute to metabolic homeostasis, including immune cells, hepatocytes, and pancreatic beta-cells. Compounds belonging to several classes of phytochemicals have been implicated in these effects, and we provide an overview of these bioactives. The ongoing global epidemics of obesity and metabolic disease clearly require novel therapeutic approaches. While the mechanisms involved in SCOPA’s effects on metabolic, anti-inflammatory, and oxidative stress pathways are not fully characterized, current data support further investigation of this plant and its bioactives as potential therapeutic agents in obesity-related metabolic dysfunction and many other conditions.

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Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

Cited by 19 publications

References 19 publications

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

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

Pharmacological and Therapeutic Applications of Esculetin

Artemisia scoparia and Metabolic Health: Untapped Potential of an Ancient Remedy for Modern Use

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