Aesculetin exhibited anti-inflammatory activities through inhibiting NF-кB and MAPKs pathway in vitro and in vivo

Wang, Shou-Kai; Chen, Ting-Xiao; Wang, Wei; Xu, Ling Ling; Zhang, Yuqing; Jin, Zhen; Liu, You-Bin; Tang, You‐Zhi

doi:10.1016/j.jep.2022.115489

Cited by 24 publications

(15 citation statements)

References 43 publications

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“…In addition, a recent study indicated that esculetin was also able to inhibit the activation of NLR family pyrin domain containing 3 inflammasome in LPSinduced RAW264.7 cells. [78] Other in vivo experiments have similarly confirmed the anti-inflammatory activity of esculetin. In LPS-induced mice with acute lung injury, pretreatment with esculetin (20 and 40 mg/kg) significantly attenuated LPS-induced histopathologic changes, decreased inflammatory cell infiltration, and reduced the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in lung tissue.…”

Section: Anti-inflammatory Activity Of Esculetinmentioning

confidence: 81%

Pharmacological activities of esculin and esculetin: A review

Cai,

Cai

2023

Medicine

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Esculin and esculetin are 2 widely studied coumarin components of Cortex Fraxini, which is a well-known herbal medicine with a 2000-year history. In vivo and in vitro studies have demonstrated that both have a variety of pharmacological activities, including antioxidant, anti-tumor, anti-inflammatory, antibacterial, antidiabetic, immunomodulatory, anti-atherosclerotic, and so on. Their underlying mechanisms of action and biological activities include scavenging free radicals, modulating the nuclear factor erythroid 2-related factor 2 pathway, regulating the cell cycle, inhibiting tumor cell proliferation and migration, promoting mitochondrial pathway apoptosis, inhibiting the NF-κB and MAPK signaling pathways, regulating CD4+ T cells differentiation and associated cytokine release, inhibiting vascular smooth muscle cells, etc. This review aims to provide comprehensive information on pharmacological studies of esculin and esculetin, which is of noteworthy importance in exploring the therapeutic potential of both coumarin compounds.

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Section: Anti-inflammatory Activity Of Esculetinmentioning

confidence: 81%

Pharmacological activities of esculin and esculetin: A review

Cai,

Cai

2023

Medicine

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“…Wang et al [ 85 ] considered aesculetin, a coumarin derivative extracted from the bark of Fraxinus rhynchopylla , to investigate its effects in activating the NF-kB pathway and MAPKs in vivo and in vitro model of colitis. In vitro, before treatment, there was an increase in NO, iNOS expression, p–NF–κB-P65 expression, NF-kB P65 nuclear translocation, p38 phosphorylation, JNK phosphorylation, ERK phosphorylation, and NLRP3 expression.…”

Section: Discussionmentioning

confidence: 99%

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

et al. 2023

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Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn’s disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-κB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-KB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

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“…In the same experimental model of intestinal inflammation using C57BL/6 female mice, esculetin orally administered at 20 mg/Kg ameliorated intestinal injury, decreased MPO activity and IL-6 and TNF-α production, and inhibited NF-κB/MPAKs signaling pathways [82]. The inhibitory action of the NF-κB activation, p38, JNK, and extracellular signal-regulated kinase (ERK) phosphorylation, and IL-6, nitric oxide (NO), and TNF-α production were corroborated in RAW264.7 cells treated with 10, 25 and 50 µM of esculetin [82].…”

Section: Esculetin 4-methylesculetin and Esculinmentioning

confidence: 94%

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

Stasi

2023

Pharmaceuticals

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Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor related to stress response and cellular homeostasis that plays a key role in maintaining the redox system. The imbalance of the redox system is a triggering factor for the initiation and progression of non-communicable diseases (NCDs), including Inflammatory Bowel Disease (IBD). Nrf2 and its inhibitor Kelch-like ECH-associated protein 1 (Keap1) are the main regulators of oxidative stress and their activation has been recognized as a promising strategy for the treatment or prevention of several acute and chronic diseases. Moreover, activation of Nrf2/keap signaling pathway promotes inhibition of NF-κB, a transcriptional factor related to pro-inflammatory cytokines expression, synchronically promoting an anti-inflammatory response. Several natural coumarins have been reported as potent antioxidant and intestinal anti-inflammatory compounds, acting by different mechanisms, mainly as a modulator of Nrf2/keap signaling pathway. Based on in vivo and in vitro studies, this review focuses on the natural coumarins obtained from both plant products and fermentative processes of food plants by gut microbiota, which activate Nrf2/keap signaling pathway and produce intestinal anti-inflammatory activity. Although gut metabolites urolithin A and urolithin B as well as other plant-derived coumarins display intestinal anti-inflammatory activity modulating Nrf2 signaling pathway, in vitro and in vivo studies are necessary for better pharmacological characterization and evaluation of their potential as lead compounds. Esculetin, 4-methylesculetin, daphnetin, osthole, and imperatorin are the most promising coumarin derivatives as lead compounds for the design and synthesis of Nrf2 activators with intestinal anti-inflammatory activity. However, further structure–activity relationships studies with coumarin derivatives in experimental models of intestinal inflammation and subsequent clinical trials in health and disease volunteers are essential to determine the efficacy and safety in IBD patients.

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Aesculetin exhibited anti-inflammatory activities through inhibiting NF-кB and MAPKs pathway in vitro and in vivo

Cited by 24 publications

References 43 publications

Pharmacological activities of esculin and esculetin: A review

Pharmacological activities of esculin and esculetin: A review

Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

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