HIF-prolyl hydroxylase is a potential molecular target for esculetin-mediated anti-colitic effects

Yum, Sabrina W.; Jeong, Seongkeun; Lee, Sun Young; Kim, Wooseong; Nam, Joon; Jung, Yunjin

doi:10.1016/j.fitote.2015.03.013

Cited by 18 publications

(13 citation statements)

References 26 publications

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“…sinensis against RA were analyzed using a network pharmacology approach, and five compounds, twenty-five targets, and eight pathways were finally obtained. Esculetin was shown to possess an anti-inflammatory effect by suppressing the HIF-1α signaling pathways [ 25 ]. Caffeic acid attenuated hepatocellular carcinoma cells’ angiogenesis by reducing JNK-1-mediated HIF-1α stabilization [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation

Zhao

et al. 2022

PLoS ONE

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Background Porana sinensis Hemsl. has been widely used as a substitute for Erycibes Caulis to treat rheumatoid arthritis (RA) in traditional Chinese medicine (TCM). However, little is known about the active ingredients and pharmacological mechanisms that mediate the action of P. sinensis against RA. Methods The compounds contained in P. sinensis were analyzed by Q Exactive Focus mass spectrometer. The active constituents and pharmacological mechanism of P. sinensis against RA were clarified using a network pharmacology-based investigation. LPS-induced RAW 264.7 cells was used to verify anti-inflammatory effects of the active compounds screened by network pharmacology. Collagen-induced arthritis model was used to further investigate the mechanism of P. sinensis against RA. Results The potential components and targets of P. sinensis against RA were analyzed using network pharmacology, and five compounds, twenty-five targets, and eight pathways were identified. Experimental validation suggested that P. sinensis extract and five compounds (esculetin, umbelliferone, trans-N-feruloyltyramine, caffeic acid and scopolin) could inhibit the release of inflammatory mediators (NO, TNF-α, IL-1β and IL-6) in LPS-induced RAW 264.7 cell. P. sinensis extract attenuated the severity, pathological changes, and release of cytokines (IL-6 and HIF-1α) during RA progression by regulating the PI3K/AKT and HIF-1 pathways. Conclusion The study provides a basis for the application of P. sinensis against RA. Our findings may provide suggestions for developing P. sinensis into a substitute for Erycibes Caulis.

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Section: Discussionmentioning

confidence: 99%

Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation

Zhao

et al. 2022

PLoS ONE

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“…Esculetin has been reported to inhibit the RhoA/Rho kinase pathway, followed by the downregulation of TNF-α, IL-1β, and IL-6 thereby downregulating the inflammation-causing pathways in the acute lung injury model [59]. The TNBS-induced ulcerative colitis has also been treated successfully with esculetin revealing the attenuation of COX2 in the inflamed colon [60]. Esculetin reduces the release of soluble intracellular adhesion molecule-1 inhibiting leukocyte and endothelial cell adhesion events therefore inflammation [61].…”

Section: Esculetin In Inflammationmentioning

confidence: 99%

Mechanistic insights into the biochemical and pharmacological profile of esculetin

Garg¹,

Gupta²,

Sahu³

et al. 2022

Preprint

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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, and many others. Glycosides and caffeic acid conjugates are the common forms of esculetin present in medicinal plants. Esculetin acts as an antioxidant, anti-inflammatory, anti-diabetic, anti-hepatic, and anti-cancer agent by inhibiting the production of free radicals, inflammatory mediators, and genes that cause liver diseases and cancer. It also aids in the regulation of blood sugar. Scientists developing pharmaceutical formulations require some rationale and preliminary studies for drug design, but a small number of clinical studies on humans containing esculetin limit its potential for use as a safe alternative drug. Therefore, in this review article, the published studies have been reviewed to identify the pathogenesis of cancer, oxidative stress, inflammation, arthritis, diabetes and fatty liver along with the discussion on potential therapeutic strategies of esculetin. Advancements in our understanding of these diseases will aid in the development of new and innovative medications for treating many ailments. In conclusion, esculetin has immense potential to be used as a safe drug against many diseases but requires further testing and confirmation through clinical trials.

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“…Hypoxia-inducible factor-1 (HIF-1) is known to be the main regulator of hypoxia cell adaptation and vascular endothelial growth factor (VEGF), an effective regulator of barrier protection and the healing of ulcer that is conducive to the therapeutic activity of HIF-1. The downregulation of the HIF-prolyl hydroxylase (HPH) expression by esculetin (200 μM), leading to the activation of the HIF-1-VEGF pathway that triggers beneficial effects to colitis was suggested by Yum et al (2015). In rats with colitis, it was suggested by Witaicenis et al that esculetin with a dosage of 5 mg/kg not only increases the defense against ROS but also inhibits the secretion of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-lβ, IL-2, and interferon (IFN)-γ, leading to the lower activation and less migration of inflammatory cells (Witaicenis et al, 2013).…”

Section: Antiinflammatory Activitymentioning

confidence: 99%

Esculetin: A review of its pharmacology and pharmacokinetics

Zhang

Xie

2021

Phytotherapy Research

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Esculetin is a natural dihydroxy coumarin; it is mainly extracted from twig skin and the trunk bark of the Chinese herbal medicine Fraxinus rhynchophylla Hance. Emerging evidence suggests that esculetin has a wide range of pharmacological activities.Based on its fundamental properties, including antioxidant, antiinflammatory, antiapoptotic, anticancer, antidiabetic, neuroprotective, and cardiovascular protective activities, as well as antibacterial activity, among others, esculetin is expected to be a therapeutic drug for specific disease indications, such as cancer, diabetes, atherosclerosis, Alzheimer's disease (AD), Parkinson's disease (PD), nonalcoholic fatty liver disease (NAFLD), and other diseases. The oral bioavailability of esculetin was shown by studies to be low. The extensive glucuronidation was described to be the main metabolic pathway of esculetin and C-7 phenolic hydroxyl to be its major metabolic site.With the development of scientific research technology, the pharmacological effects of esculetin are identified and its potential for the treatment of diseases is demonstrated. The underlining mechanisms of action and biological activities as well as the pharmacokinetic data of the analyzed compound reported so far are highlighted in this review with the aim of becoming a proven, and applicable insight and reference for further studies on the utilization of esculetin.

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HIF-prolyl hydroxylase is a potential molecular target for esculetin-mediated anti-colitic effects

Cited by 18 publications

References 26 publications

Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation

Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation

Mechanistic insights into the biochemical and pharmacological profile of esculetin

Esculetin: A review of its pharmacology and pharmacokinetics

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