Topical administration of Esculetin as a potential therapy for experimental dry eye syndrome

Jiang, Dongmei; Liu, X; Hu, Jisheng

doi:10.1038/eye.2017.117

Cited by 10 publications

(6 citation statements)

References 41 publications

(39 reference statements)

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“…Therefore, evaluation of inflammatory cytokines in the ocular surface epithelial (epithelium of cornea or conjunctiva) cells, such as IL-1β, IL-8, TNF-α, and matrix metalloproteinases (MMPs), is the most common feature in experimental models [81,84,[138][139][140]. Alongside the underlying stimulating factors of inflammation in the ocular surface, such as MAP kinase pathways (ERK, JNK, and P38) [140,148], NFkB has also been measured by many researchers. Since ocular surface stress and inflammation induce apoptosis, apoptosis-related factors BAX, BCl2, and their ratio were also measured [88].…”

Section: Analysis Of Molecular Changes and Histopathological Changesmentioning

confidence: 99%

“…In DED, goblet cells were also reduced, which is responsible for mucin secretion. Conjunctival impression cytology (CIC) using hematoxylin and periodic acid-Schiff (PAS) reagent [79,148] or counting goblet cells in the conjunctiva using periodic acid-Schiff (PAS) staining [44,84]. Immunohistochemical slides were also stained with MUC5AC in the conjunctiva to count the goblet cells [79,83,138].…”

Section: Analysis Of Molecular Changes and Histopathological Changesmentioning

confidence: 99%

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Experimental Models, Induction Protocols, and Measured Parameters in Dry Eye Disease: Focusing on Practical Implications for Experimental Research

Rahman

Kim

2021

IJMS

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Dry eye disease (DED) is one of the major ophthalmological healthcare challenges worldwide. DED is a multifactorial disease characterized by a loss of homeostasis of the tear film, and its main pathogenesis is chronic ocular surface inflammation related with various cellular and molecular signaling cascades. The animal model is a reliable and effective tool for understanding the various pathological mechanisms and molecular cascades in DED. Considerable experimental research has focused on developing new strategies for the prevention and treatment of DED. Several experimental models of DED have been developed, and different animal species such as rats, mice, rabbits, dogs, and primates have been used for these models. Although the basic mechanisms of DED in animals are nearly identical to those in humans, proper knowledge about the induction of animal models is necessary to obtain better and more reliable results. Various experimental models (in vitro and in vivo DED models) were briefly discussed in this review, along with pathologic features, analytical approaches, and common measurements, which will help investigators to use the appropriate cell lines, animal, methods, and evaluation parameters depending on their study design.

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Section: Analysis Of Molecular Changes and Histopathological Changesmentioning

confidence: 99%

Section: Analysis Of Molecular Changes and Histopathological Changesmentioning

confidence: 99%

Experimental Models, Induction Protocols, and Measured Parameters in Dry Eye Disease: Focusing on Practical Implications for Experimental Research

Rahman

Kim

2021

IJMS

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“…The inhibition of phosphorylation of the p38 downstream substrate MAPKAPK2 reduced inflammation and ocular surface damage in a DED mouse model [160]. In a rabbit DED model, the Chinese plant, Esculetin, reduced inflammation and dry eye symptoms through specific inhibition of the ERK1/2 pathway [161], and recently it has been reported that an oral administration of Dendrobium officinale extract downregulated the phosphorylation of ERK in human corneal keratocytes and upregulated various aquaporins, while its oral administration in rats enhanced tear production and had a protective effect on ocular surface damage [162]. Accordingly, the levels of the three MAPK signaling pathways and inflammation were rapidly increased in a mouse DED model and remain elevated after 5 days [158].…”

Section: Mapk In the Corneamentioning

confidence: 99%

MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges

Moustardas

Aberdam

Lagali

2023

Cells

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Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors.

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“…For example, esculetin (20-60 mg/kg) can inhibit the production of inflammatory factors such as IL-1β, IL-6, TNF-α, C-C motif chemokine ligand 2 and iNOS in Escherichia coli-induced sepsis mice by inhibiting the NF-κB and STAT1/STAT3 signaling pathways (95). In a rabbit model in which the primary lacrimal gland, sclerotial gland, and cornea were removed to induce dry eye, esculetin (0.05% of the diet) was able to inhibit the expression of IL-1α, IL-1β, and TNF-α by inhibiting the ERK1/2 signaling pathway and thereby suppressing IL-1α, IL-1β, and TNF-α (96). Furthermore, esculetin (10-20 mg/kg) inhibits the expression of TNF-α and IL-6 in isoproterenol induced myocardial toxicity in rats by inhibiting the activation of the NF-κB signaling pathway (97).…”

Section: Lung Inflammationmentioning

confidence: 99%

Antioxidant and anti‑inflammatory effects of esculin and esculetin (Review)

Ju,

Tan,

Wang

et al. 2024

Exp Ther Med

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Fraxinus chinensis Roxb is a deciduous tree, which is distributed worldwide and has important medicinal value. In Asia, the bark of Fraxinus chinensis Roxb is a commonly used traditional Chinese medicine called Qinpi. Esculetin is a coumarin compound derived from the bark of Fraxinus chinensis Roxb and its glycoside form is called esculin. The aim of the present study was to systematically review relevant literature on the antioxidant and anti-inflammatory effects of esculetin and esculin. Esculetin and esculin can promote the expression of various endogenous antioxidant proteins, such as superoxide dismutase, glutathione peroxidase and glutathione reductase. This is associated with the activation of the nuclear factor erythroid-derived factor 2-related factor 2 signaling pathway. The anti-inflammatory effects of esculetin and esculin are associated with the inhibition of the nuclear factor κ-B and mitogen-activated protein kinase inflammatory signaling pathways. In various inflammatory models, esculetin and esculin can reduce the expression levels of various proinflammatory factors such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6, thereby inhibiting the development of inflammation. In summary, esculetin and esculin may be promising candidates for the treatment of numerous diseases associated with inflammation and oxidative stress, such as ulcerative colitis, acute lung and kidney injury, lung cancer, acute kidney injury. Contents 1. Introduction 2. Antioxidant activities of esculin and esculetin 3. Anti-inflammatory activities of esculetin and esculin 4. Conclusion and future perspectives

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Topical administration of Esculetin as a potential therapy for experimental dry eye syndrome

Cited by 10 publications

References 41 publications

Experimental Models, Induction Protocols, and Measured Parameters in Dry Eye Disease: Focusing on Practical Implications for Experimental Research

Experimental Models, Induction Protocols, and Measured Parameters in Dry Eye Disease: Focusing on Practical Implications for Experimental Research

MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges

Antioxidant and anti‑inflammatory effects of esculin and esculetin (Review)

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