Esculetin Prevents the Induction of Matrix Metalloproteinase-1 by Hydrogen Peroxide in Skin Keratinocytes

Zhen, Ao Xuan; Piao, Mei Jing; Kang, Kyoung Ah; Fernando, Pincha Devage Sameera Madushan; Kang, Hee Kyoung; Koh, Young Sang; Hyun, Jin Won

doi:10.15430/jcp.2019.24.2.123

Cited by 10 publications

(8 citation statements)

References 32 publications

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“…JNK phosphorylation induces the activation of downstream transcription factor proteins, including AP-1 protein [ 45 ]. AP-1 activation is critical for MMP synthesis [ 47 ]. In our study, we investigated AP-1 activation by evaluating the activation of c-Jun and c-Fos proteins, which are two main components of the AP-1 complex.…”

Section: Discussionmentioning

confidence: 99%

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

et al. 2022

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Particulate matter 2.5 (PM2.5) exposure can trigger adverse health outcomes in the human skin, such as skin aging, wrinkles, pigment spots, and atopic dermatitis. PM2.5 is associated with mitochondrial damage and the generation of reactive oxygen species (ROS). Hesperidin is a bioflavonoid that exhibits antioxidant and anti-inflammatory properties. This study aimed to determine the mechanism underlying the protective effect of hesperidin on human HaCaT keratinocytes against PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence. Human HaCaT keratinocytes were pre-treated with hesperidin and then treated with PM2.5. Hesperidin attenuated PM2.5-induced mitochondrial and DNA damage, G0/G1 cell cycle arrest, and SA-βGal activity, the protein levels of cell cycle regulators, and matrix metalloproteinases (MMPs). Moreover, treatment with a specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, along with hesperidin markedly restored PM2.5-induced cell cycle arrest and cellular senescence. In addition, hesperidin significantly reduced the activation of MMPs, including MMP-1, MMP-2, and MMP-9, by inhibiting the activation of activator protein 1. In conclusion, hesperidin ameliorates PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence in human HaCaT keratinocytes via the ROS/JNK pathway.

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Section: Discussionmentioning

confidence: 99%

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

et al. 2022

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“…In recent years, it has been reported that Esc can improve oxidative stress and apoptosis in H9c2 cells by reducing the phosphorylation level of JNK in order to attenuate myocardial ischemia/reperfusion (I/R) injury [28]. In addition, Esc can protect oxidative stress-induced aging in human HaCaT keratinocytes by decreasing the phosphorylation level of c-Jun and c-Fos and inhibiting the JNK signaling pathway [29]. Thus, we hypothesized that the protective effect of Esc in H 2 O 2 -induced HepG2 cells might be closely associated with the JNK signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells

Luo,

Chang,

Huang

et al. 2024

Molecules

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Oxidative stress plays a crucial role in the pathogenesis of many diseases. Esculetin is a natural coumarin compound with good antioxidant and anti-inflammatory properties. However, whether esculetin can protect HepG2 cells through inhibiting H2O2-induced apoptosis and pyroptosis is still ambiguous. Therefore, this study aimed to investigate the protective effects and mechanisms of esculetin against oxidative stress-induced cell damage in HepG2 cells. The results of this study demonstrate that pretreatment with esculetin could significantly improve the decrease in cell viability induced by H2O2 and reduce intracellular ROS levels. Esculetin not only apparently reduced the apoptotic rates and prevented MMP loss, but also markedly decreased cleaved-Caspase-3, cleaved-PARP, pro-apoptotic protein (Bax), and MMP-related protein (Cyt-c) expression, and increased anti-apoptotic protein (Bcl-2) expression in H2O2-induced HepG2 cells. Meanwhile, esculetin also remarkably reduced the level of LDH and decreased the expression of the pyroptosis-related proteins NLRP3, cleaved-Caspase-1, Il-1β, and GSDMD-N. Furthermore, esculetin pretreatment evidently downregulated the protein expression of p-JNK, p-c-Fos, and p-c-Jun. Additionally, anisomycin, a specific activator of JNK, blocked the protection of esculetin against H2O2-induced HepG2 cells apoptosis and pyroptosis. In conclusion, esculetin can protect HepG2 cells against H2O2-induced oxidative stress, apoptosis, and pyroptosis via inhibiting the JNK signaling pathway. These findings indicate that esculetin has the potential to be used as an antioxidant that improves oxidative stress-related diseases.

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“…It has been found that H 2 O 2 upregulates the expression of MMP-1, thus promoting skin aging and oxidative stress by activating the MAPK and AP1 signaling pathways. The treatment of 5 µg/mL esculetin to H 2 O 2 -induced oxidative stress in HaCaT cells results in the inhibition of MMP-1, phospho-MEK1, phospho-ERK1/2, phospho-SEK1, and phospho-JNK1/2 along with the intracellular Ca 2+ levels [ 62 ]. In addition, esculetin at 50 µL was reported to protect human fibroblast from oxidative stress-induced DNA damage induced by linoleic acid hydroxide and iron (III) ion [ 63 ] ( Table 2 , Figure 3 ).…”

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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Esculetin Prevents the Induction of Matrix Metalloproteinase-1 by Hydrogen Peroxide in Skin Keratinocytes

Cited by 10 publications

References 32 publications

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells

Pharmacological and Therapeutic Applications of Esculetin

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