Regulatory Role of Nrf2 Signaling Pathway in Wound Healing Process

Süntar, İpek; Çetinkaya, Sümeyra; Panieri, Emiliano; Saha, Sarmistha; Buttari, Brigitta; Saso, Luciano

doi:10.3390/molecules26092424

Cited by 41 publications

(23 citation statements)

References 122 publications

(116 reference statements)

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“…Nrf2 negatively regulated the NF-κB signaling pathway and proinflammatory cytokine production by inhibiting oxidative stress-induced NF-κB and preventing the IκB-α (NF-κB inhibitor) proteasomal degradation ( Ma, 2013 ; Saha et al, 2020 ). In addition, several proinflammatory cytokines (e.g., IL-6, TNF-α and IL-1β), growth factors (e.g., epidermal growth factor (EGF), fibroblast growth factor, keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF) and MMPs (e.g., MMP-2 and MMP-9) play a role in wound repair consisting of a series of multiple stages including inflammation, proliferation and remodeling ( Shao et al, 2019 ; Suntar et al, 2021 ). Activation of Nrf2 in response to ROS production in inflamed tissues is thus suggested to play a role in promoting wound healing and regulating repair-related inflammation.…”

Section: Introductionmentioning

confidence: 99%

Role of Phytochemicals in Skin Photoprotection via Regulation of Nrf2

Chaiprasongsuk

Panich

2022

Front. Pharmacol.

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Ethnopharmacological studies have become increasingly valuable in the development of botanical products and their bioactive phytochemicals as novel and effective preventive and therapeutic strategies for various diseases including skin photoaging and photodamage-related skin problems including abnormal pigmentation and inflammation. Exploring the roles of phytochemicals in mitigating ultraviolet radiation (UVR)-induced skin damage is thus of importance to offer insights into medicinal and ethnopharmacological potential for development of novel and effective photoprotective agents. UVR plays a role in the skin premature aging (or photoaging) or impaired skin integrity and function through triggering various biological responses of skin cells including apoptosis, oxidative stress, DNA damage and inflammation. In addition, melanin produced by epidermal melanocytes play a protective role against UVR-induced skin damage and therefore hyperpigmentation mediated by UV irradiation could reflect a sign of defensive response of the skin to stress. However, alteration in melanin synthesis may be implicated in skin damage, particularly in individuals with fair skin. Oxidative stress induced by UVR contributes to the process of skin aging and inflammation through the activation of related signaling pathways such as the mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1), the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), the nuclear factor kappa B (NF-κB) and the signal transducer and activator of transcription (STAT) in epidermal keratinocytes and dermal fibroblasts. ROS formation induced by UVR also plays a role in regulation of melanogenesis in melanocytes via modulating MAPK, PI3K/Akt and the melanocortin 1 receptor (MC1R)-microphthalmia-associated transcription factor (MITF) signaling cascades. Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated antioxidant defenses can affect the major signaling pathways involved in regulation of photoaging, inflammation associated with skin barrier dysfunction and melanogenesis. This review thus highlights the roles of phytochemicals potentially acting as Nrf2 inducers in improving photoaging, inflammation and hyperpigmentation via regulation of cellular homeostasis involved in skin integrity and function. Taken together, understanding the role of phytochemicals targeting Nrf2 in photoprotection could provide an insight into potential development of natural products as a promising strategy to delay skin photoaging and improve skin conditions.

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Section: Introductionmentioning

confidence: 99%

Role of Phytochemicals in Skin Photoprotection via Regulation of Nrf2

Chaiprasongsuk

Panich

2022

Front. Pharmacol.

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“…Therefore, proper regulation of oxidative stress in wound microenvironment may play a positive role in promoting wound healing. Recent researches reported that Nrf-2 plays a vital role in alleviating oxidative stress and promoting wound healing [ 11 , 12 ]. The Nrf-2 signal pathway participates in the regulation of antioxidative gene expression and thus improves the cell protection [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway

Shen

Zhou

et al. 2022

Oxidative Medicine and Cellular Longevity

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Wound healing is a complex dynamic process involving a large number of biological events. Excessive oxidative stress is a key factor delaying wound healing. Hydrogen is an antioxidant, anti-inflammatory, and antiapoptotic medical gas with safety, effectiveness, and penetrability. However, the effects of local treatment of hydrogen on wound healing and its potential mechanisms remain unclear. In this study, Kunming (KM) mice were used to set up a wound model. All the mice were randomly divided into the control, the local treatment with saline group, the local treatment with the hydrogen-rich saline group, and the intraperitoneal injection of the hydrogen-rich saline group. To evaluate the impact of hydrogen-rich saline on wound healing, we assessed the wound healing rate, wound closure time, histomorphology, oxidative stress indicators, inflammatory cytokines, the apoptosis index, and the expression of the nuclear factor-erythroid-related factor 2(Nrf-2). Furthermore, the immortalized nontumorigenic human epidermal (HaCaT) cells were chosen to investigate the therapeutic effects of hydrogen-rich medium on oxidative stress and its underlying mechanisms. The results showed that local treatment of hydrogen-rich saline shortened wound closure time and reduced the level of proinflammatory cytokines and lipid peroxidation. Meanwhile, it decreased the cell apoptosis index and increased the Nrf-2 expression. Besides, hydrogen-rich medium relieved the oxidative stress via the activation of the Nrf-2/heme oxygenase-1 (HO-1) pathway. In conclusion, local treatment of hydrogen-rich saline exhibits the healing-promoting function through antioxidant, anti-inflammatory, and antiapoptotic effects. Hydrogen relieves the oxidative stress in the wound microenvironment via Nrf-2/HO-1 signaling pathway. This study may offer a new strategy to promote wound healing and a new perspective to illustrate the mechanism of wound healing.

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“…Increasing the GSH/GSSG ratio can attenuate the oxidative damage of ROS on osteoblasts via the PI3K/Akt-Nrf2 signaling pathways ( Casati et al, 2020 ). Nrf2 is a nuclear factor that regulates gene encoding proteins involved in the response to injury and inflammation, including the production of free radicals ( Süntar et al, 2021 ). When the PI3K/AKT pathway located on the cell membrane is activated, the signal is transmitted to the cytoplasm to release Nrf2 anchored by Kelch-like ECH-associated protein 1 (Keap1) ( Chen et al, 2021a ).…”

Section: Antioxidant Substancesmentioning

confidence: 99%

Three Classes of Antioxidant Defense Systems and the Development of Postmenopausal Osteoporosis

et al. 2022

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Osteoporosis is a common bone imbalance disease that threatens the health of postmenopausal women. Estrogen deficiency accelerates the aging of women. Oxidative stress damage is regarded as the main pathogenesis of postmenopausal osteoporosis. The accumulation of reactive oxygen species in the bone microenvironment plays a role in osteoblast and osteoclast apoptosis. Improving the oxidative state is essential for the prevention and treatment of postmenopausal osteoporosis. There are three classes of antioxidant defense systems in the body to eliminate free radicals and peroxides including antioxidant substances, antioxidant enzymes, and repair enzymes. In our review, we demonstrated the mechanism of antioxidants and their effect on bone metabolism in detail. We concluded that glutathione/oxidized glutathione (GSH/GSSG) conversion involved the PI3K/Akt-Nrf2/HO-1 signaling pathway and that the antioxidant enzyme-mediated mitochondrial apoptosis pathway of osteoblasts was necessary for the development of postmenopausal osteoporosis. Since the current therapeutic effects of targeting bone cells are not significant, improving the systemic peroxidation state and then regulating bone homeostasis will be a new method for the treatment of postmenopausal osteoporosis.

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Regulatory Role of Nrf2 Signaling Pathway in Wound Healing Process

Cited by 41 publications

References 122 publications

Role of Phytochemicals in Skin Photoprotection via Regulation of Nrf2

Role of Phytochemicals in Skin Photoprotection via Regulation of Nrf2

Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway

Three Classes of Antioxidant Defense Systems and the Development of Postmenopausal Osteoporosis

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