Diosmetin, a novel transient receptor potential vanilloid 1 antagonist, alleviates the UVB radiation-induced skin inflammation in mice

Camponogara, Camila; Pegoraro, Natháli Schopf; Brusco, Indiara; Brucker, Natália; Oliveira, Sara Marchesan

doi:10.1007/s10787-021-00802-1

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…UVB radiation exposure triggers skin inflammation that involves processes such as vasodilation, which leads to edema development, erythema, inflammatory cell infiltration, inflammatory cytokines/chemokines release, epidermal hyperplasia, and oxidative stress, besides skin photoaging and photocarcinogenesis [ 15 , 21 , 22 , 30 , 66 , 67 ]. So, restricting acute skin inflammation is extremely important to avoid it from becoming chronic.…”

Section: Discussionmentioning

confidence: 99%

“…Besides the results mentioned above, other alternative biologically active compounds, such as coenzyme Q10 and vitamin E acetate [ 21 ], plant derivatives [ 22 , 23 ], and emergent immunotherapies [ 24 , 25 ], effectively reduce skin inflammatory processes. We also previously showed the efficacy of oleic acid (OA), a natural compound present in several vegetable oils [ 26 , 27 , 28 , 29 ], in inhibiting skin inflammatory processes induced by UVB radiation and by irritant agent croton oil in mice [ 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

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The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice

Pegoraro,

Gehrcke,

Camponogara

et al. 2024

Pharmaceutics

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Dexamethasone has a high anti-inflammatory efficacy in treating skin inflammation. However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 ± 3.77% and 85.11 ± 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 ± 4.29% and 27.60 ± 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice

Pegoraro,

Gehrcke,

Camponogara

et al. 2024

Pharmaceutics

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“…Besides the TRPV3 channel, other TRP channels, such as TRPV4, TRPA1, TRPV1, TRPM8, and TRPC7, have also been reported for their involvement in UV-induced melanin formation and deposition, photoaging, and sunburn pain. 14,30,[44][45][46][47][48] As a warmth-sensitive channel, TRPV3 appears to play a critical role in UVBinduced skin inflammation in comparison to other calcium permeable channels. Although other TRP channels are expressed, their expression levels are relatively low in comparison with TRPV3 that is robustly expressed in the keratinocytes that absorb the majority of ultraviolet radiation.…”

Section: Discussionmentioning

confidence: 99%

“…The polymodal TRP ion channels are expressed in many cell types including keratinocytes, melanocytes, sensory neurons, and immune cells in the skin where they function as cellular sensors in response to chemical and environmental stimuli. Besides the TRPV3 channel, other TRP channels, such as TRPV4, TRPA1, TRPV1, TRPM8, and TRPC7, have also been reported for their involvement in UV‐induced melanin formation and deposition, photoaging, and sunburn pain 14,30,44–48 . As a warmth‐sensitive channel, TRPV3 appears to play a critical role in UVB‐induced skin inflammation in comparison to other calcium permeable channels.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of cutaneous heat‐sensitive Ca²⁺‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

Qu,

Sun,

Wei

et al. 2023

The FASEB Journal

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Ultraviolet B (UVB) radiation causes skin injury by trigging excessive calcium influx and signaling cascades in the skin keratinocytes. The heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 (TRPV3) channels robustly expressed in the keratinocytes play an important role in skin barrier formation and wound healing. Here, we report that inhibition of cutaneous TRPV3 alleviates UVB radiation‐induced skin lesions. In mouse models of ear swelling and dorsal skin injury induced by a single exposure of weak UVB radiation, TRPV3 genes and proteins were upregulated in quantitative real‐time PCR and Western blot assays. In accompany with TRPV3 upregulations, the expressions of proinflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) were also increased. Knockout of the TRPV3 gene alleviates UVB‐induced ear swelling and dorsal skin inflammation. Furthermore, topical applications of two selective TRPV3 inhibitors, osthole and verbascoside, resulted in a dose‐dependent attenuation of skin inflammation and lesions. Taken together, our findings demonstrate the causative role of overactive TRPV3 channel function in the development of UVB‐induced skin injury. Therefore, topical inhibition of TRPV3 may hold potential therapy or prevention of UVB radiation‐induced skin injury.

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“…TRP channels, such as TRPV1, are activated by ROS induced by blue light [ 107 ] and can be blocked by its antagonist after UV exposure [ 108 ]. They also have been associated with growth stimuli.…”

Section: Cells and Their Trp Expression In The Trachea And Bronchimentioning

confidence: 99%

Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

Müller¹,

Alt²,

Rajan³

et al. 2022

Cells

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Our respiratory system is exposed to toxicants and pathogens from both sides: the airways and the vasculature. While tracheal, bronchial and alveolar epithelial cells form a natural barrier in the airways, endothelial cells protect the lung from perfused toxic compounds, particulate matter and invading microorganism in the vascular system. Damages induce inflammation by our immune response and wound healing by (myo)fibroblast proliferation. Members of the transient receptor potential (TRP) superfamily of ion channel are expressed in many cells of the respiratory tract and serve multiple functions in physiology and pathophysiology. TRP expression patterns in non-neuronal cells with a focus on TRPA1, TRPC6, TRPM2, TRPM5, TRPM7, TRPV2, TRPV4 and TRPV6 channels are presented, and their roles in barrier function, immune regulation and phagocytosis are summarized. Moreover, TRP channels as future pharmacological targets in chronic obstructive pulmonary disease (COPD), asthma, cystic and pulmonary fibrosis as well as lung edema are discussed.

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Diosmetin, a novel transient receptor potential vanilloid 1 antagonist, alleviates the UVB radiation-induced skin inflammation in mice

Cited by 12 publications

References 38 publications

The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice

The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice

Inhibition of cutaneous heat‐sensitive Ca²⁺‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

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Diosmetin, a novel transient receptor potential vanilloid 1 antagonist, alleviates the UVB radiation-induced skin inflammation in mice

Cited by 12 publications

References 38 publications

The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice

The Association of Oleic Acid and Dexamethasone Acetate into Nanocapsules Enables a Reduction in the Effective Corticosteroid Dose in a UVB Radiation-Induced Sunburn Model in Mice

Inhibition of cutaneous heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

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Inhibition of cutaneous heat‐sensitive Ca²⁺‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice