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香叶木素,一种新型瞬时受体电位香草素 1 拮抗剂,可缓解 UVB 辐射引起的小鼠皮肤炎症。

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

机构信息

Laboratory Neurotoxicity and Psychopharmacology, Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.

Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.

出版信息

Inflammopharmacology. 2021 Jun;29(3):879-895. doi: 10.1007/s10787-021-00802-1. Epub 2021 Mar 22.

DOI:10.1007/s10787-021-00802-1
PMID:33751333
Abstract

UVB radiation-mediated inflammation and the oxidative process involve the transient receptor potential vanilloid 1 (TRPV1) channel activation in neuronal and non-neuronal cells. Once diosmetin has been identified as a novel TRPV1 antagonist, we evaluated the action of diosmetin from the inflammatory [ear oedema, myeloperoxidase (MPO) activity, histological changes, and cytokines levels] and oxidative [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and SOD activities] parameters in mice exposed to UVB radiation (0.5 j/cm). We also verified the action of diosmetin on UVB radiation-induced inflammatory parameters after cutaneous nerve fibers denervation by RTX (50 µg/kg s.c.). The topical treatment with the novel TRPV1 antagonist, diosmetin (1%; 15 mg/ear), reduced ear oedema, MPO activity, and MIP-2 and IL-1β cytokines levels by 82 ± 8%, 59 ± 10%, 40 ± 12%, and 85 ± 9%, respectively. The action of diosmetin on ear oedema and inflammatory cell infiltration was histologically confirmed. Topical diosmetin (1%) also reduced NADPH oxidase activity by 67 ± 10% and reverted SOD activity by 81 ± 13%. After cutaneous nerve fibers denervation using RTX, diosmetin reduced ear oedema, but not the inflammatory cell infiltration in mice exposed to UVB radiation. Diosmetin can be a promising molecule against skin inflammatory disorders as a result of sunburn induced by UVB radiation exposure.

摘要

UVB 辐射介导的炎症和氧化过程涉及神经元和非神经元细胞中瞬时受体电位香草酸 1(TRPV1)通道的激活。一旦鉴定出大豆黄素是一种新型 TRPV1 拮抗剂,我们就评估了大豆黄素对暴露于 UVB 辐射(0.5 j/cm)的小鼠的炎症[耳部水肿、髓过氧化物酶(MPO)活性、组织学变化和细胞因子水平]和氧化[烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶和 SOD 活性]参数的作用。我们还通过 RTX(50 μg/kg sc)验证了大豆黄素对 UVB 辐射诱导的皮肤神经纤维去神经后炎症参数的作用。新型 TRPV1 拮抗剂大豆黄素(1%;15 mg/耳)的局部治疗可使耳部水肿、MPO 活性、MIP-2 和 IL-1β细胞因子水平分别降低 82±8%、59±10%、40±12%和 85±9%。组织学证实了大豆黄素对耳部水肿和炎症细胞浸润的作用。局部大豆黄素(1%)还可使 NADPH 氧化酶活性降低 67±10%,SOD 活性恢复 81±13%。使用 RTX 对皮肤神经纤维进行去神经后,大豆黄素可减轻暴露于 UVB 辐射的小鼠的耳部水肿,但不能减轻炎症细胞浸润。大豆黄素可能是一种有前途的分子,可用于治疗因暴露于 UVB 辐射而引起的晒伤引起的皮肤炎症性疾病。

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