青皮提取物缓解皮肤敏感的作用机制研究

doi:10.3969/j.issn.1001-1803.2022.04.011

摘要/Abstract

摘要：

青皮提取物（CR）是将未成熟的柑橘幼果经过特定工艺制备而成,富含黄酮和生物碱。本项目通过瞬时电位受体香草酸亚型1（TRPV1）高表达细胞、前列腺素受体1（EP1）高表达细胞、神经母细胞,研究CR通过TRPV1缓解皮肤敏感的作用机制。于TRPV1高表达细胞和正常细胞上对比研究发现,辣椒素（CAP）、苯氧乙醇可通过激活TRPV1引起伤害性细胞因子白介素8、趋化因子MCP-1、前列腺素E2（PGE-2）的表达量增加,细胞划痕损伤后的迁移速度下降。而CR能显著降低细胞因子的过表达,特别是针对PGE-2,也可加速划痕损伤后的细胞迁移。再对PGE-2-EP1信号通路进行研究发现,0.5%体积分数的CR也可显著抑制PGE-2通过其受体EP1引发的荧光素酶激活。最后于神经母细胞上进行验证,发现0.06%~0.25%体积分数的CR也能抑制CAP、苯氧乙醇通过激活TRPV1导致的细胞外Ca²⁺内流,进而抑制皮肤敏感或受刺激后的信号传导,最终缓解皮肤热、痒、痛等症状。因此,CR可通过调控TRPV1激活,进而抑制伤害性细胞因子分泌及下游信号传导,促进皮肤屏障修复,缓解皮肤因受到外界刺激过度反应后,导致的敏感和刺激。

关键词: 青皮提取物, 皮肤敏感, 屏障修复

Abstract:

Citrus reticulata （Tangerine） extract （CR） was prepared according to a proprietary process from immature citrus fruit and it was rich in flavonoids and alkaloids. To investigate the mechanism of CR in relieving skin sensitivity through transient receptor potential vanilloid 1 （TRPV1）, TRPV1 over-expression cells, prostaglandin receptor 1（EP1） over-expression cells and neuroblast cells were prepared. A comparison between normal cells and TRPV1 over-expression cells showed that, capsaicin （CAP） and phenoxyethanol could increase the expression of interleukin 8, chemokine MCP-1 and prostaglandin E2 （PGE-2） by activating TRPV1 and decrease the migration rate of wound healing. However, the results showed that CR could significantly inhibit the overexpression of cytokines, especially for PGE-2, and could also promote the migration rate of wound healing. Furthermore, the PGE-2-EP1 signaling pathway was studied, and it was found that 0.5% volume fraction of CR could significantly inhibit the activation of luciferase induced by PGE-2 through its receptor EP1. Finally, it was verified on neuroblast cells, and it was found that 0.06%-0.25% volume fraction of CR could inhibit the extracellular Ca²⁺ influx induced by the activation of TRPV1 caused by CAP and phenoxyethanol, and then inhibit the signal transduction in skin sensitivity or skin irritation, and finally alleviate clinical symptoms such as heat, itching and pain. Therefore, through the control of the activation of TRPV1, CR can inhibit the secretion of nociceptive cytokines and the downstream signal transduction, promote skin barrier repair, and alleviate skin irritation and sensitivity caused by the external stimuli.

Key words: Citrus reticulata extract, sensitive skin, skin barrier repair

中图分类号:

TQ658

周利丹,卢伊娜,刘青. 青皮提取物缓解皮肤敏感的作用机制研究[J]. 日用化学工业, 2022, 52(4): 418-424.

Zhou Lidan,Lu Yina,Liu Qing. Mechanism of Citrus reticulata extract in relieving skin sensitivity[J]. China Surfactant Detergent & Cosmetics, 2022, 52(4): 418-424.

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表达量/ （pg/mL）	HaCaT细胞			HaCaT-TRPV1-OE细胞
表达量/ （pg/mL）	Control	20 μmol/L CAP	20 μmol/L CAP+0.125% CR	Control	20 μmol/L CAP	20 μmol/L CAP+0.125% CR	抑制率/%
IL-8	154.49	173.64	202.16	179.55	543.61	231.89^***	57.34
MCP-1	2 814.48	4 013.40	2 469.47^***	2 962.27	5 167.17	2 045.93^***	60.41
PGE-2	210.70	215.45	190.71	1 053.86	1 704.14	875.48^***	48.63

表达量/ （pg/mL）	HaCaT细胞			HaCaT-TRPV1-OE细胞
表达量/ （pg/mL）	Control	苯氧乙醇	苯氧乙醇+0.125% CR	Control	苯氧乙醇	苯氧乙醇+0.125% CR	抑制率/%
IL-8	160.81	124.41	142.61	192.22	322.99	237.40^**	26.50
MCP-1	3 025.53	3 158.08	1 887.68^***	3 301.88	4 359.68	2 451.50^***	43.77
PGE-2	75.81	140.47	112.73^*	797.95	927.08	599.52^***	35.33