基于活性成分的多靶点修复：六种天然油脂与大豆异黄酮改善更年期皮肤屏障功能的机制研究进展

Active-Component-Based Multi-Target Repair: Advances in the Mechanisms by Which Six Natural Oils and Soy Isoflavones Improve Skin Barrier Function during Menopause

摘要: 更年期女性因卵巢功能衰退、雌激素与孕激素水平改变，可出现角质层含水量下降、经皮水分丢失(transepidermal water loss, TEWL)升高、脂质屏障重建减慢、炎症阈值降低和胶原基质降解增强等皮肤改变。天然油脂和大豆异黄酮的屏障保护潜力主要来源于其活性成分与更年期皮肤病理环节之间的对应关系。亚油酸(LA)可参与ω-羟基神经酰胺和角质层脂质结构形成，是屏障脂质重建的核心脂肪酸；γ-亚麻酸(GLA)及其代谢物二高-γ-亚麻酸(DGLA)有利于形成偏抗炎的二十碳烷酸谱；α-亚麻酸(ALA)和其他多不饱和脂肪酸可通过PPAR、MAPK/NF-κB和氧化应激相关通路参与炎症控制；磷脂、卵磷脂和胆固醇可支持脂质双层、层状液晶结构和活性物递送；植物甾醇、类胡萝卜素、维生素E、角鲨烯及棕榈油酸等成分则分别对应抗炎、抗氧化、膜脂保护、皮脂膜模拟和黏膜/皮肤干燥改善。基于上述成分基础，富含LA和GLA的月见草油、琉璃苣籽油，富含ALA和LA的印加果籽油，富含棕榈油酸、类胡萝卜素和植物甾醇的沙棘果油，富含磷脂、胆固醇、类胡萝卜素及微量甾体成分的蛋黄油，以及具有长链脂肪酸稳定油膜优势的白池花籽油，均具备改善更年期皮肤屏障功能的明确机制基础和潜在应用优势。大豆异黄酮则可通过ERβ相关调控、NF-κB抑制、Nrf2/ARE抗氧化防御及胶原/弹性纤维代谢调节，与天然油脂形成“外源性脂质补充–内源性信号调控”的互补策略。本文系统综述天然油脂与大豆异黄酮在更年期皮肤屏障护理中的作用机制，为复合制剂开发、功效成分筛选和后续临床终点设计提供依据。

Abstract: Women undergoing menopause may experience a range of skin changes due to declining ovarian function and alterations in estrogen and progesterone levels, including reduced stratum corneum hydration, increased transepidermal water loss (TEWL), delayed lipid barrier restoration, a lowered inflammatory threshold, and accelerated degradation of the collagen matrix. The barrier-protective potential of natural oils and soy isoflavones is primarily attributable to the correspondence between their bioactive components and the pathological processes affecting menopausal skin. Linoleic acid (LA) contributes to the formation of ω-hydroxyceramides and the lipid architecture of the stratum corneum, making it a key fatty acid for epidermal barrier lipid reconstruction. γ-Linolenic acid (GLA) and its metabolite dihomo-γ-linolenic acid (DGLA) facilitate the generation of a more anti-inflammatory eicosanoid profile. α-Linolenic acid (ALA) and other polyunsaturated fatty acids contribute to inflammation control through pathways associated with peroxisome proliferator-activated receptors (PPARs), MAPK/NF-κB signaling, and oxidative stress. Phospholipids, lecithin, and cholesterol support the formation of lipid bilayers and lamellar liquid-crystalline structures while facilitating the delivery of bioactive compounds. Phytosterols, carotenoids, vitamin E, squalene, and palmitoleic acid exert anti-inflammatory and antioxidant effects, protect membrane lipids, mimic the natural sebum film, and alleviate mucosal and cutaneous dryness. On the basis of these compositional characteristics, evening primrose oil and borage seed oil, which are rich in LA and GLA; sacha inchi seed oil, which is rich in ALA and LA; sea buckthorn fruit oil, which contains abundant palmitoleic acid, carotenoids, and phytosterols; egg yolk oil, which is rich in phospholipids, cholesterol, carotenoids, and trace steroidal components; and meadowfoam seed oil, which forms a stable lipid film because of its high content of long-chain fatty acids, all possess a well-defined mechanistic basis and potential advantages for improving menopausal skin barrier function. Soy isoflavones may regulate estrogen receptor beta (ERβ)-related signaling, inhibit NF-κB activation, enhance Nrf2/antioxidant response element (ARE)-mediated antioxidant defense, and modulate collagen and elastic-fiber metabolism. They may therefore complement natural oils through an integrated strategy combining exogenous lipid supplementation with endogenous signaling regulation. This review systematically summarizes the mechanisms by which natural oils and soy isoflavones support skin barrier care during menopause and provides a theoretical basis for the development of combination formulations, the selection of functional ingredients, and the design of clinical endpoints in future studies.