Mese-Tayfur Seher, Demirel-Yalcıner Tugce, Migni Anna, Bartolini Desirée, Galli Francesco, Ozer Nesrin Kartal, Sozen Erdi
Department of Biochemistry, Faculty of Medicine, Marmara University, Istanbul, Turkey.
Institute of Health Sciences, Marmara University, Istanbul, Turkey.
Free Radic Res. 2025 Jan;59(1):86-101. doi: 10.1080/10715762.2024.2449457. Epub 2025 Jan 8.
Naturally occurring vitamin E is a lipophilic plant-derived molecule corresponding to the 2 R forms of alpha-tocopherol. A series of natural analogs or tocochromanols are present in nature, including β-, γ- and δ-tocopherol (βT, γT, δT), the corresponding tocotrienols (αTE, βTE, γTE, δTE) and tocomonoenols. Differences between these analogs as lipophilic antioxidants and modulators of molecular processes suggest specific therapeutic properties against various disorders associated with acute and chronic inflammation. However, hepatic metabolism of these compounds cytochrome P450-initiated side chain ω-oxidation involves the production of long-chain metabolites (LCMs) followed by intermediate (ICMs) and short-chain metabolites (SCMs), respectively. Despite the initial studies indicating these metabolites as catabolic-end products, recent findings identify their importance in providing biological functions. In this scope, LCMs, especially 13'-carboxychromanols (13'-COOHs), have been reported to hold stronger anti-inflammatory capacity than their unmetabolized precursors due to their ability to inhibit 5-lipoxygenase and cyclooxygenase-catalyzed eicosanoid formation, as well as their modulation of the pro-inflammatory transcriptional protein nuclear factor κB (NF-κB). Also, these LCMs have been reported to enhance detoxification and lipid metabolism pathways associated with cellular inflammation by modulating the nuclear receptors peroxisome proliferator-activated receptor-γ (PPARγ) and pregnane x receptor (PXR). These properties of LCMs will be described in this narrative review article focusing on recent information regarding their bioavailability, anti-inflammatory effects, and mechanisms of action in acute and chronic inflammatory disorders.
天然存在的维生素E是一种亲脂性的植物衍生分子，对应于α-生育酚的2R形式。自然界中存在一系列天然类似物或生育三烯酚，包括β-、γ-和δ-生育酚（βT、γT、δT）、相应的生育三烯酚（αTE、βTE、γTE、δTE）和生育单烯酚。这些类似物作为亲脂性抗氧化剂和分子过程调节剂的差异表明，它们对与急慢性炎症相关的各种疾病具有特定的治疗特性。然而，这些化合物的肝脏代谢——细胞色素P450启动的侧链ω-氧化分别涉及长链代谢物（LCMs）、中间代谢物（ICMs）和短链代谢物（SCMs）的产生。尽管最初的研究表明这些代谢物是分解代谢终产物，但最近的研究发现它们在提供生物学功能方面具有重要意义。在这方面，据报道，LCMs，尤其是13'-羧基色满醇（13'-COOHs），由于其抑制5-脂氧合酶和环氧化酶催化的类花生酸形成的能力，以及对促炎转录蛋白核因子κB（NF-κB）的调节作用，其抗炎能力比未代谢的前体更强。此外，据报道，这些LCMs通过调节核受体过氧化物酶体增殖物激活受体-γ（PPARγ）和孕烷X受体（PXR），增强了与细胞炎症相关的解毒和脂质代谢途径。本文将在这篇叙述性综述文章中描述LCMs的这些特性，重点关注其生物利用度、抗炎作用以及在急慢性炎症性疾病中的作用机制的最新信息。
