Meng Junjun, Wen Chengquan, Lu Yang, Fan Xiaofan, Dang Ruili, Chu Jianfeng, Jiang Pei, Han Wenxiu, Feng Lei
Translational Pharmaceutical Laboratory, Jining NO.1 People's Hospital, Shandong First Medical University, Jiankang Road, Jining 272000, China.
Shandong Provincial Key Medical and Health Laboratory of Neuroinjury and Repair, Jining NO.1 People's Hospital, Jining, 272000, China.
Food Funct. 2025 Jul 1;16(13):5278-5300. doi: 10.1039/d5fo00425j.
Alliin, a precursor active compound of sulfur-containing organic compounds such as allicin in garlic, is recognized as an important bioactive substance in garlic. Allicin has been shown to have significant neuroprotective effects and promote functional recovery in intracerebral hemorrhage (ICH). As a precursor of many active compounds, alliin may have broader therapeutic effects. Therefore, the aim of this study was to investigate the molecular mechanisms underlying the neuroprotective effects of alliin. In this study, we found that alliin inhibits ferroptosis, thereby exerting neuroprotective effects in ICH. However, the neuroprotective effects of alliin and its pharmacological mechanisms in ferroptosis have not been fully explored. The results showed that alliin significantly inhibited erastin-induced ferroptosis in HT22 cells and suppressed ferroptosis in the brain tissue of collagenase-induced ICH mice, alleviating neurological dysfunction and pathological damage. Mechanistically, alliin downregulated the expression of 15-lipoxygenase (ALOX15), which inhibits phospholipid peroxidation and ferroptosis. Moreover, gene knockout of ALOX15 produced effects similar to those of alliin, and comparable results were obtained using the ferroptosis inhibitor ferrostatin-1. This study is the first to demonstrate that alliin regulates ferroptosis both and . In conclusion, our study highlights ALOX15 as a critical factor in ferroptosis associated with ICH, and shows that alliin exerts neuroprotective effects by inhibiting ALOX15-dependent ferroptosis.
蒜氨酸是大蒜中含硫有机化合物如大蒜素的前体活性化合物，被认为是大蒜中的一种重要生物活性物质。大蒜素已被证明具有显著的神经保护作用，并能促进脑出血（ICH）后的功能恢复。作为许多活性化合物的前体，蒜氨酸可能具有更广泛的治疗作用。因此，本研究的目的是探讨蒜氨酸神经保护作用的分子机制。在本研究中，我们发现蒜氨酸抑制铁死亡，从而在脑出血中发挥神经保护作用。然而，蒜氨酸在铁死亡中的神经保护作用及其药理机制尚未得到充分探索。结果表明，蒜氨酸显著抑制erastin诱导的HT22细胞铁死亡，并抑制胶原酶诱导的脑出血小鼠脑组织中的铁死亡，减轻神经功能障碍和病理损伤。机制上，蒜氨酸下调15-脂氧合酶（ALOX15）的表达，从而抑制磷脂过氧化和铁死亡。此外，ALOX15基因敲除产生了与蒜氨酸相似的效果，使用铁死亡抑制剂ferrostatin-1也得到了类似的结果。本研究首次证明蒜氨酸在体内和体外均能调节铁死亡。总之，我们的研究强调ALOX15是与脑出血相关的铁死亡中的关键因素，并表明蒜氨酸通过抑制ALOX15依赖性铁死亡发挥神经保护作用。
