College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, China.
Food Funct. 2023 Jul 17;14(14):6730-6744. doi: 10.1039/d3fo00750b.
Endometriosis is an estrogen-dependent chronic inflammatory gynecological disease defined by the presence of endometrial glands and mesenchyme outside the uterine cavity, named ectopic endometrium. Recent studies showed that endometriosis is associated with hormone imbalance, inflammation and oxidative stress. As the main component of vanilla bean extract, vanillin is widely used as a flavoring agent in the food, pharmaceutical, and cosmetic industries. It is known for its anti-inflammatory, antibacterial, and antitumor properties, but its therapeutic efficacy in endometriosis has not been studied. In this study, we evaluated the roles of vanillin in this disease using an induced endometriotic mouse model. The results showed that vanillin significantly inhibited the growth of endometrial lesions. Compared with the control group, the weight and volume of lesions were reduced considerably in the vanillin-treated group, showing its fantastic ability to inhibit cell proliferation and promote apoptosis. In addition, in the treatment group, mRNA expression of the pro-inflammatory cytokines , , , and was reduced, the number of macrophages and neutrophils was decreased, and the NF-κB signaling pathway was inhibited, indicating that vanillin suppressed the inflammatory response in the ectopic endometrium. Besides, we found that the intensity of tissue reactive oxygen species (ROS) was significantly lower, and mitochondrial complex IV expression was reduced in the vanillin-treated group. Meanwhile, treatment of the immortalized human endometriotic epithelial cell line (11Z) with vanillin resulted in the downregulation of cyclin genes that drive the cell proliferation process, inhibited cell proliferation, promoted apoptosis, and downregulated the expression of LPS-induced inflammatory cytokines. Most importantly, our data showed that the vanillin treatment had only minimal effects on the eutopic endometrium with respect to the pregnancy process, indicating its safety to be used in treating endometriosis in adults. In conclusion, our data suggest that vanillin has potential therapeutic properties for endometriosis as a regulatory molecule of cell proliferation, apoptosis, inflammation, and oxidative stress.
子宫内膜异位症是一种雌激素依赖性的慢性炎症性妇科疾病，其特征是子宫内膜腺体和基质位于子宫腔外，被称为异位内膜。最近的研究表明，子宫内膜异位症与激素失衡、炎症和氧化应激有关。香草醛是香草豆提取物的主要成分，作为一种调味剂广泛应用于食品、制药和化妆品行业。它具有抗炎、抗菌和抗肿瘤特性，但尚未研究其在子宫内膜异位症中的治疗效果。在这项研究中，我们使用诱导子宫内膜异位症的小鼠模型评估了香草醛在这种疾病中的作用。结果表明，香草醛显著抑制子宫内膜病变的生长。与对照组相比，香草醛治疗组的病变重量和体积明显减小，表明其抑制细胞增殖和促进细胞凋亡的能力很强。此外，在治疗组中，促炎细胞因子 、 、 、 的 mRNA 表达减少，巨噬细胞和中性粒细胞数量减少，NF-κB 信号通路受到抑制，表明香草醛抑制了异位内膜的炎症反应。此外，我们发现香草醛治疗组组织活性氧（ROS）的强度明显降低，线粒体复合物 IV 的表达减少。同时，香草醛处理永生化人子宫内膜异位上皮细胞系（11Z）导致驱动细胞增殖过程的细胞周期基因下调，抑制细胞增殖，促进细胞凋亡，并下调 LPS 诱导的炎症细胞因子的表达。最重要的是，我们的数据表明，香草醛治疗对妊娠过程中的在位子宫内膜只有很小的影响，表明其在治疗成人子宫内膜异位症方面具有安全性。总之，我们的数据表明，香草醛作为细胞增殖、凋亡、炎症和氧化应激的调节分子，具有治疗子宫内膜异位症的潜力。
