Lei Xue, Zhou Ziqian, Wang Sihong, Jin Li Hua
Department of Genetics, College of Life Sciences, Northeast Forestry University, Harbin, Heilongjiang Province, China.
Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian Province, China.
Toxicol Appl Pharmacol. 2022 Mar 15;439:115939. doi: 10.1016/j.taap.2022.115939. Epub 2022 Feb 23.
Drosophila is often exposed to harmful environments, and the intestinal epithelium is the first line of defense against external infection. Intestinal stem cells (ISCs) in the Drosophila midgut play a crucial role in maintaining tissue homeostasis and compensating for cell loss caused by tissue damage. Crocus sativus L. (saffron) can protect against intestinal injury in response to inflammation; however, the specific protective components of saffron and the related mechanisms remain unclear. Safranal is one of the main components of saffron. Here, we used dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15) to create an intestinal injury model and explored the protective effect of safranal against tissue damage. Excessive proliferation and differentiation of ISCs in the Drosophila midgut were observed after DSS or Ecc15 feeding; however, these phenotypes were rescued after safranal feeding. In addition, we found that this process occurred through inhibition of the c-Jun N-terminal kinase (JNK), epidermal growth factor receptor (EGFR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Furthermore, safranal inhibited the Ecc15- and DSS-induced increases in antimicrobial peptide (AMP) and reactive oxygen species (ROS) levels and intestinal epithelial cell death, thereby protecting gut integrity. In summary, safranal was found to have a significant protective effect and maintain intestinal homeostasis in Drosophila; these findings provide a foundation for the application of safranal in clinical research and the treatment of intestinal injury.
果蝇经常暴露于有害环境中，而肠道上皮是抵御外部感染的第一道防线。果蝇中肠的肠道干细胞（ISC）在维持组织稳态和补偿由组织损伤引起的细胞损失方面发挥着关键作用。藏红花（番红花）可以预防炎症引起的肠道损伤；然而，藏红花的具体保护成分及相关机制仍不清楚。藏红花醛是藏红花的主要成分之一。在此，我们使用葡聚糖硫酸钠（DSS）或胡萝卜软腐欧文氏菌胡萝卜软腐致病变种15（Ecc15）建立肠道损伤模型，探讨藏红花醛对组织损伤的保护作用。在喂食DSS或Ecc15后，观察到果蝇中肠ISC过度增殖和分化；然而，在喂食藏红花醛后，这些表型得到了挽救。此外，我们发现这个过程是通过抑制c-Jun氨基末端激酶（JNK）、表皮生长因子受体（EGFR）和Janus激酶（JAK）/信号转导和转录激活因子（STAT）途径发生的。此外，藏红花醛抑制了Ecc15和DSS诱导的抗菌肽（AMP）和活性氧（ROS）水平升高以及肠道上皮细胞死亡，从而保护肠道完整性。总之，发现藏红花醛对果蝇具有显著的保护作用并维持肠道稳态；这些发现为藏红花醛在临床研究和肠道损伤治疗中的应用提供了基础。
