Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability

Crocetin is one of the major active constituents of saffron (Crocus sativus L.) which has a reputation for facilitating blood circulation and dispersing blood stasis in traditional Chinese medicine. However, there is little evidence showing the relationship between crocetin intake and the risk of gastrointestinal diseases such as colitis. In order to investigate the effect of crocetin on the regulation of intestinal barrier function and intestinal microbiota composition, mice were treated with crocetin after 3% dextran sulfate sodium (DSS) administration for one week. We found that crocetin intake at 10 mg/kg aggravated colitis in mice, showing increased weight loss and more serious histological abnormalities compared with the DSS group. The 16s rDNA sequencing analysis of the feces samples showed that mice treated with 10 mg/kg crocetin had lower species diversity and richness than those treated with DSS. At the genus level, a higher abundance of Akkermansia and Mediterraneibacter, and a lower abundance of Muribaculaceae, Dubosiella, Paramuribaculum, Parasutterella, Allobaculum, Duncaniella, Candidatus Stoquefichus, and Coriobacteriaceae UCG-002 were observed in the crocetin group. Untargeted metabolomic analyses revealed that crocetin reduced the levels of primary and secondary bile acids such as 12-ketodeoxycholic acid, 7-ketodeoxycholic acid, 3-sulfodeoxycholic acid, 6-ethylchenodeoxycholic acid, chenodeoxycholate, glycochenodeoxycholate-7-sulfate, glycocholate, and sulfolithocholic acid in the colon. In conclusion, crocetin intake disturbed intestinal homeostasis and prolonged recovery of colitis by promoting inflammation and altering gut microbiota composition and its metabolic products in mice. Our findings suggest that patients with gastrointestinal diseases such as inflammatory bowel disease should use crocetin with caution.     

西红花酸对晚期糖化终产物诱导内皮细胞晚期糖基化终产物受体表达的抑制作用

目的: 研究西红花酸对晚期糖基化终产物(AGE)诱导牛内皮细胞(BEC)中晚期糖基化终产物受体(RAGE)mRNA表达的抑制作用,并探讨其可能机制。方法: 不同浓度的西红花酸(1、0.1、0.01 μmol/L)预孵BEC细胞12h后,用AGE(100 mg/L)刺激细胞12h,RT-PCR法测定RAGEmRNA的表达水平;ELISA法测定细胞间黏附分子-1(ICAM-1)的表达;试剂盒分别检测胞外超氧阴离子和硫代巴比妥酸反应产物(TBARS)浓度;同时,还用2,7-二氯荧光素(DCFH)测定了胞内H2O2的浓度,并用罗丹明123(Rh123)荧光法及MTT法分别检测细胞线粒体膜电位(MMP)水平和其琥珀酸脱氢酶(MSDH)的活性。结果: 与AGE模型组相比,西红花酸能显著抑制RAGEmRNA的表达(P<0.05),降低胞外超氧阴离子和TBARS(P<0.01或P<0.05)及胞内H2O2水平;结果还显示,西红花酸能提高细胞MMP水平和MSDH活性。对ICAM-1蛋白表达也有抑制作用,且呈时间和剂量依赖性。结论: 西红花酸可能通过清除AGE与RAGE结合产生的活性氧(ROS)来抑制RAGEmRNA的高表达。提示西红花酸对糖尿病血管病变有潜在的治疗价值。     

用Wittig和Wittig-Horner反应合成藏红花酸二甲酯

以短碳链化合物1,4-二溴-2-丁烯、丙酮醛缩二甲醇、2-溴丙酸甲酯和氯乙醛为起始原料,首先分别合成2,7-二甲基-2,4,6-辛三烯-1,8-二醛和γ-氯代惕各酸甲酯,然后将两者结合而成藏红花酸二甲酯。合成过程中碳碳双键的形成为关键步骤。通过比较Wittig和Wittig-Horner反应在双键形成中的作用,得出结论:合成2,7-二甲基-2,4,6-辛三烯-1,8-二醛时,宜用Wittig-Horner反应,产率为58.7%;合成γ-氯代惕各酸甲酯和藏红花酸二甲酯时,宜用Wittig反应,产率分别为74.3%和78.6%。