Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, China.
Chem Biodivers. 2023 May;20(5):e202201047. doi: 10.1002/cbdv.202201047. Epub 2023 May 3.
Phenylpropionamides in the seed of Cannabis sativa L. (PHS) have a protective effect on neuroinflammation and antioxidant activity. In this study, the UHPLC-Orbitrap-fusion-TMS-based metabolomics approach was used to analyze the serum samples and identify potential biomarkers in Streptozotocin (STZ) induced Alzheimer's disease (AD) rats. The results revealed that primary bile acid biosynthesis and taurine and hypotaurine metabolism were significantly correlated with STZ-induced AD rats. In addition, the key enzymes in these two pathways were verified at the protein level. The levels of cysteine dioxygenase type I (CDO1), cysteine sulfinic acid decarboxylase (CSAD), cysteamine (2-aminoethanethiol) dioxygenase (ADO), 7α-hydroxylase (CYP7A1), and sterol 12α-hydroxylase (CYP8B1) were the key enzymes affecting the two pathways in AD rats compared with the control group (CON). Furthermore, after a high-dose group of phenylpropionamides in the seed of Cannabis sativa L. (PHS-H) was administrated, the levels of CDO1, CSAD, CYP7A1, and CYP8B1 were all callback. These findings demonstrate for the first time that the anti-AD effect of PHS is associated with the regulation of primary bile acid biosynthesis and taurine and hypotaurine metabolism in STZ-induced AD rats.
大麻种子中的苯丙酰胺(PHS)对神经炎症和抗氧化活性具有保护作用。在这项研究中,我们采用 UHPLC-Orbitrap-融合-TMS 代谢组学方法分析了链脲佐菌素(STZ)诱导的阿尔茨海默病(AD)大鼠的血清样本,并鉴定出潜在的生物标志物。结果表明,初级胆汁酸生物合成和牛磺酸及次牛磺酸代谢与 STZ 诱导的 AD 大鼠显著相关。此外,在蛋白质水平上验证了这两条途径中的关键酶。与对照组(CON)相比,AD 大鼠中胱氨酸双加氧酶 I 型(CDO1)、半胱氨酸亚磺酸脱羧酶(CSAD)、半胱胺(2-氨基乙硫醇)双加氧酶(ADO)、7α-羟化酶(CYP7A1)和甾醇 12α-羟化酶(CYP8B1)等关键酶的水平影响着两条途径。此外,在大麻种子中的苯丙酰胺(PHS)高剂量组给药后,CDO1、CSAD、CYP7A1 和 CYP8B1 的水平均回调。这些发现首次表明,PHS 的抗 AD 作用与 STZ 诱导的 AD 大鼠中初级胆汁酸生物合成和牛磺酸及次牛磺酸代谢的调节有关。