Jia Qiang, Qi Yuchen, Li Hanbo, Ding Hai, Qi Dongmei, Li Yunlun
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Jinan 250355, China.
Evid Based Complement Alternat Med. 2023 Jan 31;2023:2139634. doi: 10.1155/2023/2139634. eCollection 2023.
Radish seed (RS), the dried ripe seed of L., is widely used in traditional Chinese medicine (TCM) to reduce blood pressure. However, the molecular and pharmacological mechanisms underlying its therapeutic effects are still unclear. In this study, we analyzed the effects of RS in a rat model of prehypertension and assessed the mechanistic basis by integrating transcriptomics and metabolomics. RS administration significantly reduced blood pressure in prehypertensive male Wistar rats, negatively regulated endothelin-1, increased nitric oxide levels, and reduced the exfoliation of endothelium cells. In vitro vascular ring experiments further confirmed the effects of RS on vascular endothelial cells. Furthermore, we identified 65 differentially expressed genes (DEGs; < 0.05 and fold change (FC) > 2) and 52 metabolites (VIP > 1, < 0.05 and FC ≥ 2 or ≤0.5) in the RS intervention group using RNA-seq and UPLC-MS/MS, respectively. A network of the DEGs and the metabolites was constructed,q which indicated that RS regulates purine metabolism, linoleic acid metabolism, arachidonic acid metabolism, circadian rhythm, and phosphatidylinositol signaling pathway, and its target genes are Pik3c2a, Hspa8, Dnaja1, Arntl, Ugt1a1, Dbp, Rasd1, and Aldh1a3. Thus, the antihypertensive effects of RS can be attributed to its ability to improve vascular endothelial dysfunction by targeting multiple genes and pathways. Our findings provide new insights into the pathological mechanisms underlying prehypertension, along with novel targets for the prevention and treatment of hypertension.
莱菔子(RS),即十字花科植物萝卜的干燥成熟种子,在传统中药中被广泛用于降低血压。然而,其治疗效果背后的分子和药理机制仍不清楚。在本研究中,我们分析了莱菔子在高血压前期大鼠模型中的作用,并通过整合转录组学和代谢组学评估其作用机制。给予莱菔子可显著降低高血压前期雄性Wistar大鼠的血压,负调控内皮素-1,增加一氧化氮水平,并减少内皮细胞脱落。体外血管环实验进一步证实了莱菔子对血管内皮细胞的作用。此外,我们分别使用RNA测序和超高效液相色谱-串联质谱法在莱菔子干预组中鉴定出65个差异表达基因(DEGs;P < 0.05且折叠变化(FC)> 2)和52种代谢物(VIP > 1,P < 0.05且FC≥2或≤0.5)。构建了DEGs和代谢物的网络,表明莱菔子调节嘌呤代谢、亚油酸代谢、花生四烯酸代谢、昼夜节律和磷脂酰肌醇信号通路,其靶基因是Pik3c2a、Hspa8、Dnaja1、Arntl、Ugt1a1、Dbp、Rasd1和Aldh1a3。因此,莱菔子的降压作用可归因于其通过靶向多个基因和通路改善血管内皮功能障碍的能力。我们的研究结果为高血压前期的病理机制提供了新的见解,同时也为高血压的预防和治疗提供了新的靶点。