Enzymatic Synthesis and Evaluation of Eight Methylated Quercetin Products: In Vitro Chemical Properties and Adipogenesis Regulation
酶法合成和评估八种甲基化槲皮素产品:体外化学特性与脂肪生成调控
Authors: Beijun Ang, Tian Yang, Hongtao Jiang, Yong Cheng, Yang Chen, Xuejiao Qie, Liduan Yin, Tong Wang, Qiuming Chen, Zhaojun Wang, Maomao Zeng, Benu Adhikari, Zhiyong He, Jie Chen
Source: Journal of Agricultural And Food Chemistry
PMID: 40393977
Abstract
The methoxylated modification of flavonoids has been reported to enhance stability and permeability; however, its effect on the improvement of activity is not clear. In this study, Citrus depressa flavonoid O-methyltransferase 5 and Sorghum vulgare 7-O-methyltransferase were recombinantly expressed and successfully converted quercetin (QUE) into eight methoxylated products, which were isolated and identified with a purity exceeding 95%. All products except rhamnetin (RHA) showed improved stability, while only 5,7,3',4'-EMQ, 7,3',4'-TMQ, and 3,7,3',4'-EMQ had higher uptake ratios. Compared to QUE, 5,7,3',4'-EMQ and RHA significantly reduced the intracellular triglyceride level, while 3,5,7,3',4'-PMQ, 3,3',4'-TMQ and 3,7,3',4'-EMQ increased it. 5,7,3',4'-EMQ and RHA also significantly downregulated both the mRNA and protein levels of peroxisome proliferator-activated receptor γ, while 3,5,7,3',4'-PMQ and 3,7,3',4'-EMQ upregulated PPARγ at the transcriptional level to about ten times higher than that of QUE. The structure-activity relationship analysis highlighted the importance of C3-OH retention and dual methoxylation of the A-ring. In summary, this study efficiently produced eight structurally well-defined QUE methoxylation products via biotransformation, established an in vitro initial structure-activity relationship for regulating adipogenesis, and provided a potential structure for PPARγ regulation, a central target of lipid metabolism.
Keywords: PPARγ; lipid metabolism; methoxylation biotransformation; quercetin; structure-activity relationship.
摘要
据报道,对黄酮类化合物进行甲氧基化修饰可增强其稳定性和渗透性,但其对提高活性的影响尚不清楚。本研究重组表达了柑橘类黄酮 O-甲基转移酶 5 和高粱 7-O-甲基转移酶,成功地将槲皮素(QUE)转化为 8 种甲氧基化产物,并分离鉴定出纯度超过 95% 的产物。除鼠李素(RHA)外,所有产物的稳定性都有所提高,只有 5,7,3',4'-EMQ、7,3',4'-TMQ 和 3,7,3',4'-EMQ 的吸收比更高。与 QUE 相比,5,7,3',4'-EMQ 和RHA能显著降低细胞内甘油三酯的水平,而 3,5,7,3',4'-PMQ、3,3',4'-TMQ 和 3,7,3',4'-EMQ 则能增加细胞内甘油三酯的水平。5,7,3',4'-EMQ和RHA还能显著下调过氧化物酶体增殖激活受体γ的mRNA和蛋白质水平,而3,5,7,3',4'-PMQ和3,7,3',4'-EMQ则能在转录水平上上调PPARγ,上调幅度约为QUE的10倍。结构-活性关系分析强调了 C3-OH 保留和 A 环双甲氧基化的重要性。总之,本研究通过生物转化高效地制备了8种结构明确的QUE甲氧基化产物,建立了调控脂肪生成的体外初始结构-活性关系,并为脂质代谢的中心靶点PPARγ的调控提供了潜在的结构。
关键词: PPARγ;脂质代谢;甲氧基化生物转化;槲皮素;结构-活性关系。
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