为了进一步阐明白茶中主要化合物对血糖的影响,采用网络药理学对白茶中8个主要化合物与糖尿病进行关联分析,并采用斑马鱼生物模型进行验证。网络药理学分析显示,白茶中没食子酸、儿茶素组分（C、EC、ECG、EGC、EGCG、GCG）及咖啡碱主要通过TNF、p53、SRC、CASP3等4个靶点调节血糖。斑马鱼模型验证结果显示,斑马鱼对不同样品的最大耐受浓度（LC0）各不相同,白茶茶汤为100.00 µg·mL-1,没食子酸、咖啡碱为6.25 µg·mL-1,EGCG为12.50 µg·mL-1,ECG、EGC、GCG为25.00 µg·mL-1,EC为50.00 µg·mL-1,C为150.00 µg·mL-1;在LC0下,与模型组相比,阳性药物组、白茶茶汤组、没食子酸组、EGCG组、ECG组、EGC组、GCG组、EC组、C组的血糖值分别下降53.7%、16.2%、33.6%、47.3%、30.0%、52.6%、25.8%、21.5%、29.4%,均表现出显著降血糖作用（P<0.05）;咖啡碱组血糖值升高16.9%,呈现显著升血糖作用（P<0.05）。实时荧光定量PCR结果显示,与空白组相比,模型组的TNF、SRC和CASP3的表达量显著升高,TP53的表达量显著降低（P<0.05）;与模型组相比,没食子酸及儿茶素组分组的TNF、SRC和CASP3的表达量显著降低（P<0.05）,TP53的表达量显著升高（P<0.05）;咖啡碱组的TNF和SRC的表达量显著升高（P<0.05）,TP53和CASP3表达量无显著差异。结果表明,白茶中没食子酸及儿茶素组分均具显著降血糖作用,主要通过调节TNF、p53、SRC和CASP3 4个靶点发挥作用,咖啡碱具有显著升血糖作用,主要通过TNF和SRC靶点发挥作用。
To further clarify the effects of the main compounds in white tea on blood glucose levels, the network pharmacology was used to conduct a correlation analysis between 8 main compounds in white tea and diabetes, and a zebrafish biological model was adopted for verification. The network pharmacology analysis reveals that blood glucose was primarily regulated by gallic acid, catechin group, and caffeine in white tea through four targets: TNF, p53, SRC and CASP3. The verification results of the zebrafish model show that the maximum tolerance concentrations of zebrafish to the different samples were as follows: 100.00 µg·mL-1 (white tea soup), 6.25 µg·mL-1 (gallic acid, caffeine), 12.50 µg·mL-1 (EGCG), 25.00 µg·mL-1 (ECG, EGC, GCG), 50.00 µg·mL-1 (EC), and 150.00 µg·mL-1 (C). At this concentration, the blood glucose values decreased significantly in all groups compared with the model group: the positive drug (ACA) group by 53.7%, the white tea soup group by 16.2%, the gallic acid group by 33.6%, the EGCG group by 47.3%, the ECG group by 30.0%, the EGC group by 52.6%, the GCG group by 25.8%, the EC group by 21.5%, and the C group by 29.4%. Only the caffeine group showed a significant blood glucose-elevating effect (P<0.05), with an increase of 16.9%. The qPCR results show that, compared with the blank group, the expression levels of TNF, SRC and CASP3 in the model group were significantly increased, while the expression level of TP53 was significantly decreased (P<0.05). Compared with the model group, the expression levels of TNF, SRC and CASP3 in the gallic acid and catechin groups were significantly decreased (P<0.05), while the expression level of TP53 was significantly increased (P<0.05). The expression levels of TNF and SRC in the caffeine group were significantly increased (P<0.05), while there were no significant differences in TP53 and CASP3. The results show that gallic acid and catechin components in white tea both exhibited significant hypoglycemic effects, which were mainly achieved by regulating four targets: TNF, p53, SRC and CASP3. In contrast, caffeine was found to have a significant blood glucose-elevating effect, primarily through TNF and SRC.
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