Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, 100193, China.
J Ethnopharmacol. 2023 May 10;307:116214. doi: 10.1016/j.jep.2023.116214. Epub 2023 Feb 2.
Coreopsis tinctoria Nutt., a popular tea drink used in the Xinjiang region of China, has been traditionally used to treat diabetes and chronic metabolic diseases in China, Portugal, and North America. The bioactive extraction and potential mechanism have not been fully elucidated until now.
Traditional herbal medicines usually share network targets due to multicomponent therapeutics. Therefore, we tried to explore the protective effects of C. tinctoria on diabetes and the related molecular mechanism.
A flavonoid-rich fraction of C. tinctoria (CTF) was prepared. After 15 weeks of continuous treatment with CTF, the blood glucose and blood lipid levels of experimental mice were evaluated. Tissue was collected for differentially expressed genes (DEGs), bioinformatics analysis, RT‒PCR and Western blot for target-related DEGs.
After 15 weeks of continuous treatment with CTF, db/db mice showed reversed levels of glucose, insulin, glucagon and glycated hemoglobin A1c. CTF treatment also regulated total cholesterol, triglycerides, low density lipoprotein, nonesterified fatty acid, alanine transaminase, and aspartate transaminase. Major metabolic pathways were found to be dysregulated in the liver using a combined analysis of transcriptomics and network pharmacology. CTF treatment regulated 48.2% of 6357 dysregulated genes in db/db mice. The mitochondrial electron transport chain and tricarboxylic acid cycle were mainly affected. The sequencing data showed that fifty-nine predicted target genes for CTF were reverse regulated. Together with 1528 coexpressed genes, these genes reflected the main characteristics of the whole perturbed transcriptomic profile, i.e., dysregulated mitochondrial metabolism. The important genes of the target and coexpressed genes were further verified at the gene and protein levels.
The results confirm that the metabolic changes induced by hyperglycemia are closely related to mitochondrial metabolism in the liver. CTF alters a core gene set that exerts regulatory effects at the biological pathway level in db/db mice. In conclusion, our data reveal that an important molecular event for CTF treatment is the regulation of mitochondrial metabolism and support the idea that herbs or natural compounds are potential therapeutic substances for mitochondrial dysfunction-related diabetes.
金鸡菊 Nutt.，一种在中国新疆地区流行的茶饮，在中国、葡萄牙和北美地区传统上被用于治疗糖尿病和慢性代谢疾病。到目前为止，其生物活性提取和潜在机制尚未完全阐明。
传统草药通常由于多成分治疗而具有共享的网络靶点。因此，我们试图探索金鸡菊对糖尿病的保护作用及其相关的分子机制。
制备金鸡菊的富含类黄酮部分（CTF）。用 CTF 连续治疗 15 周后，评估实验小鼠的血糖和血脂水平。收集组织用于差异表达基因（DEGs）、生物信息学分析、RT-PCR 和 Western blot 检测与靶标相关的 DEGs。
用 CTF 连续治疗 15 周后，db/db 小鼠的血糖、胰岛素、胰高血糖素和糖化血红蛋白 A1c 水平得到逆转。CTF 治疗还调节了总胆固醇、甘油三酯、低密度脂蛋白、非酯化脂肪酸、丙氨酸转氨酶和天冬氨酸转氨酶。使用转录组学和网络药理学的联合分析，发现肝脏中的主要代谢途径失调。CTF 治疗调节了 db/db 小鼠中 6357 个失调基因的 48.2%。主要影响线粒体电子传递链和三羧酸循环。测序数据显示，CTF 的 59 个预测靶基因被反向调节。与 1528 个共表达基因一起，这些基因反映了整个扰动转录组谱的主要特征，即失调的线粒体代谢。靶基因和共表达基因的重要基因在基因和蛋白水平上进一步得到验证。
研究结果证实，高血糖引起的代谢变化与肝脏中线粒体代谢密切相关。CTF 改变了 db/db 小鼠中具有生物学途径水平调节作用的核心基因集。总之，我们的数据揭示了 CTF 治疗的一个重要分子事件是调节线粒体代谢，并支持草药或天然化合物是治疗与线粒体功能障碍相关的糖尿病的潜在治疗物质的观点。
