Abstract
The hypoglycemic decoction (HD) is a traditional Chinese medicine (TCM) preparation for the treatment of diabetes mellitus (DM), with a remarkable therapeutic effect. However, its mechanism of action is still unclear at the metabolic level. In this study, the biochemical markers from type 2 DM (T2DM) rats, induced by a high-sugar and high-fat diet combined with streptozotocin (STZ), were detected. The metabolomics-based analysis using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was conducted to evaluate urine samples from control, model, metformin, and HD groups. After oral administration of HD for 28 days, the general state, weight, fasting blood glucose (FBG), blood lipid level, oral glucose tolerance test (OGTT), fasting insulin (FINS), insulin sensitivity index (ISI), and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly improved (P < 0.01). The western blotting showed that HD can enhance the protein expression of glucose transporter 4 (GLUT4) and adenosine monophosphate-activated protein kinase (AMPK). The metabolomics results revealed that after treatment with HD, the levels of L-carnitine, 1-methyladenosine, 1-methylhistamine, and 3-indoleacrylic acid were upregulated and the levels of riboflavin, phenylalanine, atrolactic acid, 2-oxoglutarate, citrate, isocitrate, cortisol, and glucose were downregulated. The main mechanism may be closely related to the regulation of the tricarboxylic acid (TCA) cycle, phenylalanine metabolism, glyoxylate metabolism, and dicarboxylate metabolism. Additionally, it was also found that HD can regulate the protein expression of GLUT4 and AMPK to interfere with TCA cycle and carbohydrate metabolism to treat T2DM.
Highlights
Diabetes mellitus (DM) is a complex and serious metabolic disease associated with abnormally high levels of blood glucose attributed to defective insulin secretion or action [1]
According to Traditional Chinese medicine (TCM), the occurrence of DM is related to deficiency of spleen and stomach qi and fire excess from yin deficiency. e TCM hypoglycemic decoction (HD) contains Astragalus propinquus, Pueraria, Rhizoma polygonati, Atractylodis Rhizoma, Salvia miltiorrhiza, Radix Scrophulariae, Rhizoma Dioscoreae, mulberry leaves, Polygonatum odoratum, and Bombyx batryticatus
The serum levels of total cholesterol (TC), TG, and low-density lipoprotein cholesterol (LDL-C) in the metformin and HD groups were significantly lower than those in the model group (P < 0.01), and the high-density lipoprotein cholesterol (HDL-C) level significantly increased (P < 0.01), indicating that HD acts by regulating the blood lipid levels
Summary
Diabetes mellitus (DM) is a complex and serious metabolic disease associated with abnormally high levels of blood glucose attributed to defective insulin secretion or action [1]. The global incidence of DM has increased each year as a consequence of lifestyle changes, population aging, and urbanization, which lead to a series of cardiovascular diseases. It is estimated that by 2035, the number of patients with DM will reach to 600 million, and the incidence of DM in China will increase to 143 million and rank first in the world [3]. According to the International Diabetes Federation, the current yearly cost of DM in China is $25 billion and this cost may continue to increase to over $47 billion in 2030 [4, 5]. According to TCM, the occurrence of DM is related to deficiency of spleen and stomach qi and fire excess from yin deficiency. To further verify and explore the mechanism of HD in regulating glycometabolism, the specific experiment scheme of this study was designed as follows
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