Study on the Mechanism of Dendrobium officinale in Improving Glucose Metabolism

Type 2 Diabetes Mellitus (T2DM) is a chronic disease threatening human health, with hyperglycemia being its primary hallmark. The management of T2DM primarily relies on lifestyle interventions and lifelong medication. However, current antidiabetic drugs have limited efficacy and can cause various side effects, such as hypoglycemia, liver injury, and gastrointestinal reactions [1]. Therefore, identifying natural antidiabetic compounds with comparable efficacy and fewer side effects has emerged as a research focus.In Traditional Chinese Medicine (TCM), diabetes is referred to as "Xiaoke," with its fundamental pathomechanism involving Yin deficiency and internal heat. Dendrobium officinale (Dendrobium) possesses properties that nourish Yin, generate body fluids, nourish the stomach, and clear internal heat. Its primary active ingredients include polysaccharides, alkaloids, amino acids, trace elements, bibenzyls, phenanthrenes, and flavonoids [15], which can regulate the gut microbiota and exhibit hypoglycemic effects, aligning with the TCM principle of treating Xiaoke by addressing Yin deficiency and internal heat. Studies have shown that Dendrobium officinale can significantly reduce blood glucose levels in diabetic animal models, yet the precise mechanisms underlying its glucose metabolism improvement remain unclear. Tree shrews exhibit similarities to non-human primates and humans in terms of body weight, fasting blood glucose levels, gender, and age relationships [3], making them ideal experimental animals for diabetes research.The gut microbiota is closely related to hepatic glucose metabolism [2]. Current proposed mechanisms linking gut microbiota dysbiosis to T2DM include the short-chain fatty acid hypothesis, bile acid hypothesis, endotoxin hypothesis, and growth factor hypothesis. Short-chain fatty acids (SCFAs) are produced by the gut microbiota through the fermentation of undigested dietary fiber, starch, and carbohydrates. The gut microbiota is also intimately linked to hepatic glucose metabolism. The liver serves as a crucial target organ for insulin action and a major source of endogenous glucose production, playing a pivotal role in glucose production and output during fasting, as well as glucose absorption, utilization, and storage post-feeding. Hepatic insulin resistance leads to impaired glucose output, primarily due to abnormalities in hepatic insulin signaling pathways, increased gluconeogenesis, and glycogenolysis, resulting in elevated hepatic glucose output, thereby disrupting glucose metabolism and altering the gut microbiota.This study employs network pharmacology to analyze the multi-target components of Dendrobium and constructs a multi-target component network combined with the T2DM phenotype in tree shrews, an ideal experimental model. By validating the theoretical and practical consistency of Dendrobium in treating diabetes with reduced side effects compared to traditional drugs, we aim to elucidate the molecular mechanisms underlying its targeting of ADH1B and AKT genes to activate insulin signaling pathways, improve glucose metabolism from multiple aspects, alter the gut microbiota, and protect hepatic tissue, thereby providing a novel theoretical basis for treating glucose metabolism disorders in diabetic tree shrews.