T2DM is an endocrine disease characterized by metabolic disorders and chronic complications, which is related to heredity, lifestyle, environment and other factors. The pathogenesis of T2DM is mainly related to insulin resistance (IR), islet β-cell dysfunction, inflammation and oxidative stress. Previous studies have shown that HJ, HQ, DH and other herbs have hypoglycemic effect . Polygonatum polysaccharide, the main active compound in HJ, reduces blood sugar by inhibiting the activity of α-glucosidase, and has anti-inflammatory, anti-tumor and improving immune function . Flavonoids from semen Astragali is the main extract of SYZ, which can enhance the antioxidant function of liver and improve the ability of tissue to scavenge free radicals, so as to relieve the damage of free radicals to islet β cells and promote the repair and regeneration of islet β cells, which help to achieve the role of regulating blood sugar . Active compounds in DH can improve glucose metabolism and β-cell function, regulate intestinal microflora, and reduce oxidative stress and inflammation. However, the specific mechanism of BJD in the antidiabetic process is not clear. Therefore, we used the method of network pharmacology to clarify the mechanism of the active components of BJD on type 2 diabetes. In the case of hyperglycemia, the body interferes with the mitochondrial electron transport chain, up-regulates the polyol pathway, increases the self-oxidation of glucose, promotes the production of free radicals, induces oxidative stress, damages islet β cells, and induces insulin resistance . There is a vicious circle among hyperglycemia, oxidative stress and diabetes . At the same time, some studies have reported that T2DM is a low-grade inflammatory disease, and the inflammatory response mediated by related inflammatory factors can lead to the occurrence and development of T2DM. These suggest that the occurrence and development of diabetes is closely related to oxidative stress and inflammatory reaction. On the other hand, the drugs developed with antioxidant and anti-inflammatory as the starting point have achieved satisfactory results in the treatment of T2DM alone or in combination with traditional hypoglycemic drugs [23–25], which further proves the broad prospect of antioxidant and anti-inflammatory therapy in the field of T2DM. The results of this study showed that (Fig. 2), quercetin, luteolin and kaempferol were identified as the active components related to the most targets, while the results of molecular docking (Table 1, Fig. 10) it is also confirmed that they have good binding properties to most target genes, suggesting that the above complexes may be the key components of BJD anti-T2DM. Quercetin is a flavonol compound which is widely distributed in nature and has a variety of biological activities. Quercetin is considered to be the most effective active oxygen (ROS) scavenger. Quercetin can not only improve lipid peroxidation, but also inhibit the production of several pro-inflammatory factors, such as tumor necrosis factor-α and carbon monoxide. At the same time, the antioxidant and anti-inflammatory effects of quercetin in T2DM treatment have been confirmed by various experiments in vivo and in vitro. Li  administered different doses of quercetin to diabetic rats and extracted the pancreas of diabetic rats. The study found that quercetin can effectively reduce the production of ROS in INS-1 cells and protect INS-1 cells from oxidative stress induced by high glucose. Moreover, quercetin reversed the expression of apoptotic proteins BAXm-RNA and PDX-1m-RNA and inhibited the apoptosis of INS-1 cells, which proved that quercetin could up-regulate the cell activity and insulin secretion of INS-1, and further improve blood glucose and glucose tolerance.
Luteolin, as a kind of natural weakly acidic tetrahydroxyflavonoids, has strong antioxidant and anti-inflammatory activities. In patients with T2DM, hyperglycemia down-regulates SIRTs-FOXO3a pathway and activates p47phox expression, and P47phox is necessary for ROS production . KIMA  study found that in T2DM patients, luteolin-treated group significantly down-regulated p47phox gene, reduced the production of ROS; this study further found that under the condition of hyperglycemia, human monocyte superoxide dismutase increased, but decreased to a normal level in the presence of luteolin, which suggests that luteolin inhibits the production of ROS by activating the expression of SIR and FOXO3a, to achieve the effect of prevention and treatment of diabetes. Kaempferol is also a natural flavonoid, and its anti-inflammatory, antioxidant and anticancer effects have been reported for the treatment of a variety of diseases, such as diabetes, obesity and cancer (such as liver, colon and skin cancer ). The above three compounds all have significant hypoglycemic effects on T2DM, and all have high oral availability (46.43%, 36.16%, 41.88%). They are considered to be representative compounds in BJD. As shown in Fig. 3, in order to obtain more accurate T2DM-related genes, we performed a series of parameters to screen the key goals in the PPI network, and finally identified 45 core goals, which may play an important role in the pathophysiological process of type 2 diabetes through direct or indirect action. Among them, the first five genes are MYC, TP53, APP, HSPB1 and EGFR. MYC is a highly pleiotropic transcription factor. It is conservatively estimated that 15% of all genes are directly regulated by MYC, including key roles in metabolism, cell cycle, differentiation and apoptosis. Increased expression of MYC protein can promote cell proliferation, however, this effect has been shown to be associated with a variety of human cancers . HofmannJW  studies have shown that MYC haploid deficiency (MYC+/-) mice have longer lifespan, higher metabolic rate and healthier fat metabolism, suggesting that the expression of MYC is not conducive to health. In T2DM machine, high glucose suppresses neurogenicdifferentiation1 (NEUROD1)-mediated insulin gene promoter by up-regulating the expression of MYC, thus affecting insulin gene transcription . Not only that, MYC is also an oxidative stress response gene [33 ~ 34], which is thought to be related to islet β-cell dedifferentiation . TP53 is one of the most closely related genes in human cancer. more and more evidence shows that it plays a regulatory role in diabetes, obesity and other fields , as well as in non-cancerous diseases (such as T2DM). P53 is activated in response to various injuries including oxidative stress, resulting in islet β-cell death. In addition, p53 affects glucose metabolism [37–40] and induces T2DM by directly regulating glucose uptake, glycolysis and gluconeogenesis. In recent years, progress has been made in the study of Amyloidprecursorprotein (APP) in peripheral organ diseases except Alzheimer's disease. AnYA  study shows that the increased expression of APP in whiteadiposetissue will lead to chain effects such as weight gain, impaired glucose tolerance and insulin resistance. HSPB1 is a member of the small molecular heat shock protein family, which is closely related to diabetes . The expression of HSPB1 is up-regulated under the action of cytokines and other cellular stressors to protect cells from oxidative stress, inflammation and apoptosis. It has been found that the islets of transgenic mice with high expression of HSPB1 are more resistant to β-cell apoptosis, indicating the correlation of HSPB1 in the protection of β-cells and islets . EGFR is involved in the proliferation, apoptosis and invasion of tumor cells. EGFR and its ligands play an important role in regulating the number of pancreatic β cells, especially islet β cells. Therefore, the above genes may become valuable clinical biomarkers and provide a new direction for the diagnosis and treatment of T2DM.
In BP, the common target of), BJD anti-T2DM is mainly concentrated in response to oxidative stress, cellular response to oxidative stress, response to lipopolysaccharide, regulation of angiogenesis, smooth muscle cell proliferation and so on. Oxidative stress is the pathological process of tissue and organ damage caused by the imbalance between oxidation and antioxidant systems in the body. it is the common soil that catalyzes the activation of protein kinase C, polyol bypass, the formation of terminal glycation products, inflammation and other pathological links . It is related to the occurrence and development of multi-system and chronic diseases such as diabetes, cardiovascular disease and so on. In recent years, it has been found that some antioxidant drugs, such as berberine, scavenge free radicals, inhibit the activation of polyol bypass and reduce the formation of terminal glycosylation products . To promote insulin secretion and improve insulin resistance . Therefore, BJD anti-T2DM may be related to antioxidation, and through antioxidation, regulation of angiogenesis and other ways to protect vascular endothelial function and prevent chronic complications of diabetes. In addition, BJD treatment of T2DM is also related to CC and MF, including mitochondria, endoplasmic reticulum, serine/threonineproteinkinasecomplex and cytokineactivity. Some studies have shown that there are ultrastructural abnormalities in the cells of patients with T2DM, such as endoplasmic reticulum dilation, mitochondrial swelling, cytoplasmic vacuolation, abnormal chromatin condensation and so on. In KEGG analysis, the first 20 KEGG pathways were screened, including Fluid shear stress and atherosclerosis, TNF signaling pathway, P13K-Akt signaling pathway, IL-17 signaling pathway and AGE-RAGE signaling pathway in diabetic complications, among which Fluid shear stress and atherosclerosis pathway was the most significant. In T2DM, insulin is the main ligand that regulates the metabolism of PI3K/AKT pathway. On the one hand, PI3KAkt signaling pathway increases glucose utilization and reduces gluconeogenesis in liver and muscle by activating glucose metabolism pathway; on the other hand, P13K/AKT-mediated growth factor signal plays an important role in glucose, lipid and protein metabolism . Hyperglycemia, oxidative stress, polyol pathway and inflammation stimulate the production and modification of AGEs[55–56]. The combination of AGEs and RAGE increases the production of ROS, leading to the upregulation of inflammation, the induction of oxidative damage and changes in cell metabolism [57–59], while oxidative stress can further stimulate the production of AGE . The intervention of diabetes includes not only the control of blood sugar, but also the prevention and treatment of complications. Diabetic complications include retinopathy, neuropathy, nephropathy, atherosclerosis (macroangiopathy) and microangiopathy. There is evidence that vascular dysfunction (macroangiopathy and microangiopathy) is the basis of most chronic complications of diabetes . Hyperglycemia triggers vascular complications through the following different mechanisms: direct toxicity of glucose, increased production of free radicals, accumulation of advanced glycation end products, and redox disorders induced by sorbitol pathway [48–49]. Moreover, fluid shear stress also plays an important role in the development of diabetic angiopathy [50–52]. It can be seen that Fluid shear stress and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications play an important role in the occurrence and development of T2DM complications. In addition, it is generally believed that the occurrence of insulin resistance is a chronic inflammatory process, and the mechanism of IR is closely related to inflammation. Inflammatory factors can participate in insulin signaling pathway to interfere with other signal transduction, and can also interact with oxidative stress process to aggravate IR,. This study confirmed by KEGG analysis that BJD may also play an anti-T2DM role by regulating IL-17 signaling pathway to mediate inflammatory response.
In summary, this study shows that the mechanism of the treatment of T2DM is related to its antioxidation, anti-inflammation, regulation of metabolism and so on. Quercetin, luteolin and kaempferol in BJD can regulate most of the related indexes of T2DM; three key genes screened by PPI network (ITGA4, TP53, MYC) may provide new ideas for T2DM therapy; BJD may regulate anti-T2DM function through biological processes such as response to oxidative stress, cellular response to oxidative stress, response to lipopolysaccharide, regulation of angiogenesis, smooth muscle cell proliferation and so on. The above functions are mainly realized through Fluid shear stress and atherosclerosis, TNF signaling pathway, P13KAkt signaling pathway, IL-17 signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Because this study is based on the existing database information, there is a lack of experimental verification. Therefore, it is necessary to carry out follow-up experimental analysis to confirm the reliability of the results of this study.