The present study examined treatment pathways (the ordered sequence of medications that a patient is prescribed) for three chronic diseases (hypertension, type 2 diabetes, and depression), compared the pathways with recommendations from guidelines, discussed differences and standardization of medications in different medical institutions, explored population diversification and changes of clinical treatment, and provided clinical big data analysis-based data support for the development and study of drugs in China. In order to run the "Treatment Pathways in Chronic Disease" protocol in Chinese data sources,we have built a large data research and analysis platform for Chinese clinical medical data. Data sourced from the Clinical Data Repository (CDR) of the First Affiliated Hospital of Nanjing Medical University was extracted, transformed, and loaded into an observational medical outcomes partnership common data model (OMOP CDM) Ver. 5.0. Diagnosis and medication information for patients with hypertension, type 2 diabetes, and depression from 2005 to 2015 were extracted for observational research to obtain treatment pathways for the three diseases. The most common medications used to treat diabetes and hypertension were metformin and acarbose, respectively, at 28.5 and 20.9% as first-line medication. New drugs were emerging for depression; therefore, the favorite medication changed accordingly. Most patients with these three diseases had different treatment pathways from other patients with the same diseases. The proportions of monotherapy increased for the three diseases, especially in recent years. The recommendations presented in guidelines show some predominance. High-quality, effective guidelines incorporating domestic facts should be established to further guide medication and improve therapy at local hospitals. Medical institutions at all levels could improve the quality of medical services, and further standardize medications in the future. This research is the first application of the CDM model and OHDSI software in China, which were used to study, treatment pathways for three chronic diseases (hypertension, type 2 diabetes and depression), compare the pathways with recommendations from guidelines, discuss differences and standardization of medications in different medical institutions, demonstrate the urgent need for quality national guidelines, explores population diversification and changes of clinical treatment, and provide clinical big data analysis-based data support for the development and study of drugs in China.

Antrodia cinnamomea (AC), an edible Taiwanese mushroom, has been recognized as a valuable natural resource with vast biological and medicinal benefits. Recently, the hypoglycemic and anti-diabetic effects of AC were mentioned in several studies. However, no studies have investigated α-glucosidase inhibitors from AC fruiting bodies (ACFB) as they relate to type 2 diabetes (T2D) treatment. The purpose of this study was to gain evidence of potent α-glucosidase inhibitory effects, as well as isolate, identify and characterize the active compounds of ACFB. The MeOH extract of ACFB demonstrated potent α-glucosidase inhibitory activity, and possessed high pH stability (pH 2⁻11) and thermostable properties at 40⁻50 °C. Further purification led to the isolation of eight constituents from ACFB, identified as: 25S-antcin K (1), 25R-antcin K (2), dehydrosulphurenic acid (3), 25S-antcin I (4), 25S-antcin B (5), 25R-antcin B (6), dehydroeburicoic acid (7) and eburicoic acid (8). Notably, the ACFB extract and its identified compounds, except 1, 4, and 6 demonstrated a greater effect (EC50 = 0.025⁻0.21 mg/mL) than acarbose (EC50 = 0.278 mg/mL). As such, these active compounds were determined to be new potent mushroom α-glucosidase inhibitors. These active compounds were also identified on the HPLC fingerprints of ACFB.

A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity leading to efficient anti-diabetic agents. All synthesized compounds exhibited good inhibitory activity against yeast α-glucosidase (IC50 values in the range of 181.0-474.5 µM) even much more potent than standard drug acarbose (IC50 = 750.0). Among them, quinazolinone-1,2,3-triazoles possessing 4-bromobenzyl moiety connected to 1,2,3-triazole ring (10g and 10p) demonstrated the most potent inhibitory activity towards α-glucosidase. Compound 10g inhibited α-glucosidase in a competitive manner with Ki value of 117 µM. Furthermore, the binding modes of the most potent compounds 10g and 10p in the α-glucosidase active site was studied through in silico docking studies. Also, lack of cytotoxicity of compounds 10g and 10p was confirmed via MTT assay.

Five new acylated aminooligosaccharides (1⁻5), together with one known related analogue (6), were isolated from Streptomyces sp. HO1518. Their structure was identified by extensive spectroscopic analysis, including 1D and 2D NMR data and high resolution electrospray ionization mass spectrometry (HRESIMS), and by comparison with those reported in the literature. All of the new compounds showed more promising porcine pancreatic α-amylase (PPA) inhibitory activities than the clinical drug acarbose, indicating them as potential pharmaceutical drug leads toward type II diabetes.

A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models. All the tested compounds demonstrated excellent to moderate reduction in blood glucose levels. Three of the compounds (Tz21, Tz7 and Tz10) showed excellent anti-diabetic effect by reducing concentration of glucose to 157.15 ± 1.79 mg/dL, 154.39 ± 1.71 mg/dL, 167.36 ± 2.45 mg/dL, respectively better than the standard drug, pioglitazone, 178.32 ± 1.88 mg/dL. Moreover, three derivatives Tz21, Tz4 and Tz24 with IC50 values of 0.21 ± 0.01 µM, 9.03 ± 0.12 µM and 11.96 ± 0.40 µM respectively also showed better inhibitory activities on alpha-glucosidase even more than the standard acarbose (IC50 = 18.5 ± 0.20 µM), indicating Tz21 has the highest inhibitory effect among the seven tested derivatives. Prediction of Drug like properties using molinspiration online software suggests that all the synthesized compounds have potential of becoming the orally active molecules. Thus, these novel hybrids could serve as potential candidates to become leads for the development of new drugs eliciting anti-hyperglycemic effect orally.

Endophytic fungi, especially from mangrove plants, are rich source of secondary metabolites, which plays a major role in various pharmacological actions preferably in cancer and bacterial infections. To perceive its role in antidiabetic activity we isolated and tested the metabolites derived from a novel strain Alternaria longipes strain VITN14G obtained from mangrove plant Avicennia officinalis. The crude extract was analyzed for antidiabetic activity and subjected to column chromatography. The isolated fractions were screened in vitro for α-glucosidase and α-amylase inhibitory activities. The cytotoxicity of the isolated fractions was studied on L929 cell lines. Following which, the screened fraction 2 was allowed for structure elucidation using gas chromatography-mass spectrometry, one-dimensional, two-dimensional nuclear magnetic resonance spectroscopy, ultraviolet, and Fourier-transform infrared analysis. The binding energies of the isolated fraction 2 with glycolytic enzymes were calculated by molecular docking studies using AutoDock Vina. The isolated fraction 2 identified as 2,4,6-triphenylaniline, showed no significant difference in α-amylase inhibition rates and a significant difference of 10% in α-glucosidase inhibition rates than that of the standard drug acarbose. Further, the cytotoxicity assay of the isolated fraction 2 resulted in a cell viability of 73.96%. Supportingly, in silico studies showed 2,4,6-triphenylaniline to produce a stronger binding affinity toward the glycolytic enzyme targets. The compound 2,4,6-triphenylaniline isolated from A. longipes strain VITN14G exhibited satisfactory antidiabetic activity for type 2 diabetes in vitro, which will further be confirmed by in vivo studies. Successful outcome of the study will result in a natural substitute for existing synthetic antidiabetic drugs.

The hypoglycemic and hypolipidemic effects of samnamul were investigated. The α-glucosidase inhibitory activity of samnamul in vivo was determined in normal mice. Oral administration of samnamul extract (500 mg/kg) or acarbose (50 mg/kg) significantly reduced the postprandial glucose response. The effects of chronic consumption of samnamul on fasting hyperglycemia and dyslipidemia were determined in C57BL/6 J mice with diabetes mellitus induced by a high-fat/high-sucrose (HFHS) diet. Consumption of samnamul extract at 0.5% of the diet for 12 weeks decreased serum glucose, triglyceride, and cholesterol levels, the homeostasis model assessment for insulin resistance index, and activities of maltase and sucrase in the small intestine. These results suggest that samnamul had hypoglycemic and hypolipidemic effects in an animal model of type 2 diabetes and that the hypoglycemic effect occurred partly via the inhibition of α-glucosidase activity.