Abstract
BackgroundDiabetes is a serious chronic metabolic disorder. Trichosanthes kirilowii Maxim. (TK) is traditionally used for the treatment of diabetes in traditional Chinese medicine (TCM). However, the clinical application of TK on diabetic patients and the hypoglycemic efficacies of TK are still unclear.MethodsA retrospective cohort study was conducted to analyze the usage of Chinese herbs in patients with type 2 diabetes in Taiwan. Glucose tolerance test was performed to analyze the hypoglycemic effect of TK. Proteomic approach was performed to identify the protein constituents of TK. Insulin receptor (IR) kinase activity assay and glucose tolerance tests in diabetic mice were further used to elucidate the hypoglycemic mechanisms and efficacies of TK.ResultsBy a retrospective cohort study, we found that TK was the most frequently used Chinese medicinal herb in type 2 diabetic patients in Taiwan. Oral administration of aqueous extract of TK displayed hypoglycemic effects in a dose-dependent manner in mice. An abundant novel TK protein (TKP) was further identified by proteomic approach. TKP interacted with IR by docking analysis and activated the kinase activity of IR. In addition, TKP enhanced the clearance of glucose in diabetic mice in a dose-dependent manner.ConclusionsIn conclusion, this study applied a bed-to-bench approach to elucidate the hypoglycemic efficacies and mechanisms of TK on clinical usage. In addition, we newly identified a hypoglycemic protein TKP from TK. Our findings might provide a reasonable explanation of TK on the treatment of diabetes in TCM.
Highlights
Diabetes is a serious chronic metabolic disorder
Evidence-cased Chinese medicinal herbs commonly used in diabetic patients in Taiwan We conducted a retrospective cohort study to analyze the Chinese medicinal herbs commonly used among diabetic patients
By analyzing the LHID 2000, we found that 70,093 patients (15.83%) with endocrine, nutritional and metabolic diseases, and immunity disorders had treated with Trichosanthes kirilowii Maxim. (TK)
Summary
Prescription pattern of TCM on diabetic patients in National Health Insurance system A retrospective study was conducted using registration and claim datasets of the year 2002 from National Health Insurance Research Database (NHIRD), which covers claims of ambulatory care, inpatient services, dental services, and prescriptions from 99% of the overall population in Taiwan. To induce type 1 diabetes, C57BL/6J mice were injected daily with 50 mg/kg STZ by an intraperitoneal route for five consecutive days. Mice were starved overnight and TKE or TKP were orally given 15 min before intraperitoneally injection of glucose solution (4 g/kg for normal mice and 1 g/kg for diabetic mice). Trichloroacetic acid-precipitated protein samples (200 μg) were applied to IPG strips (7 cm, pH 3-10). Mixtures containing IR (Sigma, St. Louis, MO, USA) and various amounts of insulin or TKP in kinase buffer (25 mM HEPES, pH 7.6, 25 mM MgCl2, 100 μM ATP, 100 μM sodium orthovanadate, 2.5 mg/mL poly(Glu,Tyr), 25 μCi/mL [γ-32P]ATP) were incubated at 30 °C for 10 min and spotted on chromatography papers. A p value less than 0.05 was considered as statistical significance
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