| Part I Syndrome Differentiation and Treatment of Diabetes by Ancient and ModernPhysiciansObjective:To analyze syndrome differentiation and treatment of diabetes by ancient and modern Chinese medicine physicians for future clinical reference.Methods:The understanding of diabetes by ancient and modern physicians was studied through reviewing representative works of all generations from academic origin, etiology, pathogenesis and treatment of the disease. Furthermore, pertinent medical records of renowned physicians about diabetes in ancient medical works found in Chinese Medical Bible, and in modern publications were analyzed from the aspect of evidence-based medicine. Ancient and modern databases of prescriptions used for the disease were established in Excel and analyzed with SPSS software. Descriptive analysis and hierarchical cluster analysis were conducted to reveal the regularity and characteristics of syndrome differentiation and treatment of diabetes in ancient and modern times in terms of classification, property, flavor and meridian tropism of the herbal medicines used. Based on the results, a vertical comparison was made to disclose the similarities and differences between experiences of modern renowned physicians and traditional ones.Results:The results show that reinforcing herbs and heat-clearing herbs are the two most commonly used medicines by ancient and modern physicians for diabetes, and within the former, Yin-nourishing and Qi-reinforcing herbs were predominant, which indicate that internal heat with insufficient Yin has been always considered as the basic pathogenesis of diabetes. Herbs for eliminating dampness and diuresis and astringent herbs are also widely used in all times, while herbs for promoting blood circulation to disperse stagnation are used more than the above two by modern physicians, indicating that while retention of phlegm and fluids retains its importance in diabetic pathogenesis, blood stagnation receives more attention in modern time. Herbs with cold property and herbs with sweet flavor are mostly used, accompanied by herbs with bitter flavor and spicy flavor, to clear heat to restore Yin, as well as to activate blood circulation. Analysis of meridian tropism shows that diabetes often affects multiple Zang and Fu organs. Lungs, stomach and kidney are three main organs in ancient time, which is in coordance with traditional principle of treatment according to three different positions;while liver, spleen and lung meridians are more often affected in modern treatment, emphasizing soothing the depressed liver and strengthening the spleen in transportation. Results from hierarchical cluster analysis show that reinforcing Qi to invigorate the spleen, nourishing Yin to moisten, clearing heat and balancing Yin and Yang in kidney are the major principles of treatment, cooresponding to syndromes of insufficience of Qi and Yin, excessive heat of Yangming, insufficient kidney Qi, insufficient Yin with internal heat and insuffient kidney Yin and kidney Yang. Above this, a group of herbs for activating Qi and blood circulation were found to be commonly used by modern physicians, indicating their attention on stagnation of liver, Qi and blood.Conclusion:This study revealed that, ancient and modern physicians agree with the basic pathogenesis of diabetes as internal heat with insufficient Yin, and the treatment principles of nourishing Yin, clearing heat and treatment in coordance with lungs, stomach and kidney, respectively. Yet above this, with further understanding of the disease, combinding knowledge of western medicine and clinical and experimental researches, modern physicians pay more attention to the liver and the spleen, pathogenesis of blood stagnation, and treatments of soothing the depressed liver, strengthening the spleen in transportation and promoting blood circulation to disperse stagnation.PartⅡEffects of Flavonoids of Guava Leaf on Insulin ResistanceObjective:To investigate the effects of several flavanoids of Guava Leaf, namely Genistein, Genistin and Formononetin, on insulin resistance and potential mechanisms.Methods:HepG2 cell line (Human hepatocellular liver carcinoma cell) was selected for the experiments. Cells were divided into 6 groups, normal control group, insulin resistance (IR) group, positive control (pioglitazone) group, Genistein group, Genistin group and Formononetin group, respectively. Except for normal control and IR groups, cells were pre-treated with 10μmol/L pioglitazone or 10μmol/L corresponding chemical for 24 hours, followed by a 16-hour treatment with the addition of palmitate (excluding normal control group), with a final palmitate and chemical concentration of 400μmol/L and10μmol/L. Then cellular fluorescent intensity of 2-NBDG was measured by flow cytometry for glucose uptake test; Western blotting was performed to measure protein expression level of Akt, phosphorylated Akt and PPARγ;and Real-time PCR for mRNA expression level of PPARγ.Results:In comparison with insulin resistance group, Genistein and Formononetin both can prevent decrease in glucose uptake rate in HepG2 cells induced by palmitate (P<0.01 and P<0.001), and the decrease in PPARy protein expression (P<0.05 and P<0.001). The two chemicals can also prevent palmitate-induced decrease in Akt phosphorylation (P<0.05 and P<0.01), as well as the decrease in PPAR-y mRNA expression (P<0.05 and P<0.001). Genistin was able to partially prevent plamitate-induced decrease in Akt phosphorylation (P<0.05), and to increase protein and mRNA expression levels of PPARy, but there was no statistical significance.Conclusion:Genistein and Formononetin can both prevent palmitate-induced insulin resistance and potentiate insulin action in cultured HepG2 cells. The mechanisms involve upregulating PPARy to stimulate glucose uptake, and protecting Akt phosphorylation to restore normal insulin signaling pathways.
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