A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction: "Focus" mode of integrated biomarkers.

It is difficult to accurately evaluate the efficacy of traditional Chinese medicine (TCM), which leads to the uncertainty and complexity of dose-effect analysis. In this study we established the "Focus" mode of biomarkers to characterize the dose-effect relationship of Gegen Qinlian Decoction (GQD), a TCM formula for treating type 2 diabetes mellitus (2-DM). A rat model of 2-DM was established through high fat diet feeding combined with low-dose STZ injection. Rats with 2-DM were administered high, middle or low doses (6.785, 4.071, 1.357 mg·kg-1·d-1, respectively) of GQD extract for 60 d. Metformin (300 mg·kg-1·d-1) was taken as the positive control. Blood samples were collected to assess serum biochemical indexes and metabolic profiling. After "Focus" analysis, the biochemical index triglycerides (TG) and insulin sensitivity (ISI) were identified as focused integrated biomarkers (FIBs), while arachidonic acid and docosatetraenoic acid were the metabolic FIBs. Dose-effect relationship curves of GQD were built based on these types of FIBs. Furthermore, the two dose-effect relationship curves showed similar trends with the middle dosage displaying the greatest efficacy, suggesting that insulin function and arachidonic acid metabolism played important roles in 2-DM and the responses to GQD. The metabolic FIB docosatetraenoic should be further explored for understanding its involvement in the process of 2-DM occurrence and the treatment. This "Focus" mode provides a novel strategy to evaluate the dose-effect relationship of a TCM. The system and concepts established here may also be applicable for assessing the dose-effect relationships of Western medicines.

[Therapeutic effects of gegen qinlian decoction and its mechanism of action on type 2 diabetic rats].

The objective of this study is to fully investigate the therapeutic effect and mechanisms of action of Gegen Qinlian decoction (GD) on type 2 diabetes mellitus (type 2 DM). A rat model of type 2 DM was established with the combination of high-fat diet and multiple low doses of streptozotocin (STZ). Biochemical indicators related to glucose metabolism disorders, insulin resistance, oxidative stress were observed. The type 2 DM rats were administrated with GD for 80 days, the above-mentioned indexes were detected. The results indicated that the hepatic glycogen synthesis level was promoted, fasting blood glucose level and fasting blood insulin level were significantly reduced, insulin sensitivity index was significantly improved; the level of superoxide dismutase (SOD) was increased and the level of malondialdehyde (MDA) was reduced; pathologic morphology of pancreas and kidney was ameliorated in the GD group. It was indicated that the therapeutic mechanisms of action of GD on type 2 DM might be related to its effect of ameliorating glucose metabolism disorders, relieving insulin resistance, increasing the tissues' sensitivity to insulin, improving the antioxidative ability of living system, GD has therapeutic effect on type 2 DM and protective effects against damaged pancreatic function.

An "Umpolung Relay" Strategy: One-Pot, Twice Polarity Inversion Cascade Synthesis of Diversified [60]Fulleroindoles.

An "umpolung relay" strategy, which includes an one-pot, twice polarity inversion cascade of C60 via carbanion and carbocation polarity reversed relay pathway, has been developed for the synthesis of a diverse range of novel [60]fulleroindole derivatives.