[Discussion on efficacy evaluation thought and method for innovation medicine of Chinese herbal compound formula based on clinical application characteristics].

The Chinese herbal compound formula preparation was made based on theory of Chinese medicine, which was confirmed by long period clinical application, and with multi-compound and multi-target characteristics. During the exploitation process of innovation medicine of Chinese herbal compound formula, selecting and speeding up the research development of drugs with clinical value shall be paid more attention, and as request of rules involved in new drug research and development, the whole process management should be carried out, including project evaluation, manufacturing process determination, establishment of quality control standards, evaluation for pharmacological and toxic effect, as well as new drug application process. This reviews was aimed to give some proposals for pharmacodynamics research methods involved in exploration of Chinese herbal compound formula preparation, including： ①the endpoint criteria should meet the clinical attribution of new drugs; ②the pre-clinical pharmacodynamics evaluation should be carried on appropriate animal models according to the characteristics of diagnosis and therapy of Chinese medicine and observation indexes; ③during the innovation of drug for infants and children, information on drug action conforming to physiological characteristics of infants and children should be supplied, and the pharmacodynamics and toxicology research shall be conducted in immature rats according to the body weight of children. In a summary, the clinical application characteristics are the important criteria for evaluation of pharmacological effect of innovation medicine of Chinese herbal compound formula.

[Toxicity of mineral Chinese medicines containing mercury element].

Mineral Chinese medicine is the distinctive part of the Chinese traditional medicine. The mineral Chinese medicines containing mercury elements such as cinnabaris, calomelas and hydrargyri oxydum rubrum are widely applied in the clinical conditions because of their efficacy of sedative, sterilization, removing necrotic tissue and promoting granulation. However, the rationality and security of clinical application are questioned because of the toxic effect caused by mercury compounds. This paper would summarize the efficacy of the mineral Chinese medicines containing mercury element, as well as their hepatotoxicity, nephrotoxicity, embryotoxicity, and neurotoxicity effect and mechanisms. Improper usage or high dose of the mineral Chinese medicines containing mercury element would cause acute hepatotoxicity. Cinnabaris, calomelas and hydrargyri oxydum rubrum may lead to chronic hepatotoxicity, nephrotoxicity, embryotoxicity and neurotoxicity when they were applied externally to the skin for long-term use. In addition to the accumulation of mercury elements in the tissues and organs, the species and forms of mercury compounds absorbed into the body in different ways, should be also studied in order to understand the toxicity of the mineral Chinese medicines containing mercury element. Meanwhile the dose and period of treatment shall be also considered in order to provide the references for rational and safe clinical application of the mineral Chinese medicines containing mercury element.

Effects of Berberine on Adipose Tissues and Kidney Function in 3T3-L1 Cells and Spontaneously Hypertensive Rats.

We aimed to investigate the effect of berberine on adipose tissues, as well as its effect on renal injury in 3T3-L1 cells and spontaneously hypertensive rats. 3T3-L1 cells were cultured and treated with berberine (5-20 pM) from days 3 to 8. Berberine added to the cultured medium could significantly down-regulate transcription factors, including CCAAT/enhancer binding protein ß, CCAAT/enhancer binding protein a, and peroxisome pro liferator-activated receptor y, and suppress peroxisome proliferator-activated receptor target genes, such as adipocyte fatty acid binding protein and fatty acid synthase, and inhibit 3T3-Ll fibroblast differentiation to adipocytes. Male spontaneously hypertensive rats received either 150 mg/day of berberine or saline orally for 8 weeks. Compared with the control, berberine-treated rats exhibited significant reductions in body weight gain (p < 0.05), as well as retroperitoneal and mesenteric adipose tissues (p < 0.05). Berberine-treated rats significantly decreased urinary albumin excretion, a marker of renal injury (p < 0.05). Long-term treatment with berberine decreased the adipose tissues weight and attenuated renal injury in spontaneously hypertensive rats. Based on these results, berberine has an important role in regulating adipose tissues. These results suggest the protective effect of berberine on metabolic syndrome related diseases, such as renal injury.

Increased Oxidative Stress in Cultured 3T3-L1 Cells was Attenuated by Berberine Treatment.

The 3T3-L1 cell line is one of the most well-characterized and reliable models for studying adipocytes. Increased oxidative stress in accumulated fat was found in 3T3-L1 cells. Berberine, an isoquinoline alkaloid, could suppress fat deposition in 3T3-L1 cells; however, whether berberine suppresses increased oxidative stress is not well known. In this study, we observed the effect of berberine on increased oxidative stress in 3T3-L1 cells. 3T3-L1 cells were cultured and treated with berberine (5-20 µM) from day 3 to day 8. We confirmed that berberine markedly inhibited fat accumulation and lipid droplets in 3T3-L1 adipocytes and decreased triglyceride content. Berberine inhibited increased oxidative stress in 3T3-L1 cells by suppressing reactive oxygen species (ROS) production, and increased glutathione peroxidase (GPx) gene expression and GPx activity. Berberine also markedly reduced adipokines secreted by adipocytes, including leptin and resistin.

Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats.

The positive effects of berberine (30 mg/kg/day, i.g. for 6 weeks) on cardiac dysfunction were evaluated in the rat model of hyperglycemia and hypercholesterolemia. Hyperglycemia and hypercholesterolemia were induced by feeding high-sucrose/fat diet (HSFD) consisting of 20% sucrose, 10% lard, 2.5% cholesterol, 1% bile salt for 12 weeks and streptozotocin (30 mg/kg, i.p.). The plasma sugar, total cholesterol, and triglyceride levels were significantly increased (422, 194 and 82%, respectively) in the HSFD/streptozotocin-treated rats, when compared with control animals receiving normal diet and vehicle. Berberine treatment reduced the plasma sugar and lipid levels by 24-69% in the rat model of hyperglycemia and hypercholesterolemia. Cardiac functions signed as values of cardiac output, left ventricular systolic pressure, the maximum rate of myocardial contraction (+dp/dtmax), left ventricular end diastolic pressure and the maximum rate of myocardial diastole (-dp/dtmax) were injured by 16-55% in the hyperglycemic/hypercholesterolemic rats. Berberine increased cardiac output, left ventricular systolic pressure and +dp/dtmax by 64, 16 and 79%, but decreased left ventricular end diastolic pressure and -dp/dtmax by 121 and 61% in the rats receiving HSFD/streptozotocin, respectively, when compared with the drug-untreated rats of hyperglycemia and hypercholesterolemia. Berberine caused significant increase in cardiac fatty acid transport protein-1 (159%), fatty acid transport proteins (56%), fatty acid beta-oxidase (52%), as well as glucose transporter-4 and peroxisome proliferator-activated receptor-γ (PPARγ), but decrease in PPARα mRNA and protein expression in hyperglycemic/hypercholesterolemic rats. These results indicated that berberine exerted protective effects on cardiac dysfunction induced by hyperglycemia/hypercholesterolemia through alleviating cardiac lipid accumulation and promoting glucose transport.