Dose-toxicity-effect relationship between licorice combined with rhubarb in purgation / 中国中药杂志

The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.

Therapeutic window analysis of Tripterygium wilfordii processed by liquorice: an instantiation using allergic contact dermatitis / 中国中药杂志

The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.

Network analysis and mechanism prediction of “effectiveness-toxicity” of liver injury in treatment of hepatitis with Xiaochaihu Decoction / 中草药

Objective: To explore the “efficacy-toxicity” targets, pathways, and mechanism of Xiaochaihu Decoction in the treatment of hepatitis based on the ADR information excavating of drug-induced liver injury in the treatment of hepatitis with Xiaochaihu Decoction. Methods: Taking Xiaochaihu Decoction as the research object, the integrated pharmacology platform was used to analyze and predict key targets and pathways. Cytoscape software was used to collate and analyze key targets and pathways to obtain co-participation pathways and mechanisms of “efficacy-toxicity”. Results: The analysis of the effect of Xiaochaihu Decoction for liver injury in the treatment of hepatitis showed that there were 40 common targets such as HADHA, HADH, NSDHL, ADH1A, ALDH 3A2, and GCK among the top 100 candidate targets with degree value. The chemical components jointly participated in the network of “effect-toxicity” which belonged to Xiaochaihu Decoction including 27 components in Bupleuri Radix, 74 components in Ginseng Radix, 13 components in Pinelliae Rhizoma, 8 components in Zingiberis Rhizoma, 32 components in Glycyrrhizae Radix et Rhizoma, 39 components in Jujubae Fructus, and 33 components in Scutellaria baicalensis. A total of 226 components were involved in the “effect-toxicity” process through endocrine and metabolic diseases, non-alcoholic fatty liver disease (NAFLD), estrogen signaling pathway, neurodegenerative diseases, nervous system, chemokine signaling pathway, and endocrine system. Conclusion: The “efficacy-toxicity” effect of Xiaochaihu Decoction on liver injury in the treatment of hepatitis may be closely related to Ras/Raf/MEK/ERK, NF-B, and PI3K/AKT signal transduction pathway. It plays a role by regulating cell proliferation, cell apoptosis and the expression of inflammatory factors, which provides a theoretical basis for further pharmacological and toxicological verification and chemical separation research. It plays a role by regulating cell proliferation, cell apoptosis and the expression of inflammatory factors.

Management and safety assessment of nanomaterials in food: status and prospects / 中华预防医学杂志

The safety assessment of nanomaterials in food is essential for safeguarding supervision and maintaining public health. However, there are still no safety assessment procedures for nanomaterials established in national-level in China and no specific toxicology and safety assessment procedures about nanomaterials for food, too. These factors lead to restriction on food safety protection and supervision. Current methods of evaluating the safety of nanomaterials mainly rely on traditional toxicological assessment that are extrapolated based on animal experiment from high doses to low doses and from animals to humans. These uncertainties restrict the accuracy of safety assessment for nanomaterials and also limit the development of scientific and effective evaluation procedures and regulatory measures. Currently, the key issues need to be solved including exposure assessment and evaluation methods of nanomaterials in food and the established methods of the toxicity test for nanomaterials that are consistent with the objectives of toxicity test in the 21st century vision and strategy. In this article, we reviewed current administrative regulatory, situations, and existing issues of food nanomaterials either in China or some developed countries in order to provide a scientific basis in establishing safety assessment procedures for nanomaterials in food in the future.

Methodology of toxicity-effect characterization of Chinese materia medica incompatibility based on disease and symptom conditions / 中草药

The incompatibility of Chinese materia medica (CMM) has always been one of the important scientific issues of CMM safety research. Extensive researches about CMM incompatibility have been carried out represented by "eighteen-antagonisms", mainly focused on the safety evaluation, toxic effects of substances, toxicology, toxicokinetics, drug interactions, toxicity mechanisms, etc. However, due to lack of system design on research ideas, model and methods, many key issues still lacked reliable conclusions, and did not reach a consensus within the industry. We completed the toxicity-effect characterization of the anti-drugs about "Pinelliae Rhizoma, Trichosanthis Fructus, Fritillariae Cirrhosae Bulbus, Ampelopsis Radix, and Bletillae Rhizoma attack Aconiti Radix" and proposed that the serious adverse reactions caused by related anti-drug combination therapy were because of the "toxicity" of CMM incompatibility. The formation of CMM incompatibility was closely related to its composition, dose, compatibility environment, etc, wherein the disease and symptom are the key factors of incompatibility. Eventually, the research model of toxicity-effect characterization of CMM incompatibility based on the desease and symptom was formed, it was viable to provide new strategies and methods for the clinical drug safety of CMM compatibility.