RESUMO
To provide the basis for further development and research of drugs, non-clinical pharmacokinetics studies were conducted on HM475, which is composed of natural active molecules honokiol and metformin through cyclization. In this paper, HM475 was studied from six aspects by gavage and intraperitoneal injection: 1) Acute toxicity of HM475 in rats, 2) Pharmacokinetic characteristics of HM475 in rats, 3) Distribution characteristics of HM475 in heart, liver, spleen, lung, and kidney, small intestine, fat and brain of rats, 4) Main metabolic pathways of HM475 in rats, 5) Excretion of HM475 in rats, 6) Determination of protein binding rate of HM475 in bovine plasma, rabbit plasma, and rat plasma. Acute toxicity of HM475 on SD rats was evaluated by maximum dose method. The metabolic analysis method of HM475 in rats was first established by UPLC-Q-TOF-MS/MS technology, and the pharmacokinetic characteristics of oral administration and intraperitoneal injection were studied. Experimental results showed that HM475 had no obvious acute toxicity. The absolute oral bioavailability of HM475 was 38.45 %, and the drug concentration in plasma was higher than that in tissues. Combined with the process characteristics of HM475 in vivo, it is inferred that HM475 has enterohepatic circulation. In this study, non-clinical pharmacokinetics were systematically studied to provide data support for the clinical pharmacokinetics and pharmacodynamics of HM475, to more accurately predict the pharmacokinetic behavior of HM475 in human body and provide scientific data for the compound to enter clinical research.
Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Ratos , Animais , Bovinos , Humanos , Coelhos , Espectrometria de Massas em Tandem/métodos , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão/métodos , Compostos de Bifenilo , Administração OralRESUMO
The rhizoma of Anemarrhenae asphodeloides has a long history of hypoglycemic use in Chinese traditional medicine. In this article, 400â µmol/L H2 O2 induced normal INS-1 pancreatic beta cells to establish experimental model of oxidative damage. Quercetin was used as a positive drug, and mangiferin and its ethanolic extract were selected as therapeutic agents in an oxidative damage model to evaluate the ameliorative effect of the active ingredients of Anemarrhenae asphodeloides rhizoma on oxidative damage in INS-1 pancreatic ß-cells. Building a qualitative analysis method of membrane phospholipids of INS-1 pancreatic beta cells and identified 82 phospholipids based on the UPLC/Q-TOF MS technology, which could provide a database for further statistics analysis. OPLS-DA was used to screen the phospholipid biomarkers from the raw data. Exploring the biological significances of these biomarkers, and discussing the toxic effect of the effective components of Anemarrhena asphodeloides rhizoma, on oxidatively damaged INS-1 pancreatic beta cell.
Assuntos
Anemarrhena , Medicamentos de Ervas Chinesas , Células Secretoras de Insulina , Cromatografia Líquida de Alta Pressão/métodos , Rizoma , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
Based on the principle of molecular splicing and theory of traditional Chinese medicine pairs, a new multi-active compound (HM475) was synthesized by connecting metformin with honokiol, and its structure was characterized, which not only reduced the toxicity of raw materials, but also maintained the original activity, and had a certain significance in research and innovation. At the same time, quality control and preliminary activity evaluation were carried out, and the effect of HM475 on neuroinflammation was further explored, which provided a new idea for drug development of neurodegenerative diseases.