Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction.

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or α4ß2 nicotinic acetylcholine receptor (nAChR). This study provides practitioners a new insight of analgesic effects.

Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism In Vivo.

Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2 O2 -induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.

[Comparison of activated carbon and ultrafiltration technique in the production process of huoxue tongluo injection].

OBJECTIVE: To research the applicability of activated carbon and ultrafiltration technique in the production process of Huoxue Tongluo Injection. METHODS: The kinetic-turbidimetric method was used to determine the content of bacterial endotoxins in Huoxue Tongluo solution. Particle size change in Huoxue Tongluo solution was determined by nanometer particle size instrument before and after the use of different concentration activated carbon and different molecular weight ultrafiltration membrane. RESULTS: The removal efficacy of bacterial endotoxins was 65.2%, 77.5%, 80.4% by using three concentrations of active carbon at 0.05%, 0.10%, 0.30% in Huoxue Tongluo Injection, respectively. It was above 95% by using cutoff molecular weight both 5 kDa and 10 kDa ultrafiltration membrane. Measure results by nanometer particle size instrument showed that particle size of filter liquor by 10 kDa cutoff molecular weight ultrafiltration membrane was much smaller than that of by use of different concentration activated carbon. CONCLUSION: Ultrafiltration method is more suitable to the removal of bacterial endotoxins. The solution is more clear after using ultrafiltration method, and large particles of solution is removed. The ultrafiltration method provides the basis for injection production.