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Scutellarin (1) possesses protective effects against neuronal injury, while 6-O-methyl-scutellarein (3), as the main metabolite of scutellarin in vivo, has not been reported about its protective effects previously. The present study mainly investigated whether the neural injury caused by ischemia/reperfusion would be influenced by different doses of 6-O-methyl-scutellarein (3). The results of behavioral, neurological, and histological examinations indicated that 6-O-methyl-scutellarein (3) could improve neuronal injury, and exhibit significant difference among the various doses. More importantly, 6-O-methyl-scutellarein (3) had better protective effects than scutellarin in rat cerebral ischemia. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a neurodegenerative disorder, which is complex and progressive; it has not only threatened the health of elderly people, but also burdened the whole social medical and health system. The available therapy for AD is limited and the efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the design and development of efficacious and safe anti-AD agents has become a hotspot in the field of pharmaceutical research. Due to the multifactorial etiology of AD, the multitarget-directed ligands (MTDLs) approach is promising in search for new drugs for AD. Tacrine, which is the first acetylcholinesterase (AChE) inhibitor, has been selected as the ideal active fragment because of its simple structure, clear activity, and its superiority in the structural modification, thus it could be introduced into the overall molecular skeletons of the multi-target-directed anti-AD agents. In this review, we have summarized the recent advances (2012 to the present) in the chemical modification of tacrine, which could provide the reference for the further study of novel multi-target-directed tacrine derivatives to treat AD. [ABSTRACT FROM PUBLISHER]

ContextScutellarin (1) has been widely used in China to treat acute cerebral infarction and paralysis induced by cerebrovascular diseases. However, scutellarin (1) has unstable metabolic characteristics. ObjectiveThe metabolic profile of 6-O-scutellarein was studied to determine its metabolic stabilityin vivo. Materials and methodsIn this study, a method of UFLC/Q-TOF MS was used to study the 6-O-methyl-scutellarein metabolites in rat plasma, urine, bile and faeces after oral administration of 6-O-methyl-scutellarein (3). One hour after oral administration of 6-O-methyl-scutellarein (3) (34 mg/kg), approximately 1 mL blood samples were collected in EP tubes from all groups. Bile, urine and faeces samples were collected from eight SD rats during 0–24 h after oral administration. The mass defect filtering, dynamic background subtraction and information dependent acquisition techniques were also used to identify the 6-O-methyl-scutellarein metabolites. ResultsThe parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces. The glucuronide conjugate of 6-O-methyl-scutellarein (M1,M2), diglucuronide conjugate of 6-O-methyl-scutellarein (M3), sulphate conjugate of 6-O-methyl-scutellarein (M4), glucuronide and sulphate conjugate of 6-O-methyl-scutellarein (M5), methylated conjugate of 6-O-methyl-scutellarein (M6) were detected in rat urine.M1,M2andM3were detected in rat bile.M1was found in rat plasma andM7was detected in faeces. Discussion and conclusionBecause the parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces, we speculate that 6-O-methyl-scutellarein (3) had good metabolic stabilityin vivo.This warrants further study to develop it as a promising candidate for the treatment of ischemic cerebrovascular disease. [ABSTRACT FROM PUBLISHER]

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 H2O2-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. [ABSTRACT FROM AUTHOR]

The binding abilities of scutellarin (Scu) and scutellarein (Scue) with bovine serum albumin (BSA) were investigated using equilibrium dialysis, high performance liquid chromatography, fluorescence spectroscopy, competitive site marker and molecular docking. The results showed that the average protein binding ratios of Scu and Scue with BSA were (79.85 ± 1.83) and (85.49 ± 1.21) % respectively. Under simulated physiological conditions, the fluorescence data indicated that Scu and Scue bound with BSA through a static mechanism. The thermodynamic parameters indicated that the interactions of Scu-BSA and Scue-BSA mainly occurred by van der Waals forces and hydrogen bonds and it was easier for Scue to bind with BSA than Scu, indicating that the glucuronic acid molecule in Scu decreased the binding affinity. Site competitive marker experiments showed that the binding sites of Scu and Scue mainly located within the sub-domain IIA of BSA. Furthermore, molecular docking studies indicated that one BSA could bind three Scue, while one BSA could carry only two Scu. All these results clearly indicated the interactions of Scu and Scue with BSA, which will lay the foundation for further research to determine the pharmacology and pharmacodynamics of Scu and Scue for treating ischemic cerebrovascular disease. [ABSTRACT FROM AUTHOR]

Scutellarin, which is extracted from the dried plant of Erigeron breviscapus, has been reported to protect the neural injury against excitotoxicity induced by ischemia. However, there are a few studies on the protective effects of scutellarein, which is the main metabolite of scutellarin in vivo. Thus, this study investigated the neuroprotective effects of scutellarein on cerebral ischemia/reperfusion in rats by bilateral common carotid artery occlusion (BCCAO) model, through the analysis of endogenous amino acids using HILIC-MS/MS, and evaluation of Ca2+ concentration together with Ca2+-ATPase activity. The results showed that scutellarein having good protective effects on cerebral ischemia/reperfusion might by decreasing the excitatory amino acids, increasing the inhibitory amino acids, lowing intracellular Ca2+ level, and improving Ca2+-ATPase activity, which suggested that scutellarein might be a promising potent agent for the therapy of ischemic cerebrovascular disease. [ABSTRACT FROM AUTHOR]

An improved synthesis of 6-O-methyl-scutellarein is described. Benzyl bromide was selected to protect both the hydroxyl groups at C-4' and C-7 in scutellarein. The product was then methylated and deprotected to produce the target compound in high yield in four steps. [ABSTRACT FROM AUTHOR]