Dissection of the potential pharmacological function of neohesperidin dihydrochalcone – a food additive – by in vivo substances profiling and network pharmacology

Food additives are widely used in our daily life, and the side-effects caused by them have gained extensive attention around the world.

Anti-inflammatory effect of foods and crude drugs in relation to bitter and spicy tastes

Backround: In Kampo medicine as well as traditional Chinese medicine, each crude drug is classified by four properties (cold, cool, warm, and heat), five tastes (sour, bitter, sweet, spice, and salt) based on the Yin-yang and five elements (wood, fire, earth, metal, water) theory. The four properties and five tastes are greatly related to the medicinal efficacy of the crude drug in Kampo medicine. The pharmacological function of crude drugs is called "Yakuno" in Japanese. Examples of Yakuno include various functions such as clearing heat and removing blood stasis. Crude drugs with properties classified as cold or cool have the function to clear heat as they cool the body. Crude drugs classified as bBitter also have the function to clear heat. We speculated that anti-inflammatory constituents are included in crude drugs and food that are classified as cold or cool in property and bitter in taste.Keywords: crude drug, Kampo medicine, food, property, taste, nitric oxide, inflammation, pharmacological function

Effects of simvastatin and fenofibrate on butyrylcholinesterase activity in the brain, plasma, and liver of normolipidemic and hyperlipidemic rats

The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14–17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity.

Heterobiaryl synthesis by contractive C–C coupling via P(V) intermediates

Heterobiaryls composed of pyridine and diazine rings are key components of pharmaceuticals and are often central to pharmacological function. We present an alternative approach to metal-catalyzed cross-coupling to make heterobiaryls using contractive phosphorus C–C couplings, also termed phosphorus ligand coupling reactions. The process starts by regioselective phosphorus substitution of the C–H bonds para to nitrogen in two successive heterocycles; ligand coupling is then triggered via acidic alcohol solutions to form the heterobiaryl bond. Mechanistic studies imply that ligand coupling is an asynchronous process involving migration of one heterocycle to the ipso position of the other around a central pentacoordinate P(V) atom. The strategy can be applied to complex drug-like molecules containing multiple reactive sites and polar functional groups, and also enables convergent coupling of drug fragments and late-stage heteroarylation of pharmaceuticals.