The balanced homeostasis of the G protein–coupled receptor (GPCR), rhodopsin (Rho), is required for vision. Misfolding mutations in Rho cause photoreceptor death, leading to retinitis pigmentosa (RP) and consequently blindness. With no cure currently available, the development of efficient therapy for RP is an urgent need. Pharmacological supplementation with molecular chaperones, including flavonoids, improves stability, folding, and membrane targeting of the RP Rho mutants in vitro. Thus, we hypothesized that flavonoids by binding to P23H Rho and enhancing its conformational stability could mitigate detrimental effects of this mutation on retinal health. In this work, we evaluated the pharmacological potential of two model flavonoids, quercetin and myricetin, by using in silico, in vitro, and in vivo models of P23H Rho. Our computational analysis showed that quercetin could interact within the orthosteric binding pocket of P23H Rho and shift the conformation of its N‐terminal loop toward the wild type (WT)‐like state. Quercetin added to the NIH‐3T3 cells stably expressing P23H Rho increased the stability of this receptor and improved its function. Systemic administration of quercetin to P23H Rho knock‐in mice substantially improved retinal morphology and function, which was associated with an increase in levels of Rho and cone opsins. In addition, treatment with quercetin resulted in downregulation of the UPR signaling and oxidative stress‐related markers. This study unravels the pharmacological potential of quercetin to slow down the progression of photoreceptor death in Rho‐related RP and highlights its prospective as a lead compound to develop a novel therapeutic remedy to counter RP pathology.

The aim of the study was to explain the effects of sesquiterpene lactones (SLs) from chicory (Cichorium intybus L.) root extracts as inhibitors of acetylcholinesterase (AChE) at the molecular level and to determine the inhibition of AChE activity by specific SLs (lactucin and lactucopicrin) and different chicory extracts. The obtained SLs-rich extracts were purified by the countercurrent partition chromatography (CPC) technique. AChE inhibitors were analyzed using two models: isothermal titration calorimetry (ITC) and docking simulation. The results of ITC analysis of the enzyme and the ligands’ complexation showed strong interactions of SLs as well as extracts from chicory with AChE. In a test of enzyme activity inhibition after introducing acetylcholine into the model system with SL, a stronger ability to inhibit the hydrolysis of the neurotransmitter was observed for lactucopicrin, which is one of the dominant SLs in chicory. The inhibition of enzyme activity was more efficient in the case of extracts, containing different enzyme ligands, exhibiting complementary patterns of binding the AChE active site. The study showed the high potential of using chicory to decrease the symptoms of Alzheimer’s disease.

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Butyrylcholinesterase (BChE) is a major enzyme from the alpha-glycoprotein family that catalyzes the hydrolysis of neurotransmitter acetylcholine (ACh), lowering the concentration of ACh in the nervous system, which could cause aggravation of Alzheimer’s disease (AD). In select pathological conditions, it is beneficial to reduce the activity of this enzyme. The aim of this study was to evaluate the degree of BChE inhibition by coffee extracts fractionated into mono- and diesters of caffeic acid/caffeine, digested in vitro in the gastrointestinal tract. The bioactive compounds from coffee showed high affinity for BchE, −30.23–−15.28 kJ/mol, and was the highest for the caffeine fraction from the green Arabica extract. The isolated fractions were highly effective in inhibiting BChE activity at all in vitro digestion phases. It has been shown that the fractionation of coffee extracts could be potentially used to obtain high prophylactic or even therapeutic effectiveness against AD.