Much emphasis has been placed on the biological activities of citrus peel's essential oils (CPEOs) against human ailments. This study investigated the effect of Citrus limon and Citrus reticulata peel's essential oils (EOs) on behavioral and neurochemical imbalance in transgenic and Harwish (Wild) fruit flies. Flies were divided into seven groups comprising of the control and those that were fed with 0.1, 0.5, and 1.0 µg/ ml of the dietary inclusions of study CPEOs for 7 days. Thereafter, behavioral profile was examined using lethality response and negative geotaxis assays. Effect of the EOs on cholinesterase and monoamine oxidase (MAO) activities, and antioxidative parameters were determined. The result showed a significant improvement of behavioral pattern and biochemical parameters of the flies fed with studied CPEOs inclusive diets. Conclusively, both EOs exert neuroprotective capability by reducing cholinesterases and monoamine activities, and also prevent oxidative stress, which are implicated in neuronal dysfunction in humans. Practical applications With the growing increase in the search for safer alternatives, having no side effects, for the management of neurodegenerative diseases, a large proportion of the populace is beginning to find solace in the use of natural products. Also, the wide array of similarities between the humans and the dipteran insects, fruit flies is a perfect organism for the study of neurodegenerative diseases. Therefore, this study presents the neuroprotective potentials of lemon and tangerine peels-derived EOs, and the possibility of their exploration as neuroactive agents and alternative in the management of Alzheimer's disease (AD).

The key to preventing mCRPC progression is understanding how androgen-dependent PCa cells progress to independence and modify their transcriptional repertoire accordingly. We recently identified a novel axis of the Hippo pathway characterized by the sequential kinase cascade induced by androgen deprivation, AR−>TLK1B>NEK1>pYAP1-Y407, leading to CRPC adaptation. Phosphorylation of YAP1-Y407 increases upon ADT or induction of DNA damage, correlated with the known increase in NEK1 expression/activity, and this is suppressed in the Y407F mutant. Dominant expression of YAP1-Y407F in Hek293 cells reprograms the YAP1-mediated transcriptome to reduce TEAD- and p73-regulated gene expression and mediates sensitivity to MMC. NEK1 haploinsufficient TRAMP mice display reduced YAP1 expression and, if castrated, fail to progress to overt prostate carcinomas, even while displaying reduced E-Cadherin (E-Cad) expression in hyperplastic ductules. YAP1 overexpression, but not the Y407F mutant, transforms LNCaP cells to androgen-independent growth with a mesenchymal morphology. Immunohistochemical examination of prostate cancer biopsies revealed that the pYAP1-Y407 nuclear signal is low in samples of low-grade cancer but elevated in high GS specimens. We also found that J54, a pharmacological inhibitor of the TLK1>NEK1>YAP1 nexus leading to degradation of YAP1, can suppress the transcriptional reprogramming of LNCaP cells to androgen-independent growth and EMT progression, even when YAP1-WT is overexpressed.

This study sought to determine the life span promoting effecof orange (Citrus sinensis), tangerine (Citrus maxima) and grapefruit (Citrus paradisi) peels in Drosophila melanogaster model. Flies (both gender, 3 to 5 days old) were divided into seven (7) groups (n = 5) containing 40 flies each; group I (control) flies were fed with basal diet, II-VII were flies were fed with basal diet containing 0.1 and 1.0% of tangerine peel (TP), orange peel (CP), and grapefruit peel (GP) respectively, for 14 days. Locomotor performance and memory index were assessed via negative geotaxis and aversive phototaxis suppression assays, respectively. Thereafter, the fly homogenates were assayed for activities of acetylcholinesterase (AChE), monoamine oxidase (MAO) and antioxidant enzymes as well as other indices of their redox. The results revealed that the citrus peels significantly improved longevity, locomotor performance, memory index, antioxidant status, and modulate cholinesterase and monoamine oxidase enzyme activities in treated flies when compared to the control. The results obtained suggest that the citrus peels offer potentials as dietary supplement with life span promoting properties in D. melanogaster model which could as well serve as a functional food additives. Practical applications Citrus peels, although often considered agro-wastes, are used as food supplements and food ingredents especially in production of candies, jams and custards. This study suggests the use of orange (Citrus sinensis), tangerine (Citrus maxima), and grapefruit (Citrus paradisi) peels as dietary supplements which offers potential life span promoting properties.

This research assessed the antioxidant activities and effects of some selected phenolic acids (ferulic, Caffeic, p-coumaric and chlorogenic acid) on enzymes of the purinergic signalling in isolated rat brain which include ATPdase, ecto- 51nucleotidase, phosphodiesterase and Na+/ K+ ATPase. Standard stock solutions (13mM) of the selected phenolics (Caffeic acid, ferulic acid, chlorogenic acid, p-coumaric acid) were prepared and several dilutions (0.05mM-10mM) were subsequently prepared; the ability of the phenolic acids to inhibit Fe2+ induced malondialdehyde (MDA) production in rat’s brain homogenates were assessed. Furthermore, the antioxidant activities of the phenolic acids as typified by the radicals (DPPH* and ABTS*) scavenging abilities were investigated. The results revealed that ferulic acid had the highest Na+/K+ -ATPase (IC50 =3.48 /ml) stimulatory activityas well as the highest ecto-5'-nucleotidase (IC50 =6.222 μg/ml) inhibitory activity while chlorogenic acid had the highest phosphodiesterase-51 (IC50 =21.03μg/ml) inhibitory activity and P-coumaric acid  had the highest inhibition of ATPDase (IC50 =17.56 μg/ml)  activity. Also, chlorogenic acid had the highest ABTS* and DPPH* scavenging abilities and also the strongest inhibition of Fe2+ induced MDA production in rat brain. However, this study revealed that the phenolic acids altered critical enzymes of the purinergic signaling and therefore suggests their possible neuromodulatory effect.

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