No abstract

Okinawa propolis (OP) and its major ingredients were reported to have anti-cancer effects and lifespan-extending effects on Caenorhabditis elegans through inactivation of the oncogenic kinase, p21-activated kinase 1 (PAK1). Herein, five prenylated flavonoids from OP, nymphaeol-A (NA), nymphaeol-B (NB), nymphaeol-C (NC), isonymphaeol-B (INB), and 3′-geranyl-naringenin (GN), were evaluated for their anti-inflammatory, anti-diabetic, and anti-Alzheimer’s effects using in vitro techniques. They showed significant anti-inflammatory effects through inhibition of albumin denaturation (half maximal inhibitory concentration (IC50) values of 0.26–1.02 µM), nitrite accumulation (IC50 values of 2.4–7.0 µM), and cyclooxygenase-2 (COX-2) activity (IC50 values of 11.74–24.03 µM). They also strongly suppressed in vitro α-glucosidase enzyme activity with IC50 values of 3.77–5.66 µM. However, only INB and NA inhibited acetylcholinesterase significantly compared to the standard drug donepezil, with IC50 values of 7.23 and 7.77 µM, respectively. Molecular docking results indicated that OP compounds have good binding affinity to the α-glucosidase and acetylcholinesterase proteins, making non-bonded interactions with their active residues and surrounding allosteric residues. In addition, none of the compounds violated Lipinski’s rule of five and showed notable toxicity parameters. Density functional theory (DFT)-based global reactivity descriptors demonstrated their high reactive nature along with the kinetic stability. In conclusion, this combined study suggests that OP components might be beneficial in the treatment of inflammation, type 2 diabetes mellitus, and Alzheimer’s disease.

Prenatal exposure to excessive glucocorticoids alters the programming of the metabolic and endocrine balance of various organs, including the nervous system. In the present study, prenatal glucocorticoid treatment was shown to increase the susceptibility of the inner ear to acoustic noise trauma in adult life. Acute auditory brainstem response thresholds were not different between the age-matched groups. However, when measured at 48 h and 4 weeks postexposure, the dexamethasone (DEX)-treated rats showed little or no recovery from the trauma. In contrast, normal rats showed a significant amount of recovery by 48 h postexposure and continued to show further recovery over 4 weeks. In addition, acoustic trauma resulted in a massive outer hair cell loss in the DEX rats compared to minor loss in the normal rats. To determine whether oxidative stress plays a role in the recovery phase of acoustic trauma, the free radical scavenger PBN (100 mg/kg) was administered before, during and several times after noise exposure. PBN treatment significantly reduced the physiological and morphological cochlear differences which were observed between DEX and control rats after acoustic trauma. These data support the hypothesis that alterations in the intrauterine environment may modify the developmental programme of the cochlea, inducing dysfunction later in adult life. Excessive prenatal exposure to dexamethasone decreased the potential for recovery of the cochlea to oxidative stress induced by acoustic trauma; this decreased recovery potential can be counteracted by treatment with antioxidants.