piperidines and ferulic-acid

Ferulic acid (FA) acts as a powerful antioxidant against various age-related diseases. To investigate the effect and underlying mechanism of FA against d-galactose(d-gal)-induced memory deficit, mice were injected with d-gal to induce memory impairment and simultaneously treated with FA and donepezil. The behavioral results revealed that chronic FA treatment reversed d-gal-induced memory impairment. Further, FA treatment inhibited d-gal-induced AChE activity and oxidative stress via increase of superoxide dismutase activity and reduced glutathione content, as well as decrease of malondialdehyde and nitric oxide levels. We also observed that FA significantly inhibits inflammation in the brain through reduction of NF-κB and IL-1β by enzyme-linked immunosorbent assay. Additionally, FA treatment significantly reduces the caspase-3 level in the hippocampus of d-gal-treated mice. Hematoxylin and eosin and Nissl staining showed that FA prevents neurodegeneration induced by d-gal. These findings showed that FA inhibits d-gal-induced AChE activity, oxidative stress, neuroinflammation and neurodegeneration, and consequently ameliorates memory impairment.

Topics: Acetylcholinesterase; Aging; Animals; Antioxidants; Brain; Caspase 3; Coumaric Acids; Disease Models, Animal; Donepezil; Galactose; Glutathione; Hippocampus; Indans; Interleukin-1beta; Male; Malondialdehyde; Memory Disorders; Mice; NF-kappa B; Nitric Oxide; Oxidative Stress; Piperidines; Superoxide Dismutase

Due to the complex nature of Alzheimer's disease, there is a renewed and growing search for multitarget drugs.. Donepezil-ferulic acid hybrids (DFAHs) were prepared by the one-pot Ugi-4CR in low-to-moderate yields. DFAHs are potent antioxidant agents, showing oxygen radical absorbance capacity values in the range 4.80-8.71 trolox equivalents, quite higher compared with those recorded for ferulic acid and melatonin. From the ChEs inhibition studies, we conclude that DFAH 8, bearing an ethylene linker, and DFAH 12, bearing a propylene linker, both substituted with a melatonin motif, are the most potent inhibitors, in the nanomolar range.. We have identified DFAH 8 as a very potent antioxidant, and totally selective equineButyrylCholinEsterase (eqBuChE) inhibitor.

Topics: Alzheimer Disease; Antioxidants; Butyrylcholinesterase; Cholinesterase Inhibitors; Coumaric Acids; Donepezil; Humans; Indans; Piperidines

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.

Topics: Alkaloids; Animals; Antidepressive Agents; Benzodioxoles; Biogenic Monoamines; Biological Availability; Brain Chemistry; Coumaric Acids; Depression; Drug Synergism; Hindlimb Suspension; Male; Mice; Mice, Inbred ICR; Monoamine Oxidase; Motor Activity; Neurotransmitter Agents; Piperidines; Polyunsaturated Alkamides; Swimming