iridoids and Sleep-Initiation-and-Maintenance-Disorders

Alzheimer's disease (AD) is the leading cause of dementia and cognitive function impairment. The multi-faced character of AD requires new drug solutions based on substances that incorporate a wide range of activities. Antioxidants, AChE/BChE inhibitors, BACE1, or anti-amyloid platelet aggregation substances are most desirable because they improve cognition with minimal side effects. Plant secondary metabolites, used in traditional medicine and pharmacy, are promising. Among these are the monoterpenes-low-molecular compounds with anti-inflammatory, antioxidant, enzyme inhibitory, analgesic, sedative, as well as other biological properties. The presented review focuses on the pathophysiology of AD and a selected group of anti-neurodegenerative monoterpenes and monoterpenoids for which possible mechanisms of action have been explained. The main body of the article focuses on monoterpenes that have shown improved memory and learning, anxiolytic and sleep-regulating effects as determined by in vitro and in silico tests-followed by validation in in vivo models.

Topics: Acetylcholine; Acetylcholinesterase; Alzheimer Disease; Animals; Anti-Anxiety Agents; Anti-Inflammatory Agents; Antioxidants; Apolipoproteins E; Cholinesterase Inhibitors; Computer Simulation; Drug Evaluation, Preclinical; Encephalitis; Humans; Iridoids; Learning; Memory; Mice; Models, Molecular; Monoterpenes; Nerve Tissue Proteins; Neuroprotective Agents; Nootropic Agents; Oxidative Stress; Phytotherapy; Polyphenols; Protein Conformation; Rats; Sleep Initiation and Maintenance Disorders

The authors studied the sleep of patients with insomnia who complained of poor sleep despite chronic use of benzodiazepines (BZDs). The sample consisted of 19 patients (mean age 43.3+/-10.6 years) with primary insomnia (DSM-IV), who had taken BZDs nightly, for 7.1+/-5.4 years. The control group was composed of 18 healthy individuals (mean age 37+/-8 years). Sleep electroencephalogram (EEG) of the patients was analyzed with period amplitude analysis (PAA) and associated algorithms, during chronic BZD use (Night 1), and after 15 days of a valerian placebo trial (initiated after washout of BZD, Night 2). Sleep of control subjects was monitored in parallel.. Valerian subjects reported significantly better subjective sleep quality than placebo ones, after BZD withdrawal, despite the presence of a few side effects. However, some of the differences found in sleep structure between Night 1 and Night 2 in both the valerian and placebo groups may be due to the sleep recovery process after BZD washout. Example of this are: the decrease in Sleep Stage 2 and in sigma count; the increase in slow-wave sleep (SWS), and delta count, which were found to be altered by BZD ingestion. There was a significant decrease in wake time after sleep onset (WASO) in valerian subjects when compared to placebo subjects; results were similar to normal controls. Nonetheless, valerian-treated patients also presented longer sleep latency and increased alpha count in SWS than control subjects.. The decrease in WASO associated with the mild anxiolytic effect of valerian appeared to be the major contributor to subjective sleep quality improvement found after 2-week of treatment in insomniacs who had withdrawn from BDZs. Despite subjective improvement, sleep data showed that valerian did not produce faster sleep onset; the increase in alpha count compared with normal controls may point to residual hyperarousabilty, which is known to play a role in insomnia. Nonetheless, we lack data on the extent to which a sedative drug can improve alpha sleep EEG. Thus, the authors suggest that valerian had a positive effect on withdrawal from BDZ use.

Topics: Adult; Analysis of Variance; Benzodiazepines; Double-Blind Method; Electroencephalography; Female; Humans; Iridoids; Male; Middle Aged; Phytotherapy; Plant Roots; Sleep; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Valerian

Valerian root contains two substances of special pharmacological interest--valepotriates and sesquiterpenes. The former, which has been used for standardization of the drug, is cytotoxic. The latter has no such effect. Both have sedative effects. A double blind test has been carried out on a preparation (VALERINA NATT) containing primarily sesquiterpenes. When compared with placebo it showed a good and significant effect on poor sleep (p less than 0.001). Forty-four percent reported perfect sleep and 89% reported improved sleep from the preparation. No side effects were observed.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Drug Compounding; Female; Humans; Iridoids; Male; Middle Aged; Plant Extracts; Plants, Medicinal; Pyrans; Sesquiterpenes; Sleep; Sleep Initiation and Maintenance Disorders; Valerian

(1) Insomnia should be treated first with non drug measures; this has traditionally involved the use of herbal remedies. (2) About 20 plants are approved in France in the production of medications 'traditionally used' for minor sleep disturbances. Virtually nothing is known of their efficacy or potential dangers. (3) Most of these plants are suspected of toxicity and should therefore be avoided, especially in view of their unproven efficacy. (4) Littleleaf linden, vervain, melissa and orange flower have no demonstrated efficacy but are safe and can therefore be used. Similarly, there are no scientific grounds for rejecting preparations based on hawthorn or passiflora. (5) Available data suggest that valerian extracts have a modest impact on subjective sleep quality; they are nevertheless more effective than a placebo. Valerian products that do not contain valepotriates have no apparent adverse effects. It is best to avoid high-titre alcoholic extracts and powdered valerian root, and to select aqueous extracts and low-titre hydro-alcoholic preparations.

Topics: Anemone; Ballota; Benzodiazepines; Beverages; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Crataegus; Herbal Medicine; Humans; Humulus; Iridoids; Melissa; Passiflora; Phytotherapy; Plant Preparations; Sleep Initiation and Maintenance Disorders; Tilia; Valerian; Verbena