A review: Biological activity of myrtenal and some myrtenal-containing medicinal plant essential oils

Introduction: Myrtenal, a component of many plants` essential oils, is a bicyclic monoterpenoid. Numerous effects of myrtenal in experimental animals have been found - bronchodilatory, anti-inflammatory, anti-aggregative and antihemolytic (in vitro), and antibacterial.  Its other activities have been studied - antioxidant, antitumor, antihyperglycemic, vasodilating, heart rate reducing and hypotensive. Myrtenal is relatively little studied in the field of neuroscience.Aim: The aim of this article is to summarize the available information on the established biological activity of the monoterpenoid myrtenal.Materials and Methods: Scientific databases such as PubMed, ResearchGate, HMDB and others have been used to provide information on the published results of properties and activities of the test substance (myrtenal) over a period of 15 years (2003 - 2018).Results: Our research confirmed the available data for its central nervous system (CNS) activity - anxiolytic and potentiating the effects of the hypnotic drugs, as well as the antioxidant properties. We have evaluated the neuromodulatory activity of M in brain tissue manifested in elevated levels of major neurotransmitters in healthy rodents and those with neurodegenerative changes accompanied by improvement in the animals` memory.Conclusion: Significant protective effects of myrtenal on neurodegenerative processes were established. Probably they are related to its complex mechanisms, including neuromodulatory and antioxidant properties

Nociceptin and Pilot Experiments to Detect Pharmacological Effects of its Short-Chain Analogues

Nociceptin, or orphanin FQ, is an endogenous ligand for the nociceptin receptor (NOP, ORL-1). It is a potent antianalgesic agent. The receptor is widely distributed in brain structures. Peptidomimetics are short-chain molecules designed to mimic peptides and with typical pharmacokinetic properties. The aim of the study is to investigate the basic pharmacological and toxicological effects of two newly-synthesized neuropeptides (P1 and P2) in mice. Their activity on the CNS and their inf luence on the hexobarbital- induced narcosis as well were studied. The analgesic activity of these two compounds was examined by using acetic acid test. Dose-dependent effect of the analgesic activity of compound P2 was independently studied by means of the same method. It was established that P2 possessed antinociceptive properties which makes it suitable for further research in this direction

ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY OF MONOTERPENOID MYRTENAL IN RODENTS

Inflammation and pain are common phenomena associated with a number of diseases. The search for new pharmacological agents is an important factor in delivering better therapy. Many plants and their active ingredients monoterpenes exhibit analgesic and anti-inflammatory activity but have not been fully studied. Purpose The bicyclic monoterpenoid Myrtenal (M) is a component of many plants essential oils. Researches on total plant extracts as well as on essential oils reveal a wide range of biological effects with various mechanisms. However, there is no data in the literature about Myrtenal effects in pain and inflammation. Aim of this study is to investigate the M effects in models of pain and inflammation in laboratory rodents. Materials and methods Anti-nociceptive activity of M (30 mg/kg, b. wt., i. p.) was tested in male ICR mice after single and repeated administration on two established experimental pain models - Acetic acid writhing test (antipyretic type analgesia) and Hot plate test (narcotic type analgesia). Anti-inflammatory activity of M (40 mg/kg, b. wt., i. p.) was evaluated on the 24th h from the last treatment after 5-d administration via carrageenan-induced inflammation model on rat paw and was compared with this of the non-steroid anti-inflammatory drug (NSAID) Ketoprofen (2.5 mg/kg, b. wt., i. p.) as a referent. Results In our experiments on Wistar rats and ICR mice M demonstrated significant anti-inflammatory and anti-nociceptive properties (toward both peripheral and thermal pain). In acute administration, significantly decreased the abdominal writhing number at 15th (p < 0.01) and 20th min (p < 0.05) by 47.25 % and by 50.55 % respectively. Myrtenal decreased (p < 0.001) the number of jumps versus control group after repeated treatment – by 40.4 % on 7th and by 43.1 % on the 14th d in comparison to the controls. Conclusions Possible mechanisms are complex, and they probably include sedative and antioxidant properties of Myrtenal

Zeolite and Neurodegenerative Diseases

Neurodegenerative diseases (NDs), characterized by progressive degeneration and death of neurons, are strongly related to aging, and the number of people with NDs will continue to rise. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs, and the current treatments offer no cure. A growing body of research shows that AD and especially PD are intricately related to intestinal health and the gut microbiome and that both diseases can spread retrogradely from the gut to the brain. Zeolites are a large family of minerals built by [SiO4]4− and [AlO4]5− tetrahedrons joined by shared oxygen atoms and forming a three-dimensional microporous structure holding water molecules and ions. The most widespread and used zeolite is clinoptilolite, and additionally, mechanically activated clinoptilolites offer further improved beneficial effects. The current review describes and discusses the numerous positive effects of clinoptilolite and its forms on gut health and the gut microbiome, as well as their detoxifying, antioxidative, immunostimulatory, and anti-inflammatory effects, relevant to the treatment of NDs and especially AD and PD. The direct effects of clinoptilolite and its activated forms on AD pathology in vitro and in vivo are also reviewed, as well as the use of zeolites as biosensors and delivery systems related to PD

Antioxidant mechanism in the preventive effect of myrtenal on Alzheimer`s disease progression on experimental mouse model

Introduction: Alzheimer’s disease (AD) is the most common form of dementia causing problems with mem-ory, thinking and behavior. So far there is no unified theory for AD pathogenesis and effective treatment. Scientific reports indicate many natural substances possessing neuroprotective properties. New studies demonstrated that natural monoterpen myrtenal combines antioxidant and anti-acetylcholinesterase activ-ity. Our unpublished data reveal significant improving effect of myrtenal on cognitive function of rodents. Aim: Goal of this study is to examine the effect of myrtenal on AD progression using animal model. Materials and Methods: Experimental model of dementia from AD type was produced on male Albino mice via scopolamine treatment (1 mg/kg i.p., 11 days) and was verified with cognitive test (Step through) and biochemical markers: lipid peroxidation and glutathione content in brain. Dement animals were treat-ed simultaneously with myrtenal (20 mg/kg i.p., 11 days). Its preventive effect was evaluated when compared with the effect of lipoic acid (30mg/kg i.p., 11 days) and galantamine (1 mg/kg i.p., 11 days) as referents. Data were analyzed using t-test of Student-Fisher.Results: Myrtenal produced a significant restoration of cognitive function (with 33%) in dement mice in comparison to scopolamine controls. In healthy rodents, myrtenal had antioxidant activity and decreased significantly brain lipid peroxidation, but in dement animals showed pro-oxidant activity. Administered to-gether myrtenal and lipoic acid demonstrated even better prevention on memory and also decreased estab-lished pro-oxidant activity of myrtenal in dement mice. Conclusion: Analyzed changed parameters (cognitive and biochemical) suggest antioxidant mechanism in myrtenal preventive effect on AD progression

Newly synthesized neuropeptides with central nervous activity in mice

Aim: Object of present study are two newly synthesized neuropeptides with short chains: analogues of Tyr-MIF – 1 with code P1 and of Nociceptine with code P2. Materials and Methods: On male albino mice we studied the changes in the cognitive functions of animals after 3, 7 and 14-days pretreatment with both compounds (5 mg/kg intraperitoneally- i.p.) via: step through test (for learning and memory), Rot-a-rod test (for muscular coordination) and Hole board test (for exploratory activity). Their potential analgesic effect was evaluated by Acetic acid test and their activity on the cen-tral nervous system (CNS) was evaluated via interaction with hexobarbital (HB- 100 mg/kg i.p). Statistics were performed with Student – Fisher test.Results: On the 3rd day after treatment daily both compounds had no effect on cognitive functions of animals, but on the 7th day the analogue of Tyr- MIF –1 (peptide P1) significantly improved the memory (by 60%) and decreased also the exploratory activity of treated animals. The analogue of Nociceptine-P2 demonstrated significant dose-dependent analgesic effect. On the 14th day both compounds improved neuro-muscular coordination of animals. In single doses two compounds shorten significantly duration of hexobarbital narcosis (Р1 by 40% and Р2 by 50%) via unknown mechanism, probably related to functional antagonism between the neuropeptides and hexobarbital on CNS level. Conclusion: Newly synthesized neuropeptides are promising biological active substances with effect on CNS. The analogue of Tyr-MIF–1 improves cognitive function of animals and the analogue of Nociceptine has significant dose-dependent analgesic effect

Gene Co-Expression Network Modular Analysis Reveals Altered Immune Mechanisms in HIV-HAND

Although the introduction of HAART has completely changed the natural course of HIV infection, the number of chronic forms of HIV-associated neurocognitive disorder (HAND) has risen. It is estimated that up to half of subjects undergoing HAART therapy exhibit mild cognitive impairments. In the current study, we apply the gene co-expression network modular analysis, a well-established system biology approach, to the gene expression profiles of cases from the National NeuroAIDS Tissue Consortium (NNTC). We observed a negative enrichment for genes associated with the control of immune responses and putatively regulated by the transcription factors IRF8 and SPI1 and by both type I and II interferons. Our study provides evidence of altered immune responses, which are likely associated with the occurrence of HAND in the absence of HIV encephalitis (HIVE)

Beneficial effect of melatonin on motor and memory disturbances in 6-OHDA-lesioned rats

Previous evidence has shown a link between neurodegenerative diseases, including Parkinson's disease (PD), and melatonin. The data in the literature about the impact of the hormone under different experimental PD conditions are quite controversial, and its effect on memory impairment in the disease is very poorly explored. The current research was aimed at investigating the role of melatonin pretreatment on memory and motor behavior in healthy rats and those with the partial 6-hydroxydopamine (6-OHDA) model of PD. All rodents were pretreated with melatonin (20 mg/kg, intraperitoneally) for 5 days. At 24 h and 7 days after the first treatment for healthy rats, and at the second and third week post-lesion for those with PD, the animals were tested behaviorally (apomorphine-induced rotations, rotarod, and passive avoidance tests). The neurochemical levels of dopamine (DA), acetylcholine (ACh), noradrenaline (NA), and serotonin (Sero) in the brain were also determined. The results showed that in healthy animals, melatonin pretreatment had amnestic and motor-suppressive effects and did not change the levels of measured brain neurotransmitters. In animals with PD, melatonin pretreatment exerted a neuroprotective effect, manifested as a significantly decreased number of apomorphine-induced rotations, reduced number of falls in the rotarod test, and improved memory performance. The brain DA and ACh concentrations in the same animals were restored to the control levels, and those of NA and Sero did not change. Our results demonstrate a beneficial effect of melatonin on memory and motor disturbance in 6-OHDA-lesioned rats

Development of N,N-Dimethylglycine-Amantadine for Adjunctive Dopaminergic Application: Synthesis, Structure and Biological Activity

N-methyl-D-aspartate (NMDA) receptor blockade can improve L-DOPA (l-3,4-dihydroxyphenylalanine)-induced dyskinesias in Parkinson’s disease (PD) patients. Amantadine is a well-tolerated and effective antiparkinsonian agent, recently found to possess NMDA antagonistic properties. Oxidative damage may contribute to dopaminergic (DAergic) neurodegeneration in the substantia nigra of patients with PD. N,N-dimethylglycine (DMG) (also known as vitamin B15 or pangamic acid) acts as an antioxidant, extending the lifespan of animal cells through protection from oxidation. In this study, we synthesized and tested in vivo the newly obtained compound N,N-dimethylglycine-amantadine (DMG-Am) for antiparkinsonian activity. MPTP (1-methyl-4–phenyl-1, 2, 3, 6-tetrahydropyridine) is a widely used neurotoxin to induce an experimental model which mimics Parkinson disease-like symptoms. The neuroprotective capacity of the new amantadine derivative DMG-Am was evaluated by its potential to ameliorate the neuromuscular coordination and behavioral changes worsened by the toxin. Our experimental results showed that DMG-Am applied for 12 consecutive days, 5 days simultaneously and 7 days after MPTP, restored motor and memory performance of the animals to the control level, indication of beneficial protective effect of this compound. In summary, our results reveal the potential of newly synthesized DMG-Am as promising antiparkinsonian agent

Effect of castalagin against HSV-1 infection in newborn mice

We tested in vivo anti-herpetic effect of castalagin, an ellagitannin compound, extracted from pedunculate oak (Quercus robur). Previous investigations found that castalagin possesses a strong inhibitory effect in vitro against HSV-1/2 equal to acyclovir (ACV). It is also effective against ACV-resistant mutants and shows a synergistic effect with ACV. We study castalagin’s activity towards HSV-1 infection in newborn mice. Acute toxicity determination in mice showed LD50 value of 295 mg/kg. Prolonged toxicity was also constructed. Castalagin manifested a marked activity against HSV-1 (LD90/0.02 ml) administered in 7-day course at 0.02 ml s.c. doses of 7.5 or 10 mg/kg (PI 57-58%). ACV course demonstrated a marked activity at 20 mg/kg. The selectivity ratio LD50/ED50 (295/7.5) could be accepted as ≥ 33.</p