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

Adamantane-containing drug delivery systems

Adamantane is a weakly functional hydrocarbon widely used to develop new drug molecules to improve their pharmacokinetic and pharmacodynamic parameters. The compound has an affinity for the lipid bilayer of liposomes, enabling its application in targeted drug delivery and surface recognition of target structures. This review presents the available data on developed liposomes, cyclodextrin complexes, and adamantane-based dendrimers. Adamantane has been used in two ways – as a building block to which various functional groups are covalently attached (adamantane-based dendrimers) or as a part of self-aggregating supramolecular systems, where it is incorporated based on its lipophilicity (liposomes) and strong interaction with the host molecule (cyclodextrins). Adamantane represents a suitable structural basis for the development of drug delivery systems. The study of adamantane derivatives is a current topic in designing safe and selective drug delivery systems and molecular carriers

The role of pharmacists in the identification, treatment and prevention of depressive disorders and stress-related pathology

Bulgaria is a country with high rates of suicide attempts and realized suicides, morbidity from unipolar depression, neurotic and eating disorders. Social instability, low income, and bullying at school and home create a high-stress medium. Chronic stress leads to intellectual and behavioral deficiencies which significantly worsen quality of life and productivity. The exact morbidity and prevalence are unknown because of persistent fear of stigmatization and misunderstanding. Attempts for self-medication with tobacco, alcohol and marijuana worsen the condition and create bigger problems with alcoholism and addictions.As the most accessible healthcare professionals, pharmacists can play an important role in the treatment and prevention of such disorders. A significant part of the patients prefer visiting the pharmacy for advice or recommendation before a visit to their GP, if such follows.Review of the tolerability, cost/effectiveness and risk/benefits ratios of the second generation of antidepressants, and especially SSRI`s class, shows that they have favorable profile and some meta-analysis show significant decline in suicide rates in countries with traditionally high baseline suicide rates.Giving pharmacy professionals prescription capabilities for the safest drugs can reduce the burden of the national healthcare and social systems, primarily by preventing serious healthcare issues by an early onset of proper treatment for mild cases and by more efficiently directing moderate-to-severe cases for psychiatric consultation

FACTORS LIMITING THE EFFECTIVENESS OF INTESTINAL PARASITOSES’ PHARMACOTHERAPY

The effective etiological antiparasitic treatment fulfils two major goals - to cure the infected patient and to terminate its role as an epidemiologically relevant source of infection. The purpose of this study is to evaluate the effectiveness of the pharmacotherapy against the most common intestinal helminthic and protozoal infections diagnosed in Varna region. Material and Methods: 879 patients with laboratory-confirmed intestinal parasitoses were treated etiologically with the established anthelminthic and antiprotozoal agents. Mandatory and active post-treatment laboratory monitoring served as the basis for the assessment of the therapy effectiveness. Results: Enterobiasis has the highest prevalence of the intestinal parasitic infections with estimated treatment success of 94,7% at the end of the mandatory period and nearly 100% at the end of our monitoring. The significantly greater rate of relapses was registered among the patients with the two most common protozoal invasions – Giardiasis (9,5%) and Blastocystosis (6,7 %). Our analysis established that the main factors limiting the effective antiparasitic pharmacotherapy are extraneous, i.e. independent of the pharmacological properties of the agent or parasite’s biology. The most prominent reasons for therapy failure are poor or missing compliance to the therapy regimen, inadequate form or dosage of the medication, unrecognized source of (re)invasion, etc. In conclusion, the collaboration between the general practitioners, clinical parasitologists and respectively the patients themselves is crucial for achieving an effective therapy and the resultant control of the intestinal parasitoses

Problems with prescribing, reading and dispensing of drugs, and education of students of pharmacy, medicine and dentistry

Medical services and care for patients today are increasingly liberalized and relying on awareness and active participation of the patient. But problems with the spelling and the correct allocation of prescription drugs remain. Many countries have introduced electronic prescriptions, which reduces the possibility of error to a minimum. In Bulgaria such a project is currently in progress.Will focus primarily on the problems at discharge and dispensing of medicines prescribed on regular (`white`) form - Ordinance № 4, Official Gazette No. 3, year LV, Annex 2 to Article 6, paragraph 1.The recipe is an official document with medical, legal and financial burden. We put emphasis on the responsibility that the pharmacist is often forced to take, performing incorrectly or illegibly written forms for humane reasons and not for financial reasons, as suspected.Training of medical professionals about the rules of prescription and dispensing of prescription drugs is subject to improvement. In this regard, the project `Updating the curricula of the Faculty of Pharmacy at the Medical University Varna in accordance with the needs of the pharmaceutical business and the requirements of the labor market` is absolutely necessary.Paying attention to this aspect of the work will improve the performance of pharmaceutical care in pharmacies and reduce the possibility of the occurrence of errors

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

Preventive and Therapeutic Effects of <i>Punica granatum</i> L. Polyphenols in Neurological Conditions

Pomegranate (Punica granatum L.) is a polyphenol-rich food and medicinal plant containing flavonols, anthocyanins, and tannins. Ellagitannins (ETs) are the most abundant polyphenols in pomegranate. A growing body of research shows that polyphenol-rich pomegranate extracts and their metabolites target multiple types of brain cell and support their redox balance, proliferation and survival, as well as cell signaling. Independent studies have demonstrated that the significant neuroprotective effects of ETs are mediated by their antioxidant and anti-inflammatory effects, their chelating properties, by their ability to activate various signaling pathways, as well as the ability to influence mitochondrial damage, thus regulating autophagy, apoptosis and neurotransmitter signaling. The multitude of in vitro and in vivo studies summarized in the present review suggest that pomegranate polyphenols act on both neuronal and glial cells directly, and also affect blood–brain barrier function, restoring redox balance in the blood and brain and increasing blood flow to the brain

Anti-COVID-19 Potential of Ellagic Acid and Polyphenols of <i>Punica granatum</i> L.

Pomegranate (Punica granatum L.) is a rich source of polyphenols, including ellagitannins and ellagic acid. The plant is used in traditional medicine, and its purified components can provide anti-inflammatory and antioxidant activity and support of host defenses during viral infection and recovery from disease. Current data show that pomegranate polyphenol extract and its ellagitannin components and metabolites exert their beneficial effects by controlling immune cell infiltration, regulating the cytokine secretion and reactive oxygen and nitrogen species production, and by modulating the activity of the NFκB pathway. In vitro, pomegranate extracts and ellagitannins interact with and inhibit the infectivity of a range of viruses, including SARS-CoV-2. In silico docking studies show that ellagitannins bind to several SARS-CoV-2 and human proteins, including a number of proteases. This warrants further exploration of polyphenol–viral and polyphenol–host interactions in in vitro and in vivo studies. Pomegranate extracts, ellagitannins and ellagic acid are promising agents to target the SARS-CoV-2 virus and to restrict the host inflammatory response to viral infections, as well as to supplement the depleted host antioxidant levels during the stage of recovery from COVID-19