Melissa officinalis L. - A review of its traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. is a medicinal plant that has long been used in different ethno-medical systems especially in the European Traditional Medicine and the Iranian Traditional Medicine for the treatment of several diseases. It is also widely used as a vegetable and to add flavor to dishes AIM OF THE REVIEW: This review aimed to provide a summary on the botanical characterization, traditional uses, phytochemistry, pharmacological activities, pharmacokinetics and toxicity of M. officinalis, and discusses research gaps and future opportunities for investigations on this plant. MATERIALS AND METHODS: We extensively reviewed major unpublished old texts, and published and electronic literature on traditional medicines of different regions of the world to find traditional uses of M. officinalis. Electronic databases including Web of Science, PubMed, ScienceDirect, Google Scholar and Scopus were searched to find articles (published between 1956 and 2015) on pharmacology and phytochemistry of M. officinalis. RESULTS: Traditional uses of M. officinalis have been recorded mostly in European countries, Mediterranean region and Middle East countries. Phytochemical investigations revealed that this plant contains volatile compounds, triterpenoids, phenolic acids and flavonoids. Crude extracts and pure compounds isolated from M. officinalis exhibited numerous pharmacological effects, from which only anxiolytic, antiviral and antispasmodic activities of this plant as well as its effects on mood, cognition and memory have been shown in clinical trials. AChE inhibitory activity, stimulation of the acetylcholine and GABAA receptors, as well as inhibition of matrix metallo proteinase-2 are the main mechanisms proposed for the widely discussed neurological effects of this plant. CONCLUSIONS: Modern pharmacological studies have now validated many traditional uses of M. officinalis. The data reviewed here revealed that M. officinalis is a potential source for the treatment of a wide range of diseases especially anxiety and some other CNS disorders, though confirmatory trials are warranted to substantiate these effects in the clinical setting. Data regarding many aspects of this plant such as mechanisms of actions, pharmacokinetics, adverse effects of the extracts, potential interactions with standard-of-care medications and active compounds is still limited which call for additional studies particularly in humans.

Pharmacokinetics, Safety and Tolerability of Melissa officinalis Extract which Contained Rosmarinic Acid in Healthy Individuals: A Randomized Controlled Trial.

The aim of this study was to evaluate the safety, tolerability and pharmacokinetics of single dose of Melissa officinalis extract which contained rosmarinic acid, including food-effects in healthy individuals. A total of eleven healthy individuals were randomly assigned to treatment arms in the two studies [Study 1 (fasted state) and Study 2 (fed state)]. Rosmarinic acid in serum was measured by a coulometric detection method using High-Performance Liquid Chromatography electrochemical detector. The serum concentration of total rosmarinic acid peaked at 1 hour after administration of Melissa officinalis extract containing 500mg rosmarinic acid in fasted state, with a maximum serum concentration 162.20 nmol/ L. The area under the curve for intact rosmarinic acid was calculated from the serum concentration-time profile to be 832.13 nmol • hour/ L. Food intake increases area under the curve and delayed time at which the maximum serum concentration. Rosmarinic acid supplementation did not affect liver, kidney, or blood cell function parameters. No adverse event was reported by any of the participants due to the study treatment. Single dose of Melissa officinalis extract containing 500 mg rosmarinic acid appears to be safe and tolerable in healthy individuals. Food intake increased the exposure of rosmarinic acid and delayed absorption of rosmarinic acid in healthy individuals.

Does melissa officinalis cause withdrawal or dependence?

INTRODUCTION: Melissa officinalis is a medical and aromatic plant that is used for its hypnotic, sedative, and spasmolytic effects. This report presents a case study of30-year-old patient who was admitted to an emergency department with restlessness, tremor, distractibility, and sweating following a discontinuation of Melissa officinalis consumption. CASE REPORT: In this case, withdrawal symptoms may be related to the dependence effect caused by long-term use of Melissa officinalis. Although Melissa officinalis, a plant, is preferred by many patients as an alternative to pharmaceutical drugs, patients should be made aware that it may have a risk of dependency and can lead to withdrawal symptoms.

A double-blind placebo-controlled randomized trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimer's disease.

BACKGROUND/AIMS: Behavioural and psychological symptoms (BPSD) are frequent in people with Alzheimer's disease and cause considerable stress to patients and their carers. Antipsychotics have been widely used as a first-line treatment, resulting in an estimated 1,800 excess strokes and 1,600 excess deaths in the UK alone. Safe and effective alternatives are urgently needed. Based upon preliminary evidence from clinical trials, aromatherapy with melissa oil may be such an alternative, but initial studies have been modest in size, and adequate blinding has been problematic. Our objective was to assess the efficacy of melissa aromatherapy in the treatment of agitation in people with Alzheimer's disease in an adequately powered and robustly blinded randomized controlled trial comparing it with donepezil, an anticholinesterase drug used with some benefit to treat BPSD. METHODS AND FINDINGS: The study was a double-blind parallel-group placebo-controlled randomized trial across 3 specialist old age psychiatry centres in England. Participants had probable or possible Alzheimer's disease, were resident in a care home, had clinically significant agitation (defined as a score of 39 or above on the Cohen Mansfield Agitation Inventory) and were free of antipsychotics and/or anticholinesterase for at least 2 weeks. Participants were allocated to 1 of 3 groups: placebo medication and active aromatherapy; active medication and placebo aromatherapy or placebo of both. MAIN OUTCOME: The primary outcome measure was reduction in agitation as assessed by the Pittsburgh Agitation Scale (PAS) at 4 weeks. This is an observational scale, and raters were required to wear nose clips to ensure that full blinding was maintained. The PAS, Neuropsychiatric Inventory (NPI; another measure of BPSD) and other outcome measures were completed at baseline, 4-week and 12-week follow-ups. 114 participants were randomized, of whom 94 completed the week 4 assessment and 81 completed the week 12 assessment. Aromatherapy and donepezil were well tolerated. There were no significant differences between aromatherapy, donepezil and placebo at week 4 and week 12, but importantly there were substantial improvements in all 3 groups with an 18% improvement in the PAS and a 37% improvement in the NPI over 12 weeks. CONCLUSION: When assessed using a rigorous design which ensures blinding of treatment arms, there is no evidence that melissa aromatherapy is superior to placebo or donepezil, in the treatment of agitation in people with Alzheimer's disease. However, the sizeable improvement in the placebo group emphasizes the potential non-specific benefits of touch and interaction in the treatment of agitation in people with Alzheimer's disease.