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The investigation aimed to study the in vitro and in silico antioxidant properties of Melissa officinalis subsp. officinalis essential oil (MOEO). The chemical composition of MOEO was determined using GC–MS analysis. Among 36 compounds identified in MOEO, the main were beta-cubebene (27.66%), beta-caryophyllene (27.41%), alpha-cadinene (4.72%), caryophyllene oxide (4.09%), and alpha-cadinol (4.07%), respectively. In vitro antioxidant properties of MOEO have been studied in 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging, and inhibition of β-carotene bleaching assays. The half-maximal inhibitory concentration (IC50) for the radical scavenging abilities of ABTS and DPPH were 1.225 ± 0.011 μg/mL and 14.015 ± 0.027 μg/mL, respectively, demonstrating good antioxidant activity. Moreover, MOEO exhibited a strong inhibitory effect (94.031 ± 0.082%) in the β-carotene bleaching assay by neutralizing hydroperoxides, responsible for the oxidation of highly unsaturated β-carotene. Furthermore, molecular docking showed that the MOEO components could exert an in vitro antioxidant activity through xanthine oxidoreductase inhibition. The most active structures are minor MOEO components (approximately 6%), among which the highest affinity for the target protein belongs to carvacrol.

Melissa officinalis (MO), known as lemon balm, is a popular ingredient blended in herbal tea. In recent decades, the bioactivities of MO have been studied in sub-health and pathological status, highlighting MO possesses multiple pharmacological effects. We previously showed that hot water MO extract exhibited anticancer activity in colorectal cancer (CRC). However, the detailed mechanisms underlying MO-induced cell death remain elusive. To elucidate the anticancer regulation of MO extract in colon cancer, a data-driven analysis by proteomics approaches and bioinformatics analysis was applied. An isobaric tandem mass tags-based quantitative proteome analysis using liquid chromatography–coupled tandem mass spectrometry was performed to acquire proteome-wide expression data. The over-representation analysis and functional class scoring method were implemented to interpret the MO-induced biological regulations. In total, 3465 quantifiable proteoforms were identified from 24,348 peptides, with 67 upregulated and 54 downregulated proteins in the MO-treated group. Mechanistically, MO impeded mitochondrial respiratory electron transport by triggering a reactive oxygen species (ROS)-mediated oxidative stress response. MO hindered the mitochondrial membrane potential by reducing the protein expression in the electron transport chain, specifically the complex I and II, which could be restored by ROS scavenger. The findings comprehensively elucidate how MO hot water extract activates antitumor effects in colorectal cancer (CRC) cells.

Background: Emotional distress conditions such as depression, anxiety, stress, and poor sleep are widespread health problems that have a significant impact on people’s lives. Conventional drugs are commonly prescribed to treat emotional distress and poor sleep conditions; however, these medications have several limitations and have shown multiple side effects. Over recent years botanicals-based pharmacological agents have gained increasing research and clinical interest in the management of emotional distress and sleep disorder. Of note, Melissa officinalis L. (MO) leaf extract has demonstrated considerable neuropharmacological properties both in animal and human studies and has emerged as a promising natural “calming agent.” However, research in this area is limited, and more studies are needed to validate its efficacy in amelioration of emotional distress and poor sleep conditions. Objectives: We aimed to assess the pharmacological effects of subchronic supplementation of an innovative standardised phospholipid carrier-based MO aqueous extract on emotional distress and poor sleep conditions. Design: A 3-week prospective, randomised, placebo-controlled, parallel-group, double-blinded clinical trial was conducted in 100 healthy adults complaining of a moderate degree of depression, anxiety, or stress, with scores of ≥14, ≥10, and ≥19, respectively, in the self-report Depression, Anxiety, and Stress Scale (DASS-42) or poor sleep, as indicated by the score of >5 in the Pittsburgh Sleep Quality Index (PSQI) scale. In addition, the impact of emotional distress and/or poor sleep on participants’ mental wellbeing, emotional feelings, and quality of life was also assessed using the self-reported Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS), Positive and Negative Affect Schedule (PANAS) scale, and quality of life (WHO-QoL-BREF) scale, respectively. Results: Oral supplementation of 200 mg of phospholipid-based MO aqueous extract (Relissa™) tablets twice a day (i.e., 400 mg/day) for 3 weeks led to significant improvements in the depressive mood, anxiety, stress, positive and negative affect (emotional feelings), overall mental wellbeing, and quality-of-life scores (all p values <0.001). Supplementation of MO extract was well tolerated, and no treatment-emergent effects or serious adverse events were reported. Conclusion: According to the results of this study, the phospholipid carrier-based MO aqueous extract possesses considerable neuropharmacological properties, and its supplementation may provide a promising therapeutic option for the management of moderate emotional distress and/or poor sleep conditions. Clinical Trial Registration: clinicaltrials.gov , identifier NCT05602688.

Rosmarinic acid (RA), an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, is a potent radical scavenger, a chelator of prooxidant ions, and an inhibitor of lipid peroxidation. RA-containing extracts are widely used natural antioxidants in food products, and many herbal preparations and food supplements, containing RA, are marketed with claims of beneficial health effects. The current study investigated the effectiveness of subcritical water extraction (SWE) for the recovery of RA from lemon balm (Melissa officinalis), as a “green” alternative to conventional hydro-alcoholic extraction. Different durations (10 min and 20 min) and extraction temperatures (100 °C and 150 °C) were applied. Subcritical water applied at a temperature of 100 °C was equally efficient as 50% ethanol in extracting RA. However, the further elevation of temperature to 150 °C decreased RA content by up to 20% due to thermal degradation. The content of RA in dried extracts was between 2.36% and 5.55% and the higher temperature of SWE increased extract yield by up to 41%. The higher extraction yield resulted from the degradation of plant material by subcritical water as evidenced by the increased extraction and degradation of proteins, pectin, and cellulose. These results reveal that SWE is an efficient technology for the extraction of RA and other antioxidants from lemon balm at reduced extraction time and without the use of toxic organic solvents. Furthermore, by modification of SWE conditions, dry extracts with different purity and content of RA are obtained. These extracts could be used in the food industry as food antioxidants, or in the development of food supplements and functional foods.

Water deficit is one of the most detrimental environmental challenges that seriously impacts plant growth and agricultural productivity. In the current investigation, alterations induced by drought stress and exogenous application of sodium nitroprusside (SNP), as a NO donor, at the physiological, biochemical and molecular levels were studied in lemon balm ( Melisa officinalis L.) plant. Partial fragments of chlorophyllide a oxygenase (CAO) and Rubisco activase (RCA) genes were also isolated and sequenced in this study. Obtained results showed that limited water markedly induced oxidative damage and decreased the chlorophyll content and the level of relative water content (RWC) of the plant and resulted in significant inhibition of growth parameters. However, exogenous NO ameliorated the adverse impacts of limited water and accompanied with the better plant growth. Under this condition, supplementation of NO elevated both enzymatic and non-enzymatic antioxidant systems as indicated by increasing in activities of superoxide dismutase and catalase and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and ferric reducing antioxidant power (FRAP) capacities and greater accumulation of phenolic compounds. In this regard, stressed plants treated with NO exhibited lowered levels of lipid peroxidation, hydrogen peroxide and electrolyte leakage, increased transcript abundance of RCA and chlorophyll synthase (CHLG) genes and higher free proline and RWC levels. Results of the present study may be helpful in understanding mechanisms involved in NO-mediated drought adaptability in lemon balm.

The study reports efficacy of Melissa officinalis L. essential oil (MOEO) as a safe plant-based insecticide against Tribolium castaneum Herbst ( TC ) by induction of oxidative stress. MOEO nanoencapsulation in chitosan matrix was performed to enhance its bioefficacy. GC–MS analysis of MOEO depicted geranial (31.54%), neral (31.08%), and β-caryophyllene (12.42%) as the major components. MOEO showed excellent insecticidal potential in contact (100% mortality at 0.157 μL/cm 2 ) and fumigant bioassays (LC 50  = 0.071 μL/mL air) and 100% repellency at concentration ≤ 0.028 μL/cm 2 . Increased reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) at the LC 50 dose suggested significant oxidative stress on TC in MOEO treatment sets. The encapsulated MOEO exhibited enhanced activity as fumigant (LC 50  = 0.048 μL/mL air) and showed significant antifeedant activity in situ (EC 50  = 0.043 μL/mL). High LD 50 value (13,956.87 μL/kg body weight of mice) confirmed favorable toxicological profile for non-target mammals. The findings depict potential of nanoencapsulated MOEO as an eco-friendly green pesticide against infestation of stored food by TC .

In this study, we extracted essential oils from four species of plants with lemony scents ( Melissa officinalis L., Aloysia citriodora Palau (=  Lippia citriodora (Palau) Kunth), Thymus  ×  citriodorus , Perilla citriodora (Makino) Nakai). We then examined the components of extracts using gas chromatography (GC) and GC–mass spectrometry (GC–MS). A comparison of components indicated that the largest proportions of essential oils were caryophyllene (25%) in M. officinalis , geraniol (50%) in T. citriodorus , and citral (61 and 82%) in A. citriodora and P. citriodora . Moreover, we used a sensory evaluation method using dilute aqueous solutions of extract components, citral, linalool, d- limonene, and geraniol, to select the mixture with a flavor that mostly resembled lemon. The participants in the study felt that an aqueous citral solution flavored more like lemon than aqueous d- limonene. Furthermore, an open field study of sedative effects of citral and d -limonene, when inhaled, on mice demonstrated that citral exhibited a sedative effect at a lower concentration than that of d -limonene.

Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may reduce diabetes-associated neurological comorbidities. Natural remedies containing phenolic compounds have shown efficacy in mitigating microglia-mediated neuroinflammation. The aim of this study was to investigate the potential of a Melissa officinalis L. (MO) phytocomplex, obtained from plant cell cultures and enriched in its main polyphenolic constituent, rosmarinic acid (RA), in attenuating hyperglycemia-induced neuroinflammation in microglia. A time-course morphological analysis of BV2 microglial cells exposed to high glucose (HG) levels showed a shift towards a proinflammatory phenotype, peaking after 48 h, which was reversed by pretreatment with MO. Biochemical assays revealed increased expression of the microglial marker CD11b (187%), activation of the NF-κB pathway (179%), expression of iNOS (225%), enhanced phosphorylation of ERK1/2 (180%), and increased expression of the proinflammatory cytokine IL-6 (173%). Pretreatment with MO prevented the aberrant expression of these proinflammatory mediators and restored SIRT1 levels. Exposure of neuronal SH-SY5Y cells to the conditioned medium from HG-exposed microglia significantly reduced cell viability. MO counteracted this effect, exhibiting neuroprotective activity. RA showed efficacy comparable to that of MO. In conclusion, MO and RA attenuated microglia-mediated oxidative imbalance and neuroinflammation under HG exposure by inhibiting the morphological shift toward a proinflammatory phenotype induced by HG and abrogating the subsequent activation of the downstream ERK1/2–NF-κB–iNOS pathway.

This study describes the minerals elements, chemical composition, antioxidant and antimicrobial activities of Algerian Melissa officinalis plant. The essential oil (EO) was extracted by hydrodistillation (HD) using a Clevenger-type apparatus of dry leaves of M. officinalis and was analyzed by two techniques, gas chromatography coupled with flame ionization (GC-FID) and gas chromatography coupled with mass spectrometry (GC-MS). Eighteen minerals comprising both macro- and microelements (As, Br, K, La, Na, Sb, Sm, Ba, Ca, Ce, Co, Cr, Cs, Fe, Rb, Sc, Th, and Zn) were determined using neutron activation analysis technique for the first time from Algerian Melissa officinalis plant. Seventy-eight compounds were identified in the essential oil, representing 94.090% of the total oil and the yields were 0.470%. The major component was geranial (45.060%). Other predominant components were neral (31.720%) and citronellal (6.420%). The essential oil presented high antimicrobial activity against microorganisms, mainly five human pathogenic bacteria, one yeast, Candida albicans, and two phytopathogenic fungi. The results can be used as a source of information for the pharmaceutical industry and medical research.

Objective Psoriasis is an immune-mediated inflammatory skin disease. It can involve any body skin area, particularly the scalp, lower back, elbows, and knees. There are several topical and systemic therapies for the treatment. Nowadays, herbal medicines are popular treatments for dermatologic conditions. This two-arm parallel, randomized placebo-controlled clinical trial was conducted to examine the hypothesis of the efficacy of Melissa officinalis syrup on patients with mild-to-moderate Plaque psoriasis. Result Among 100 patients, 95 participants completed the trial and five of them withdrew. The mean pruritus intensity and PASI scores decreased significantly in the intervention group compared to the placebo group (P < 0.001). The DLQI score in the intervention group increased post-treatment compared to pre-treatment (P = 0.029); however, there was no significant difference between the intervention and control group at the end of the study (0.065). Trial registration : The trial was registered in the Iranian registry of clinical trials on November 9th, 2019 ( https://www.irct.ir/trial/43434 ; registration number: IRCT20191104045326N1).