Bibliometric Analysis and Visualization of Clinical Trials on the Therapeutic Potential of Essential Oils (1967-2024).

Essential oils, aromatic compounds extracted from various parts of plants, have garnered significant attention in recent years due to their diverse therapeutic properties and potential applications in healthcare. This analysis delves into the publication trends, productivity patterns, most relevant contributors, coauthorship networks, most frequently used keywords, and their co-occurrence, topic trends, thematic evolution, and collaboration between various countries in clinical trials exploring the therapeutic potential of essential oils. Six hundred sixty-one clinical trials were selected from the PubMed database for analysis, authored by 2959 authors, and published across 359 sources. The analysis identified Horrobin DF as the most contributing author based on the number of published clinical trials, followed by Kasper S, McGuire JA, and Schlafke S. Lotka's law underscores the distribution of authors' productivity, revealing a small number of highly productive authors. Coauthorship analysis identifies significant collaborations among authors and institutions, with prominent contributors like Siegfried Kasper and institutions like Shiraz University of Medical Sciences. Furthermore, the analysis highlights leading journals like Complementary Therapies in Clinical Practice and the Journal of Alternative and Complementary Medicine. Using keyword clustering, connections between various subjects and their chronological presence are uncovered, offering insights into the changing research landscape. The thematic examination exposes changes in research emphasis over time, progressing from fundamental studies on essential oil components to broader utilization and focused inquiries into oils and therapeutic domains. Analysis of the countries of corresponding authors revealed that Iran has the highest number of multiple-country publications. Moreover, international collaboration trends have been unveiled. Together, these analyses furnish holistic understandings of keyword relationships, thematic shifts, and global partnerships in essential oil research, presenting valuable perspectives on trends and focal points within this domain.

Unveiling the pharmacological potential of Coelogyne suaveolens: An investigation of its diverse pharmacological activities by in vivo and computational studies.

The medicinal potential of Coelogyne suaveolens, a traditional medicinal plant, was investigated through in vivo and molecular docking studies. The ethyl acetate fraction of the plant's acetonic extract was subjected to various bioactivity tests to assess its analgesic, anxiolytic, and sedative effects on Swiss albino mice. Furthermore, we used GCMS to identify the bioactive chemicals in the extract's ethyl acetate fraction. The root and bulb extracts demonstrated significant analgesic activity in acetic acid-induced writhing, hot plate, and tail immersion tests in a dose-dependent manner when compared to the control. Again, the extract exhibited moderate anxiolytic activity in the elevated plus maze test at a dosage of 400 mg/kg body weight, while the root extract showed significant anxiolytic activity in the hole board test at the same dosage. Significant sedative activity was observed in the hole cross, open field, and rotarod tests at a dosage of 400 mg/kg. According to molecular docking studies, the extract has the potential to serve as an analgesic medication by reducing the enzymatic activity of cyclooxygenases 1 and 2. Overall, the findings suggest that C. suaveolens has substantial therapeutic potential for the development of novel treatments for pain, anxiety, and sleep disorders.

Inhaled Litsea glaucescens K. (Lauraceae) leaves' essential oil has anxiolytic and antidepressant-like activity in mice by BDNF pathway activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Litsea glaucescens K. (Lauraceae) is a small tree from the Mexican and Central American temperate forests, named as "Laurel". Its aromatic leaves are ordinarily consumed as condiments, but also are important in Mexican Traditional Medicine, and among the most important non wood forest products in this area. The leaves are currently used in a decoction for the relief of sadness by the Mazahua ethnic group. Interestingly, "Laurel" has a long history. It was named as "Ehecapahtli" (wind medicine) in pre-Columbian times and applied to heal maladies correlated to the Central Nervous System, among them depression, according to botanical texts written in the American Continent almost five centuries ago. AIM OF THE STUDY: Depression is the first cause of incapacity in the world, and society demands alternative treatments, including aromatherapy. We have previously demonstrated the antidepressant-like activity of L. glaucescens leaves' essential oil (LEO), as well as their monoterpenes linalool, and beta-pinene by intraperitoneal route in a mice behavioral model. Here we now examined if LEO and linalool exhibit this property and anxiolytic activity when administered to mice by inhalation. We also investigated if these effects occur by BDNF pathway activation in the brain. MATERIALS AND METHODS: The LEO was prepared by distillation with water steam and analyzed by gas chromatography-mass spectrometry (GC-MS). The monoterpenes linalool, eucalyptol and ß-pinene were identified and quantified. Antidepressant type properties were determined with the Forced Swim Test (FST) on mice previously exposed to LEO or linalool in an inhalation chamber. The spontaneous locomotor activity and the sedative effect were assessed with the Open Field Test (OFT), and the Exploratory Cylinder (EC), respectively. The anxiolytic properties were investigated with the Elevated Plus Maze Apparatus (EPM) and the Hole Board Test (HBT). All experiments were video documented. The mice were subjected to euthanasia, and the brain hippocampus and prefrontal cortex were dissected. RESULTS: The L. glaucescens essential oil (LEO) contains 31 compounds according to GC/MS, including eucalyptol, linalool and beta-pinene. The LEO has anxiolytic effect by inhalation in mice, as well as linalool, and ß-pinene, as indicated by OFT and EC tests. The LEO and imipramine have antidepressant like activity in mice as revealed by the FST; however, linalool and ketamine treatments didn't modify the time of immobility. The BDNF was increased in FST in mice treated with LEO in both areas of the brain as revealed by Western blot; but did not decrease the level of corticosterone in plasma. The OFT indicated that LEO and imipramine didn't reduce the spontaneous motor activity, while linalool and ketamine caused a significant decrease. CONCLUSION: Here we report by the first time that L. glaucescens leaves essential oil has anxiolytic effect by inhalation in mice, as well as linalool, and ß-pinene. This oil also maintains its antidepressant-like activity by this administration way, similarly to the previously determined intraperitoneally. Since inhalation is a common administration route for humans, our results suggest L. glaucescens essential oil deserve future investigation due to its potential application in aromatherapy.

Assessment of the anxiolytic, antidepressant, and antioxidant potential of Parquetina nigrescens (Afzel.) Bullock in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The recent growing concerns about the multisystemic nature of mental health conditions in the global population are facilitating a new paradigm involving alternative natural, nutritional, and complementary therapies. Herbal remedies despite accounts in literature of their ethnobotanical as alternative remedies for diverse ailments, remain underexplored for psychiatric disorders like anxiety, depression, and insomnia. AIM OF THE STUDY: Hence, the anxiolytic, antidepressant, and antioxidant properties of a hydro-ethanolic leaf extract of Parquetina nigrescens (PN) in male Wistar rats were investigated. MATERIALS AND METHODS: The sedative effect was evaluated using the Diazepam sleeping time test while anxiety was induced with a single intraperitoneal injection of 20 mg/kg pentylenetetrazol (PTZ). This was after pre-treatment with 100, 150, and 250 mg/kg of PN or the standard drugs (1 mg/kg diazepam and 30 mg/kg imipramine) for 14 consecutive days. Behavioral tests (Open Field test, Elevated Plus-Maze test, and Forced Swim test) were performed on days 1 and 14, to evaluate the antidepressant and anxiolytic activities of PN. Oxidative stress and neurochemical markers were determined in the brain homogenates of the animals. RESULTS: The duration of sleep was significantly (p < 0.001) increased in the PN-administered group compared to the control. The behavioral models showed that PN exhibited antidepressant and anxiolytic properties in PTZ-induced animals. Significant reductions were observed in GSH level and SOD activity while MDA, nitrite, and GPx levels were significantly increased in PTZ-induced rats. However, treatment with PN significantly improved brain antioxidant status by ameliorating the PTZ-induced oxidative stress. Dopamine, cortisol, and acetylcholine esterase activity levels were significantly (p < 0.05) elevated while serotonin and brain-derived neurotrophic factors were reduced in PTZ-induced rats compared with the control. CONCLUSION: The PN demonstrated neurotransmitter modulatory ability by ameliorating the PTZ-induced neurochemical dysfunction. Findings from this study showed that PN exhibited sedative, antidepressant, and anxiolytic activities in rats.

Therapy and Prevention of Noise Fears in Dogs-A Review of the Current Evidence for Practitioners.

Noise fears represent the most common behavioural problem in dogs. This manuscript provides an overview of diverse approaches for alleviating fear of noises in dogs and the supporting evidence. In the treatment of noise fears, both short-term solutions to prevent trauma or the deterioration of fear during unavoidable noise events and longer-term training need to be considered. Environmental management, the provision of incentives (food/play) during noise exposure, and, when indicated, anxiolytic medication, can safeguard dogs' welfare during noise events. Most "alternative" products (such as nutraceuticals, herbal remedies, pheromones, homeopathy, Bach flowers, and essential oils) are unlikely to be sufficient as monotherapy for noise fears, whereas there is good evidence for the efficacy of several anxiolytic medications. In the longer term, counterconditioning to real-life noises, relaxation training, and desensitisation/counterconditioning using noise recordings have been shown to improve fear of noises in dogs. Preventative training appears to be highly effective in preventing the development of noise fears in puppies and adult dogs.

(Bio)active Compounds in Daisy Flower (Bellis perennis).

The common daisy (Bellis perennis) belongs to the family Asteraceae and, in recent years, some new research has been published on the bioactive compounds and biological activities of its extracts. In 2014, the knowledge was partially summarized, but several new studies have been published in the last nine years. In addition, the substances were tabularly consolidated to give a comprehensive overview of over 310 individual components, compound classes, and bioactivities, as well as their accurate plant organ origin. The latest results have shown that the plant has antioxidative, antimicrobial, anticancerogenic, wound healing, antidepressive, anxiolytic, nephroprotective, and insulin mimetic effects, as well as an effect on lipid metabolism. Some studies in the field of homeopathy were also listed. Ideally, a biological effect and one or several compound(s) can be correlated. However, the compounds of the extracts used have often been qualified and quantified, but it remains unclear which of these substances have an activity. The works often stick at the level of the crude extract or a fraction, but not at a single purified and tested compound and, consequently, they are hampered by a missing comprehensive bioactivity workflow. This review provides a critical overview and gaps and offers a basis for further research in this area.

The Effect of Music on Operative Anxiety markers in patients undergoing Cataract Surgery: Adual centre cross-sectional comparative study.

OBJECTIVE: To determine the effect of intraoperative music on various markers of anxiety among adult patients undergoing small incision cataract surgery. METHODS: This was a hospital-based, age-sex matched, comparative cross-sectional study of consenting 144 adult participants aged 46 years and above with operable, age-related cataracts undergoing small incision cataract surgery under local anaesthesia in two ophthalmic centres. All participants were allotted into two equal groups consisting of 72 participants in the experimental group (exposed to music of their choice) and 72 participants in the control group (no music exposure). Blood pressure, pulse rate and salivary cortisol assay levels were measured. Data obtained were analyzed using statistical package for social sciences (IBM SPSS version 23.0). RESULTS: One hundred and forty-four participants with total male-to-female ratio of 1:2.1 were studied. Gender ratio was 1:2.3 and 1:2.0 and the median age (Q1-Q3) of 65.00 (55.5-71.5) years and 65.50 (56.5-72.0) years for music and non-music groups respectively. Participants in the music group showed a statistically significant reduction in systolic blood pressure, diastolic blood pressure and pulse rate (p < 0.05) except at baseline. The mean value salivary cortisol level showed a statistically significant decrease in both groups from baseline for music (23.91ng/ml) and nonmusic (19.12ng/ml) group (p<0.001) respectively. Similarly, participants in the music group showed a statistically significant reduction of Spielberger State anxiety score after music intervention compared to control (p<0.001). CONCLUSIONS: This study demonstrated the effectiveness of music in decreasing anxiety indicators during cataract surgery with markers like salivary cortisol assay, pulse rate, systolic and diastolic blood pressure.

OBJECTIF: Déterminer l'effet de la musique intra-opératoire sur divers marqueurs d'anxiété chez les patients adultes subissant une chirurgie de la cataracte par petite incision. MÉTHODES: Il s'agissait d'une étude transversale comparative, basée à l'hôpital, appariée selon l'âge et le sexe, portant sur 144 participants adultes consentants âgés de 46 ans et plus, présentant des cataractes liées à l'âge opérables et subissant une chirurgie de la cataracte par petite incision sous anesthésie locale dans deux centres ophtalmologiques. Tous les participants ont été répartis en deux groupes égaux, soit 72 participants dans le groupe expérimental (exposé à de la musique de leur choix) et 72 participants dans le groupe témoin (pas d'exposition à la musique). La pression artérielle, la fréquence cardiaque et les taux de cortisol salivaire ont été mesurés. Les données obtenues ont été analysées à l'aid du logiciel statistique pour les sciences sociales (IBM SPSS version 23.0). RÉSULTATS: Cent quarante-quatre participants avec un rapport total d'hommes à femmes de 1:2,1 ont été étudiés. Le ratio hommes-femmes était de 1:2,3 et 1:2,0, avec un âge médian (Q1-Q3) de 65,00 (55,5-71,5) ans et 65,50 (56,5-72,0) ans pour les groupes musique et non-musique, respectivement. Les participants du groupe musique ont montré une réduction statistiquement significative de la pression artérielle systolique, de la pression artérielle diastolique et de la fréquence cardiaque (p < 0,05) sauf au départ. La valeur moyenne du taux de cortisol salivaire a montré une diminution statistiquement significative dans les deux groupes par rapport au départ pour le groupe musique (23,91 ng/ml) et le groupe non-musique (19,12 ng/ml) (p <0,001) respectivement. De même, les participants du groupe musique ont montré une réduction statistiquement significative du score d'anxiété à l'état de Spielberger après l'intervention musicale par rapport au groupe témoin (p <0,001). CONCLUSIONS: Cette étude a démontré l'efficacité de la musique dans la diminution des indicateurs d'anxiété pendant la chirurgie de la cataracte, avec des marqueurs tels que le dosage du cortisol salivaire, la fréquence cardiaque, la pression artérielle systolique et diastolique. Mots-clés: Musique binaurale, peur, anxiété, stress, chirurgie de la cataracte par petite incision, anxiolytique non pharmacologique.

Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine.

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography-mass spectrometry (GC-MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1-50 mg/kg p.o.) and DHS (0.1-10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1-50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.

Pomegranate (Punica granatum L.) and its phytochemicals as anxiolytic; an underreported effect with therapeutic potential: A systematic review.

Anxiety is a mental disorder characterized by excessive concern about possible future threats that, if prolonged, becomes a pathology that must be controlled through psychotherapy and medication. Currently, the pharmacological treatment for anxiety involves the use of antidepressants and benzodiazepines; however, these treatments often come with adverse effects. Thus, there is a need to seek natural compounds that can help alleviate anxiety and reduce these side effects. On the other hand, pomegranate (PG) fruit is known to have important health benefits, which have been compiled in several reviews. However, its anxiolytic effect has not been thoroughly studied, and clinical research on this topic is lacking. The aim of this work was to conduct a systematic review of studies exploring the anxiolytic-like effect of PG and its phytochemicals. Databases such as Pubmed, ScienceDirect, Springer link, Google scholar, Worldwide science, and Web of science were searched for articles using predetermined terms. Inclusion criteria were established, and original articles that met these criteria were selected. The data collected included information on PG part and variety, species, sample size, anxiety model, dose, route and time of administration, reference drug, main results, and the mechanisms of action. Fifty-nine studies were found that reported the anxiolytic-like effect of PG and its phytochemicals such as anthocyanins, flavonoids, tannins, organic acids, and xanthonoids. The literature suggests that the mechanisms of action behind this effect involved the inhibition of the GABAergic receptor, NMDA, CaMKII/CREB pathway; the reduction of oxidative stress, inhibiting TLR4 and nNOS; modulation of cytokines and the expression of NFkB, GAD67, and iNOS, as well as the activation of Nrf2 and AMPK. PG and some of its phytochemicals could be considered as a novel alternative for the treatment of pathological anxiety. This review is the first to document the anxiolytic-like effect of PG.

Lateral hypothalamic orexin neurons mediate electroacupuncture-induced anxiolytic effects in a rat model of post-traumatic stress disorder.

The lateral hypothalamus' orexinergic system has been associated with anxiety-related behaviors, and electroacupuncture (EA) modifies orexin neurons to control the anti-anxiety process. However, in a rat model of post-traumatic stress disorder (PTSD), the important role of LH orexin neurons (OXNs) in the anxiolytic effects induced by EA has not been explored. In this study, rats underwent modified single prolonged stress (MSPS) for seven days before developing EA. The rats were then subjected to elevated plus maze (EPM) and open field (OFT) tests, and western blot and c-Fos/orexin double labeling investigations were carried out to determine the functional activation of LH orexinergic neurons. Compared to MSPS model rats, it has been demonstrated that EA stimulation enhanced the amount of time spent in the central zone (TSCZ) in OFT and the amount of time spent in the open arm (TSOA) in EPM in MSPS model rats (P < 0.01). After behavioral testing, MSPS model rats had decreased activated c-Fos positive OXNs. Still, EA in SPS rats increased that number and elevated orexin type 1 receptors (OXR1) protein expression in the LH. Furthermore, after administering SB334867 (an OXR1 antagonist) to MSPS model rats, the effects of EA therapy on anxiety-like behaviors (ALBs) were significantly diminished. Additionally, when low-dose orexin-A (LORXA) was administered intracerebroventricularly together with EA stimulation in MSPS rats, the anxiolytic effects of the stimulation were substantially enhanced (P < 0.05). The results of this study reveal the mechanisms by which acupuncture may reduce PTSD and advance our understanding of the function of LH orexin signaling in EA's anxiolytic effects.

Lasia spinosa (L.) thw. attenuates chemically induced behavioral disorders in experimental and computational models.

Lasia spinosa (L.) Thw. (L. spinosa) is widely used as a folk remedy for different physical ailments, and its neurological effects have yet to be assessed. Phytochemicals status of L. spinosa was evaluated by GC-MS analysis. Membrane stabilization test, elevated plus maze (EPM) tests and hole board tests (HBT), tail suspension tests (TST) and thiopental sodium-induced sleeping tests (TISTT) were used to assess anti-inflammatory, anxiolytic and anti-depressant activity. Fourteen compounds have been recorded from GC-MS analysis. The LSCTF showed 68.66 ± 2.46% hemolysis protections (p < 0.05) at 500 µg/mL, whereas LSCHF and LSNHF demonstrated efficiency rates of 68.6 ± 1.46% and 52.46 ± 5.28%, respectively. During EPM tests, LSNHF and LSCTF significantly (p < 0.001) increased the time spent in the open arm (59.88 ± 0.65 s and 50.77 ± 0.67 s, respectively) at the dosages of 400 mg/kg. In HBT, samples exhibited dose-dependent anxiolytic activity. LSNHF and LSCTF showed a significant (p < 0.001) hole poking tendency and a high number of head dips (78.66 ± 1.05 and 65.17 ± 0.96, respectively) at the higher dose. In TST, at 400 mg/kg dose demonstrated significantly (p < 0.001) smaller amounts of time immobile, at 81.33 ± 1.67 s and 83.50 ± 1.90 s, respectively, compared to the control group. A consistent finding was also observed in TISTT. The computer-assisted studies on the identified compounds strongly support the aforementioned biological activities, indicating that L. spinosa has potential as a source of medication for treating neuropsychiatric and inflammatory diseases.

Quantitative-HPLC-DAD polyphenols analysis, anxiolytic and cognition enhancing potentials of Sorbaria tomentosa Lindl. Rehder.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants of the family Rosaceae have a long history of traditional uses in the management of neurological disorders. Sorbaria tomentosa Lindl. Rehder is composed of antioxidant and neuroprotective polyphenolics. AIMS OF THE STUDY: The current study was designed to explore phenolics profile via high performance liquid chromatography-photodiode array detector (HPLC-DAD) and validated the neuroprotective and anxiolytic potentials of S. tomentosa by applying in vitro and in vivo approaches. MATERIALS AND METHODS: The plant crude methanolic extract (St.Crm) and fractions were subjected to HPLC-DAD analysis for qualitative and quantitative assessment of phytochemicals. Samples were screened for in vitro free radicals scavenging assays by using 2,2-diphenylpicrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) along with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibition assays. For cognitive and anxiolytic studies, mice were subjected to open field, elevated plus maze (EPM), light-dark model, Y-maze, shallow water maze (SWM), and novel object recognition (NOR) tests. RESULTS: HPLC-DAD analysis revealed the presence of high concentrations of phenolic compounds. For instance, in St.Cr, 21 phenolics were quantified, among which apigenin-7-glucoside (291.6 mg/g), quercetin (122.1 mg/g), quercetin-3-feruloylsophoroside-7-glucoside (52.6 mg/g), quercetin-7-glucoside (51.8 mg/g), ellagic acid (42.7 mg/g), luteolin (45.0 mg/g), kaempferol (40.5 mg/g), 5-feruloylquinic acid (43.7 mg/g) were present in higher concentrations. Likewise, in ethyl acetate fraction (St.Et.Ac), 21 phenolics were identified as 3,5-di-caffeoylquinic acid (177.4 mg/g) and 5-hydroxybenzoylquinic acid (46.9 mg/g) were most abundant phytochemicals. Highly valuable phenolics were also identified in other fractions including butanol (St.Bt), chloroform (St.Chf), and n-hexane (St.Hex). The various fractions exhibited concentration dependent inhibition of free radicals in DPPH and ABTS assays. Potent AChE inhibitory potentials were revealed by the test samples with St.Chf, St.Bt and St.EtAc being the most active having an IC50 of 298.1, 580.1, and 606.47 µg mL-1, respectively. Similarly, St.Chf, St.Bt, St.EtAc and St.Cr exhibited potent BChE inhibitory activity and was observed as 59.14, 54.73, 51.35 and 49.44%, respectively. A significant improvement in the exploratory behavior was observed in open field test and stress/anxiety was relieved effectively at 50-100 mg/kg. Likewise, EPM, light-dark and NOR tests revealed an anxiolytic and memory enhancing behaviors. These effects were further corroborated from the Y-maze and SWM transgenic studies that showed considerable improvement in cognition retention. CONCLUSIONS: These findings concluded that S. tomentosa possessed potential anxiolytic and nootropic efficacies and may have therapeutic potential in neurodegenerative disorders.

Anxiolytic, Analgesic and Anti-Inflammatory Effects of Peptides Hmg 1b-2 and Hmg 1b-4 from the Sea Anemone Heteractis magnifica.

Acid-sensing ion channels (ASICs) have been known as sensors of a local pH change within both physiological and pathological conditions. ASIC-targeting peptide toxins could be potent molecular tools for ASIC-manipulating in vitro, and for pathology treatment in animal test studies. Two sea anemone toxins, native Hmg 1b-2 and recombinant Hmg 1b-4, both related to APETx-like peptides, inhibited the transient current component of human ASIC3-Δ20 expressed in Xenopus laevis oocytes, but only Hmg 1b-2 inhibited the rat ASIC3 transient current. The Hmg 1b-4 action on rASIC3 as a potentiator was confirmed once again. Both peptides are non-toxic molecules for rodents. In open field and elevated plus maze tests, Hmg 1b-2 had more of an excitatory effect and Hmg 1b-4 had more of an anxiolytic effect on mouse behavior. The analgesic activity of peptides was similar and comparable to diclofenac activity in an acid-induced muscle pain model. In models of acute local inflammation induced by λ-carrageenan or complete Freund's adjuvant, Hmg 1b-4 had more pronounced and statistically significant anti-inflammatory effects than Hmg 1b-2. It exceeded the effect of diclofenac and, at a dose of 0.1 mg/kg, reduced the volume of the paw almost to the initial volume. Our data highlight the importance of a comprehensive study of novel ASIC-targeting ligands, and in particular, peptide toxins, and present the slightly different biological activity of the two similar toxins.

Integration of non-targeted metabolomics with network pharmacology deciphers the anxiolytic mechanisms of Platycladi Semen extracts in CUMS mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms. AIM OF THE STUDY: To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms. MATERIALS AND METHODS: The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen, serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed. RESULTS: Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen. In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the 'neuroactive ligand-receptor interaction' and 'lipid metabolism' were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH). CONCLUSION: This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.

Anxiolytic and Antidepressant Potential of Methanolic Extract of Neurada procumbens Linn. in Mice.

Neurada procumbens Linn. possesses a wide range of phytochemical and bioactive entities such as flavonoids and polyphenols that decrease the oxidative stress and enhance synaptic plasticity, resulting in accelerated healing processes. Almost all parts of the plant have been used in the traditional system of medicine for various disorders including its use as an anticonvulsant, sexual tonic, and anti-rheumatic agent. This study is designed to evaluate the anxiolytic and antidepressant activities of the methanolic crude extract of N. procumbens (Np.Cr) based on its use in traditional medicine and presence of the phytochemical constituents. Aqueous methanolic extract of Np.Cr was prepared under reduced pressure using rotary evaporator, and different chemical constituents were identified by phytochemical screening. Light/dark exploration, elevated plus maze (EPM), and hole board tests were used to assess the anxiolytic activity, while forced swim and tail suspension tests were used to assess the antidepressant potential of the crude extract. Treatment groups treated individually with 3 different doses; i.e., 50, 100, and 200 mg/kg of Np.Cr, showed a dose-dependent increase in time spent in light compartment and in open arms as well as increased number of head poking by the experimental animals. Np.Cr showed significant antidepressant potential (P < .05) as evident from marked decrease in behavioral despair. Findings of the present study assure that N. procumbens possess significant anxiolytic and antidepressant potential with the demands of further investigations to identify the active compound(s) responsible for these pharmacological effects.

Lavandula x intermedia-A Bastard Lavender or a Plant of Many Values? Part II. Biological Activities and Applications of Lavandin.

This review article is the second in a series aimed at providing an in-depth overview of Lavandula x intermedia (lavandin). In part I, the biology and chemistry of lavandin were addressed. In part II, the focus is on the functional properties of lavandin and its applications in industry and daily life. While reviewing the biological properties, only original research articles employing lavandin were considered. Lavandin essential oil has been found to have antioxidant and biocidal activity (antimicrobial, nematicidal, antiprotozoal, insecticidal, and allelopathic), as well as other potential therapeutic effects such as anxiolytic, neuroprotective, improving sleep quality, antithrombotic, anti-inflammatory, and analgesic. Other lavandin preparations have been investigated to a much lesser extent. The research is either limited or inconsistent across all studies, and further evidence is needed to support these properties. Unlike its parent species-Lavandula angustifolia (LA)-lavandin essential oil is not officially recognized as a medicinal raw material in European Pharmacopeia. However, whenever compared to LA in shared studies, it has shown similar effects (or even more pronounced in the case of biocidal activities). This suggests that lavandin has similar potential for use in medicine.

Systematic review on the anxiolytic and hypnotic effects of flower extracts in in vivo pre-clinical studies published from 2010 to 2020.

Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug-drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre-clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: "Animals," "Anxiolytic," "Diazepam," "Elevated Plus Maze," "Flower Extracts," "Insomnia," "In vivo," "Mice," "Open Field Test," "Pre clinical" and "Sedative." The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty-four articles were included, 21 of them performed the animal model of anxiety-like behavior of the elevated plus maze, seven the open field test, and six the light-dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.

Heteroaromatic salvinorin A analogue (P-3 l) elicits antinociceptive and anxiolytic-like effects.

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu1 of µ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization.

[Anxiolytic and antidepressant effects of agarwood inhalation and its mechanism].

This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.