Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80 mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n = 587; placebo, n = 585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p < 0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

Anti-inflammatory effects and related mechanisms in vitro and in vivo of Hedychium coccineum rhizome essential oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedychium coccineum rhizome is an anti-inflammatory ethnomedicine used to remedy inflammation-related swelling and bronchial asthma. AIM OF THE STUDY: The study aimed to analyze the phytochemical constituents of H. coccineum rhizome essential oil (EO) and evaluate its in vitro and in vivo anti-inflammatory effects and underlying mechanisms. MATERIALS AND METHODS: Phytochemical constituents of H. coccineum rhizome EO were analyzed using GC-FID/MS. In RAW264.7 macrophages induced by LPS, blockade of PGE2, NO, IL-1ß, IL-6, and TNF-α secretion by H. coccineum rhizome EO was measured, and then Western blot, qRT-PCR, and immunofluorescent staining were used to evaluate its underlying mechanisms. Moreover, we used the xylene-induced ear edema model for testing anti-inflammatory potential in vivo and examined auricular swelling as well as tissue and serum contents of IL-1ß, IL-6, and TNF-α. RESULTS: EO's main components were E-nerolidol (40.5%), borneol acetate (24.8%), spathulenol (4.5%), linalool (3.8%), elemol (3.5%), and borneol (3.4%). In RAW264.7 cells stimulated by LPS, EO downregulated the expression of pro-inflammatory enzyme (iNOS and COX-2) genes and proteins, thereby suppressing pro-inflammatory mediators (NO and PGE2) secretion. Simultaneously, it reduced TNF-α, IL-1ß, and IL-6 release by downregulating their mRNA expression. Besides, H. coccineum EO attenuated LPS-stimulated activation of NF-κB (by reducing IκBα phosphorylation and degradation to inhibit NF-κB nuclear translocation) and MAPK (by downregulating JNK, p38, and ERK phosphorylation). In xylene-induced mouse ear edema, EO relieved auricular swelling and lowered serum and tissue levels of TNF-α, IL-1ß, and IL-6. CONCLUSIONS: H. coccineum EO had powerful in vivo and in vitro anti-inflammatory effects by inhibiting MAPK and NF-κB activation. Hence, H. coccineum EO should have great potential for application in the pharmaceutical field as a novel anti-inflammatory agent.

Allergic contact dermatitis from essential oil in consumer products: Mode of uses and value of patch tests with an essential oil series. Results of a French study of the DAG (Dermato-Allergology group of the French Society of Dermatology).

OBJECTIVE: To analyse the clinical characteristics and sensitivity of an essential oil patch test series (EOS) in patients sensitized to their own essential oils (EOs). METHOD: We analysed the clinical data and patch test results obtained with the European baseline series (BSE) and an EOS, as well as the mode of use of EOs, through a questionnaire included in the patient file. RESULTS: The study included 42 patients (79% women, average age 50 years) with allergic contact dermatitis (ACD), 8 patients required hospitalization. All patients were sensitized to the EO they used, primarily lavender (Lavandula augustifolia, 8000-28-0), tea tree (Melaleuca alternifolia leaf oil, 68647-73-4), ravintsara (Cinnamomum camphora oil, 92201-50-8), and 2 cases were attributed to helichrysum (helichrysum italicum flower absolute, 90045-56-0). 71% had positive patch tests to fragrance mix I or II, 9 only to the EOS and 4 only with their personal EO. Interestingly, 40% of patients did not spontaneously mention the use of EOs, and only 33% received advice on their use at the time of purchase. CONCLUSION: Patch tests with the BSE, limonene and linalool HP, and oxidized tea tree oil is sufficient to detect most EO-sensitized patients. The most important is to test the patient's own used EOs.

Contact sensitizations in massage therapists with occupational contact dermatitis: Patch test data of the Information Network of Departments of Dermatology, 2008-2020.

BACKGROUND: Massage therapists are particularly exposed to constituents of massage preparations, wet work and mechanical strain and therefore, at high risk to develop occupational dermatitis (OD). OBJECTIVES: To describe the sensitization spectrum of massage therapists with OD. PATIENTS AND METHODS: In a retrospective study, patch test data of patients with OD (128 massage therapists and 24 374 patients working in other professions) collected by the Network of Departments of Dermatology (IVDK, 2008-2020) were analysed. RESULTS: Hand dermatitis (91.4%) and allergic contact dermatitis (34.4%) were common in massage therapists with OD. Most frequent were sensitizations to fragrances/essential oils which were found in 54 (42.2%) massage therapists and thus, more often than in other patients with OD. Concomitant positivity to several fragrances/essential oils was frequent. In 8 (14.8%) of the 54 massage therapists, sensitizations to fragrances/essential oils were not detected with the baseline series, but only with special fragrance series. CONCLUSIONS: Allergic contact dermatitis is common in massage therapists with OD and is mainly caused by fragrances and essential oils. Hence, massage therapists should be aware of this risk. When OD is suspected, not only the baseline series, but also special fragrance series should be patch tested in this occupational group.

Achillea millefolium Essential Oil Mitigates Peptic Ulcer in Rats through Nrf2/HO-1 Pathway.

Extreme ethanol ingestion is associated with developing gastric ulcers. Achillea millefolium (yarrow) is one of the most commonly used herbs with numerous proven pharmacological actions. The goal of the hereby investigation is to explore the gastroprotective action of yarrow essential oil against ethanol-induced gastric ulcers and to reveal the unexplored mechanisms. Rats were distributed into five groups (n = 6); the control group administered 10% Tween 20, orally, for two weeks; the ethanol group administered absolute ethanol (5 mL/kg) to prompt gastric ulcer on the last day of the experiment. Yarrow essential oil 100 or 200 mg/kg + ethanol groups pretreated with yarrow oil (100 or 200 mg/kg, respectively), orally, for two weeks prior to gastric ulcer induction by absolute ethanol. Lanso + ethanol group administered 20 mg/kg lansoprazole, orally, for two weeks prior to gastric ulcer induction by ethanol. Results of the current study showed that ethanol caused several macroscopic and microscopic alterations, amplified lipid peroxidation, pro-inflammatory cytokines, and apoptotic markers, as well as diminished PGE2, NO, and antioxidant enzyme activities. On the other hand, animals pretreated with yarrow essential oil exhibited fewer macroscopic and microscopic modifications, reduced ulcer surface, and increased Alcian blue binding capacity, pH, and pepsin activity. In addition, yarrow essential oil groups exhibited reduced pro-inflammatory cytokines, apoptotic markers, and MDA, restored the PGE2 and NO levels, and recovered the antioxidant enzyme activities. Ethanol escalated Nrf2 and HO-1 expressions, whereas pretreatment of yarrow essential oil caused further intensification in Nrf2 and HO-1. To conclude, the current study suggested yarrow essential oil as a gastroprotective agent against ethanol-induced gastric lesions. This gastroprotective effect could be related to the antioxidant, anti-inflammatory, and anti-apoptotic actions of the essential oil through the instigation of the Nrf2/HO-1 pathway.

Essential Oils Can Mitigate Adverse Effects of Prolonged Masking in the Hospital Setting.

Adverse symptoms of prolonged masking were reported by personnel. A drop of essential oil was added to the mask to mitigate these effects and significantly lessened symptoms. Symptoms declined by almost half, including anxiety, nausea, and indigestion. This simple intervention can mitigate adverse effects of prolonged masking in the hospital setting.

Effect of garlic essential oil in 97 patients hospitalized with covid-19: A multi-center experience.

To observe the synergistic effect of garlic essential oil in patients with novel coronavirus disease (COVID-19), in addition to the routine treatment, we used garlic essential oil in COVID-19 patients with mild to moderate symptoms and compared their results to those of patients who did not receive the essential oil. We conducted a quasi-experimental study with COVID-19 patients from 3 hospitals. In the experimental group, 97 patients received garlic essential oil combined with conventional treatment. In the control group, 100 patients received only the conventional treatment for COVID-19. The effectiveness and safety of the garlic essential oil were assessed. Compared to the control group, the group receiving garlic essential oil showed a shorter duration of symptoms, shorter time to negative nucleic acid testing (NAT) results and shorter time to improvement on the computed tomography (CT). In the same period, the experimental group showed an increase in the rate of the disappearance of symptoms and the improvement rates of NAT and CT. Due to its effectiveness and safety in patients with COVID-19, garlic essential oil is recommended as a preventive measure or a supportive therapy during the COVID-19 pandemic.

Lippia grata essential oil complexed with ß-cyclodextrin ameliorates biochemical and behavioral deficits in an animal model of progressive parkinsonism.

Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.

The fabrication and assessment of mosquito repellent cream for outdoor protection.

Mosquito-borne infections like dengue, malaria, chikungunya, etc. are a nuisance and can cause profound discomfort to people. Due to the objectional side effects and toxicity associated with synthetic pyrethroids, N,N-diethyl-3-methylbenzamide (DEET), N,N-diethyl phenylacetamide (DEPA), and N,N-di ethyl benzamide (DEBA) based mosquito repellent products, we developed an essential oil (EO) based mosquito repellent cream (EO-MRC) using clove, citronella and lemongrass oil. Subsequently, a formulation characterization, bio-efficacy, and safety study of EO-MRC were carried out. Expression of Anti-OBP2A and TRPV1 proteins on mosquito head parts were studied by western blotting. In-silico screening was also conducted for the specific proteins. An FT-IR study confirmed the chemical compatibility of the EOs and excipients used in EO-MRC. The thermal behaviour of the best EOs and their mixture was characterized by thermogravimetric analysis (TGA). GC-MS examination revealed various chemical components present in EOs. Efficacy of EO-MRC was correlated with 12% N,N-diethyl benzamide (DEBA) based marketed cream (DBMC). Complete protection time (CPT) of EO-MRC was determined as 228 min. Cytotoxicity study on L-132 cell line confirmed the non-toxic nature of EO-MRC upon inhalation. Acute dermal irritation study, acute dermal dose toxicity study, and acute eye irritation study revealed the non-toxic nature of EO-MRC. Non-target toxicity study on Danio rerio confirmed EO-MRC as safer for aquatic non-target animals. A decrease in the concentration of acetylcholinesterase (AChE) was observed in transfluthrin (TNSF) exposed Wistar rats. While EO-MRC did not alter the AChE concentrations in the exposed animals. Results from western blotting confirmed that Anti-OBP2A and TRPV1 proteins were inhibited in TNSF exposed mosquitoes. Mosquitoes exposed to EO-MRC showed a similar expression pattern for Anti-OBP2A and TRPV1 as the control group. In silico study revealed eight identified compounds of the EOs play significant roles in the overall repellency property of the developed product. The study emphasizes the mosquito repellent activity of EO-MRC, which could be an effective, eco-friendly, and safer alternative to the existing synthetic repellents for personal protection against mosquitoes during field conditions.

Association of Early Pubertal Onset in Female Rats With Inhalation of Lavender Oil.

BACKGROUND: Central precocious puberty (CPP) is caused by early activation of the hypothalamic-pituitary-gonadal axis but its major cause remains unclear. Studies have indicated an association between chronic environmental exposure to endocrine-disrupting chemicals and pubertal onset. Essential oil is widely used in homes worldwide for relief of respiratory symptoms, stress, and/or sleep disturbance. METHODS: To evaluate this association, we compared the hormone levels and timing of vaginal opening (VO) in female rats exposed to lavender oil (LO) through different routes (study groups: control, LO nasal spray [LS], and indoor exposure to LO [LE]) during the prepubertal period. The body weights of the animals were also compared every 3 days until the day of VO, at which time gonadotropin levels and internal organ weights were assessed. RESULTS: The LS group showed early VO at 33.8 ± 1.8 days compared with the control (38.4 ± 2.9 days) and LE (36.6 ± 1.5 days) groups. Additionally, luteinizing hormone levels were significantly higher in the LE and LS groups than those in the control group. Body weights did not differ significantly among the groups. CONCLUSION: Inhalation exposure to an exogenic simulant during the prepubertal period might trigger early pubertal onset in female rats. Further evaluation of exposure to other endocrine-disrupting chemicals capable of inducing CPP through the skin, orally, and/or nasally is warranted.

Topical Cyperus rotundus essential oil for treatment of axillary hyperpigmentation: a randomized, double-blind, active- and placebo-controlled study.

BACKGROUND: The oil of the grass Cyperus rotundus (purple nutsedge) is an effective and safe treatment option for a variety of conditions. It has anti-inflammatory and antipigmenting properties. There have been no clinical trials comparing topical C. rotundus oil with skin-lightening treatments for axillary hyperpigmentation. AIM: To assess the efficacy of C. rotundus essential oil (CREO) in treating axillary hyperpigmentation, and compare with another active treatment hydroquinone (HQ) and a placebo (cold cream) in this study. METHODS: The study included 153 participants, who were assigned to one of three study groups: CREO, HQ group or placebo group. A tri-stimulus colorimeter was used to assess pigmentation and erythema. Two independent experts completed the Physician Global Assessment, and the patients completed a self-assessment questionnaire. RESULTS: CREO had significantly (P < 0.001) better depigmenting effects than HQ. CREO and HQ did not differ significantly in terms of depigmentation effects (P > 0.05); however, there were statistically significant differences in anti-inflammatory effects and decrease in hair growth (P < 0.05) in favour of CREO. CONCLUSIONS: CREO is a cost-effective and safe treatment for axillary hyperpigmentation.

Essential oils as anticancer agents: Potential role in malignancies, drug delivery mechanisms, and immune system enhancement.

Cancer retains a central place in fatality rates among the wide variety of diseases known world over, and the conventional synthetic medicaments, albeit used until now, produce numerous side effects. As a result, newer, better, and safer alternatives such as natural plant products, are gravely required. Essential oils (EOs) offer a plethora of bioactivities including antibacterial, antiviral, antioxidant, and anticancer properties, therefore, the use of EOs in combination with synthetic drugs or aromatherapy continues to be popular in many settings. In view of the paramount importance of EOs and their potential bioactivities, this review summarizes the current knowledge on the interconnection between EOs and cancer treatment. In particular, the current review presents an updated summary of the chemical composition of EOs, their current applications in cancer treatments based on clinical studies, and the mechanism of action against the cancer cell lines. Similarly, an overview of using EOs in aromatherapy and enhancing immunity during cancer treatment is provided. Further, this review focuses on the recent technological advancements such as the loading of EOs using protein microspheres, ligands, or nanoemulsions/nanoencapsulation, which offer multiple benefits in cancer treatment via site-specific and target-oriented delivery of drugs. The continuing clinical studies of EOs implicate that their pharmacological applications are a rewarding research area.

Anti urolithiatic activity of Cyperus rotundus tubers: In silico, In vitro and In vivo approaches

Abstract The present research evaluated the anti urolithic potential of Cyperus rotundus tubers extract using in silico, in vitro and in vivo techniques. In silicostudy was performed of Cyperus rotundus constituents and pathological protein oxalate oxidase (PDB Id: 2ETE). In vitrostudy, nucleation and aggregation assay involved for assessment of ethanol extract of Cyperus rotundus tuber (50-3000 µg/ml).In vivo studies involved that the Cyperus rotundusethanolic extract (100, 200 and 400 mg/kg B.wt.) wastreatedonsodium oxalate induced urolithiatic rats for seven days,evaluated kidney function by urine and serum biochemical analysis and statistical analysis performed usingGraphPad prism5 software.In silico results showedthat Cyperus rotundus constituents,Humulene epoxide, 4-Oxo-alpha-ylangene, Cubebol were exhibited better binding energyonoxalate oxidase.Ethanolic extract of Cyperus rotundustuber was exhibited nucleation, aggregation of calcium oxalate monohydrate crystals inhibition in dosedependent manner. Sodium oxalate treatment was triggered biochemical changesin the urine that have been substantially prevented by the ethanolic extract of Cyperus rotundus tuber. The current findings Cyperus rotundus anti urolithic activity due to antioxidant essential oils. The molecular docking results could be used to optimize lead and develop the appropriate urolithiasis treatment.

Composición química y actividad antimicrobiana del aceite esencial de Minthostachys mollis frente a patógenos orales / Chemical composition and antimicrobial activity of essential oil from Minthostachys mollis against oral pathogens

Introduction: Minthostachys mollis is medicinal plant frequently used because of its anti-inflammatory and antibacterial properties. Objective: Identify the chemical composition of the essential oil from Minthostachys mollis and evaluate its antimicrobial properties against oral pathogens. Methods: The essential oil was extracted from the fresh leaves and branches of the plant by steam distillation method, and Gas Chromatography-Mass Spectrometry were performed to identify the principal constituents of the essential oils. Repetitions for the antimicrobial assay were calculated with the Epi info TM program. The antimicrobial activity was tested against Enterococcus faecalis ATCC 29212, Porphyromonas gingivalis ATCC 33277 and Candida albicans ATCC 10231 by disc diffusion assay and microdilution method, the minimum inhibitory concentration, minimum bacterial concentration and minimum fungal concentration were recorded. Results: The main compounds found were menthone (32.9 percent) and eucalyptol (28.1 percent). The essential oil of M. mollis demonstrated inhibition zones against E. Faecalis, P. gingivalis and C. albicans of 15.13 ± 0.39, 17.96 ± 0.21, and 20.82 ± 0.63 mm, respectively. There were significant differences on the inhibition zones between the three strains tested, being C. albicans the most sensible microorganism (p < 0.05). The minimum inhibitory concentration ranged from 1.05 to 2.11 µg/mL, the minimum bacterial concentration ranged from 2.11 to 4.23 µg/mL, and the minimum fungal concentration was 1.05 µg/mL. Conclusions: The essential oil of Minthostachys mollis showed as principal compounds menthone and eucalyptol and it has an important antimicrobial activity against E. faecalis, P. gingivalis and C. albicans(AU)

Introducción: Minthostachys mollis es una planta medicinal de uso frecuente por sus propiedades antiinflamatorias y antibacterianas. Objetivo: Identificar la composición química del aceite esencial de Minthostachys mollis y evaluar sus propiedades antimicrobianas frente a patógenos orales. Métodos: El aceite esencial se extrajo de las hojas y ramas frescas de la planta mediante el método de destilación al vapor; se realizó una cromatografía de gases-espectrometría de masas para identificar los principales constituyentes del aceite esencial. Las repeticiones del ensayo antimicrobiano se calcularon con el programa Epi infoTM. La actividad antimicrobiana se evaluó frente a Enterococcus faecalis ATCC 29212, Porphyromonas gingivalis ATCC 33277 y Candida albicans ATCC 10231 mediante ensayo de difusión en disco y método de microdilución. Se registró la concentración mínima inhibidora, la concentración mínima bactericida y la concentración mínima fungicida. Resultados: Los principales compuestos encontrados fueron mentona (32,9 por ciento) y eucaliptol (28,1 por ciento). El aceite esencial de M. mollis generó zonas de inhibición frente a E. Faecalis, P. gingivalis y C. albicans de 15,13 ± 0,39, 17,96 ± 0,21 y 20,82 ± 0,63 mm, respectivamente. Existió diferencias significativas en las zonas de inhibición entre las tres cepas, siendo C. albicans el microorganismo más sensible (p < 0,05). La concentración mínima inhibitoria varió de 1,05 a 2,11 µg/mL, la concentración mínima bacteriana varió de 2,11 a 4,23 µg/mL y la concentración mínima de hongos fue 1,05 µg/mL. Conclusiones: El aceite esencial de Minthostachys mollis mostró como compuestos principales mentona y eucaliptol y posee una importante actividad antimicrobiana contra E. faecalis, P. gingivalis y C. albicans.

Patch testing to plants: sensitisation associated with exposure to plants, essential oils and botanicals in cosmetics.

BACKGROUND: Contact allergy to plants, particularly Compositae, presents with dermatitis and is diagnosed with skin patch testing. Sesquiterpene lactone mix is a common screening allergen for plant allergy. The rate of plant allergen sensitisation in New Zealand, which is affected by local horticultural factors, has not previously been documented. AIMS: To investigate the rate of plant allergen sensitisation in New Zealand's regional population, characterise common allergens and reassess appropriate allergens for patch testing. METHODS: Retrospective analysis of patient demographics and patch-test results over an eight-year period (2012 to 2020) was performed at a tertiary patch-test clinic in Auckland, New Zealand. RESULTS: 820 patients completed patch testing. There was a 12.9% sensitivity rate (a positive reaction on patch testing) to at least one plant allergen and a 6.2% plant allergy rate (positive reaction of current relevance). The most frequent positive reactions were Myroxylon pereirae (n=38), colophonium (n=35) and sesquiterpene lactone mix (n=14). Of patients with a plant allergy (n=51), the allergy source was a botanical in a cosmetic product in 27 cases (52.9%), a plant in ten (19.6%) and an essential oil in two (3.9%). CONCLUSIONS: Reactions to plant allergens were related to botanicals in cosmetics and creams, plants and essential oils. Rates of plant sensitisation in our cohort are comparable with international data.

Oral gel loaded with penciclovir-lavender oil nanoemulsion to enhance bioavailability and alleviate pain associated with herpes labialis.

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.