Pharmacokinetic interactions between natural extracts and hepatic cytochrome P450 (CYP) enzymes are a concern in veterinary medicine. Lavender essential oil (LEO), containing linalool (LIN) and linalyl acetate (LINAc), may be coadministered with conventional medicines. This study examined the canine metabolism of LIN and LINAc by substrate depletion using pooled dog liver microsomes (pDLMs) and recombinant canine CYP enzymes (rCYPs). Inhibitory effects of LIN, LINAc, and LEO on CYP isoform-selective probe drug reactions were also evaluated. LINAc was hydrolysed to LIN by a heat-sensitive esterase activity in pDLMs. LIN depletion by pDLMs was NADPH-dependent, saturable with a Michaelis-Menten constant of 52 ± 11 µM, and induced by over 5-fold in liver microsomes from phenobarbital-treated dogs. Recombinant CYP2B11 showed the highest LIN depletion activity, followed by CYP2C21, while other CYPs tested did not show measurable substrate depletion. Inhibition experiments showed that LIN, LINAc, and LEO inhibited CYP2B11-mediated metabolism but not metabolism by CYP2C21, CYP2D15, or CYP3A12. IC50 values for LIN, LINAc, and LEO were 7.1, 2.7, and 2.5 µM for tramadol N-demethylation, and 13.9, 8.0, and 8.6 µM for methadone-N-demethylation, respectively. None of the terpenes were shown to directly inhibit recombinant CYP2B11 activity, suggesting that they exerted indirect inhibition via metabolites generated by other CYPs in pDLMs. These findings highlight CYP2B11 and CYP2C21 as key enzymes in LIN and LINAc metabolism and underscore the potential for herb-drug interactions when treating dogs with lavender essential oil.

Pd-Te alloy inside hollow silica nanospheres for semi‑hydrogenation of dehydrolinalool to linalool.

Chitosan-ε-polylysine‑sodium tripolyphosphate based Pickering emulsions for co-encapsulation of cinnamaldehyde and linalool: An effective sustained-release system against toxigenic fungi.

Rifampicin (RF) is a primary anti-tuberculosis medication utilized in tuberculosis treatment, and its concurrent administration with other medications, as well as the duration of therapy, may result in adverse effects. While the hepatotoxicity of RF is established, its impact on the spleen remains unexamined. Thus, our study aimed to investigate the impact of RF on the spleen and the protective role of Linalool (LN), a monoterpene, through the Heme oxygenase-1 (HO-1) enzyme pathway, with biochemical analyses, oxidative stress parameters, protein levels, and histopathological assessments. In the study, thirty healthy adult male Sprague-Dawley rats were randomly allocated into five groups: control, solvent control (dimethyl sulfoxide - DMSO), RF, LN, and RF + LN. Spleen tissues and blood specimens were collected from the rats for examination. RF markedly elevated total and indirect bilirubin, Fe2+, HO-1, and MDA levels, while diminishing GSH levels. Conversely, in the RF + LN group, total and indirect bilirubin, Fe2+, HO-1, and MDA levels were dramatically reduced, whereas GSH levels were elevated. Histopathologically, RF-induced defects were ameliorated in the LN-treated cohorts. In conclusion, rifampicin exhibited toxic effects on the spleen, which were mitigated by LN.

Background: Arterial hypertension (AH) remains a global health concern due to its multifactorial etiology, limited therapeutic success, and high cardiovascular risk. In this context, plant-derived compounds such as essential oils have gained attention as alternative strategies. The monoterpene (-)-linalool (LIN) demonstrates antihypertensive effects. However, its clinical application is hampered by poor solubility and low bioavailability. Methods: This study aimed to investigate the chronic cardiovascular effects of free LIN and its inclusion complex with β-cyclodextrin (LIN/β-CD) in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. Results: Pharmacokinetic analysis showed that complexation with β-CD markedly improved LIN plasma exposure, increasing systemic bioavailability by approximately 20-fold and prolonging its circulation time. In acute assays, intravenous LIN and LIN/β-CD (50 mg/kg) reduced blood pressure in SHR, LIN induced bradycardia, and LIN/β-CD elicited a mild, non-significant tachycardia. Orally administered LIN/β-CD exerted superior antihypertensive effects compared to free LIN. In a 60-day chronic regimen, LIN/β-CD consistently maintained reduced arterial pressure, achieving levels comparable to normotensive controls, while free LIN produced transient effects. LIN/β-CD also significantly reduced the cardiac mass index in SHR, suggesting attenuation of hypertrophic remodeling. Vascular reactivity assays revealed enhanced endothelium-dependent and -independent relaxation and diminished vasoconstriction in LIN/β-CD-treated animals, indicating improved endothelial and smooth muscle function. Histological analyses confirmed the absence of cardiac or vascular injury in both treatment groups. Conclusions: In conclusion, the LIN/β-CD complex improves the pharmacokinetic profile and enhances the arterial morphology, antihypertensive and cardioprotective effects of linalool. These findings support its translational potential as a safe and effective oral formulation for the long-term management of hypertension and associated cardiovascular dysfunction.

1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) molecular layer with the addition of trans-2-nonenal (NE) as a simple experimental model of epithelial cellular membrane damaged by malodorous substance was investigated to elucidate the masking effect of odorants (benzaldehyde (BA), methyl benzoate (MB), phenyl acetate (PA), linalool (LL), dihydromyrcenol (DM), tetrahydrolinalool (TL), and 3,7-dimethyl-1-octene (DO)). As for the surface pressure (Π)-area (A) isotherm of the DOPC monolayer, A at Π for the DOPC monolayer including NE were decreased by the aromatic compounds with electron-withdrawing substituents (BA, MB) in comparison with that with electron-donating substituent (PA). The decreases in A with the addition of acyclic terpenes with both double bonds and OH group (LL, DM) were larger than those with either double bond or OH groups (TL, DO). Similar trends to the changes in A of the Π-A isotherms were obtained in the peaks of the wavenumbers in Fourier transform infrared spectroscopy arising from the PO2 - asymmetric stretching vibration mode of DOPC with the addition of NE and the odorants. These results suggest that odorants with the aromatic ring with electron-withdrawing substituent are easily eliminated from the DOPC membrane together with NE as the masking effect, rather than the aromatic ring with electron-donating substituent.

For test substances with unfavorable physicochemical properties, different pathways of substance depletion such as volatilization or sorption to polymers or serum constituents can decrease the bioavailable fraction during in vitro toxicity testing. If not accounted for, this can lead to underestimated toxicity or even false-negative results. Therefore a thorough understanding of the in vitro test system as well as potential pitfalls and analytical confirmation of substance concentrations are required for reliable results. Here, we investigated the genotoxicity of the monoterpenes (R)-(+)-limonene (RLIM) and β-myrcene (βMYR), the monoterpene alcohol (±)-linalool (LIN) and the known volatile mutagen 1-bromopopane (1-BP) in the mouse lymphoma assay (MLA) and quantified the exposure concentrations. Additionally, a headspace (HS)-free incubation setup is presented which allows for sufficient exposure of suspension cells with volatile test substances. RLim, βMYR and 1-BP, showed rapid and quantitative evaporation during incubation, potentially confounding the outcome of the genotoxicity test which could be minimized in the HS-free incubation setup. Furthermore, extensive binding of RLIM and βMYR to serum constituents was shown to decrease bioavailability during HS-free incubation. While the HS-free incubation setup increased the sensitivity of the MLA for volatile genotoxins, no signs for mutagenicity were observed for the monoterpenes, underscoring their safety.

Coriandrum sativum L. is well known for its usage in traditional medicine and cooking. This herb is commonly known as coriander as well as cilantro. C. sativum possesses many important phytochemical groups, including polyphenols, vitamins, and phytosterols, with promising biological activities such as antioxidant, anti-inflammatory, anticancer, anti-antidiabetic, neuropharmacological, and so on. This study aimed to assess the membrane-stabilizing and clot-lysis capacity of C. sativum ethanol extract (ECS) and its major component, linalool (LIN). In-vitro membrane-stabilizing action of ECS and LIN was performed by using hemolysis of human red blood cells (HRBCs) and egg albumin protein denaturation techniques, and clot lysis activity was observed by human clotted blood techniques. Further, we observed in-silico studies. ECS and LIN showed significant (p < 0.05) membrane-stabilizing and clot-lysing capacity compared to the control group in a concentration-dependent manner. The highest inhibition of hemolysis by the ECS was observed at 160 µg/mL by 77.61 ± 0.01%, while LIN demonstrated 52.32 ± 0.01%. Further, in the egg-albumin protein denaturation test, ECS and LIN demonstrated 27.62 ± 0.01% and 46.74 ± 0.02% membrane protection, respectively. At 160 µg/mL, ECS and LIN showed clot lysis activity of 18.02 ± 3.968% and 52.32 ± 0.01%, respectively. In our in-silico studies, LIN exhibited significant binding interactions with different inflammatory mediators and clot lysis factors. ECS showed strong membrane-stabilizing and moderately clot-lysing activity in our studies, and it may be possible due to the presence of the major component LIN.

The advancement of Antimicrobial Resistance (AMR) and the lack of effective treatments demand the development of new drugs to combat resistant bacteria. Plants, in turn, produce various Secondary Metabolites (SMs) with diverse molecular structures, which are promising therapeutic alternatives. This study aims to evaluate the potential of 13 plant derived SMs in modulating bacterial resistance to amoxicillin (AMO), and to investigate the mechanisms of action against Staphylococcus aureus (ATCC 29213) and Klebsiella pneumoniae (UFPDA 396) using Molecular Docking (MD) simulations. Among the tested SMs, p-Cymene (CYM) showed the best activity against S. aureus, with a Minimum Inhibitory Concentration (MIC) of 512µg/mL, while Eugenol (EUG) was most effective against K. pneumoniae, with an MIC of 1024µg/mL. In resistance modulation assays using the checkerboard method, SMs including EUG, CYM, α-pinene (APN), β-pinene (BPN), Geraniol (GER), Linalool (LNL), and Myrcene (MYR) exhibited synergistic effects when combined with AMO, with Fractional Inhibitory Concentration Index (FICI) values ranging from 0.1 to 0.5. Additionally, both the SMs and AMO, as well as their synergistic combinations, were docked to molecular targets associated with resistance and virulence in S. aureus and K. pneumoniae. The drug-protein complexes showed favorable interaction energies, confirming that the binding free energy of the synergistic combinations was superior to that of the individual compounds. Overall, the most significant differences in activity between combined and isolated treatments were observed for MurD in S. aureus and SidA in K. pneumoniae. These findings suggest that SMs may serve as potential candidates for the development of synergistic or additive molecules to be used alongside conventional antibiotics, representing a promising strategy to mitigate AMR and offer viable and effective therapeutic alternatives.

Linalool (LIN), a naturally occurring monoterpene alcohol found in aromatic plants, exhibits diverse pharmacological properties, yet its antiemetic potential remains underexplored. In this study, we investigated the antiemetic efficacy of LIN using both in vivo and in silico approaches. Emesis was induced in chicks via oral administration of copper sulfate pentahydrate (50mg/kg), and LIN was tested at doses of 25, 50, and 100mg/kg. Its effects were compared against the standard antiemetics domperidone (DOM, 7mg/kg) and ondansetron (OND, 5mg/kg). Results demonstrated that LIN at 100mg/kg significantly prolonged the emetic latency and reduced the number of retches. Notably, co-administration of LIN (50mg/kg) with DOM significantly (p < 0.05) produced the most potent effect, yielding the highest latency and lowest number of retches, reflecting a synergistic interaction. Molecular docking studies revealed a strong binding affinity of LIN to the dopamine D2 receptor (- 6.4kcal/mol) and moderate binding to the 5-HT3 receptor (- 5.3kcal/mol), suggesting involvement of both dopaminergic and serotonergic mechanisms. These findings collectively indicate that LIN possesses significant antiemetic activity and may offer a plant-derived alternative for emesis control.

N icotine, the principal addictive compound in tobacco, exerts widespread metabolic toxicity, including oxidative stress, mitochondrial dysfunction, amino acid and lipid derangements, and inflammatory damage to vital organs. Despite the clinical use of varenicline tartrate (VT) as a smoking cessation drug, its therapeutic effects on nicotine-induced metabolic dysfunction remain underexplored. Plant-derived phytochemicals such as linalool (LL) and methyl eugenol (ME), known for their antioxidant and anti-inflammatory properties, may offer comparable or superior protective effects as compared to that of VT. This study is aimed at evaluating and comparing the therapeutic efficacy of LL and ME with VT in attenuating nicotine-induced metabolic, biochemical, and histopathological abnormalities using integrated GC-MS and ESI-MS/MS-based metabolomics. Biochemical markers (ALT, AST, IL-6, TNF-α, MDA); histopathological analysis of hepatic, renal, and pulmonary tissues; and plasma metabolomic profiling using GC-MS and ESI-MS/MS were assessed in nicotine-exposed rats treated with LL, ME, and/or VT. Nicotine exposure significantly increased ROS, inflammatory cytokines, and liver enzymes while disrupting amino acid (glutamate) and lipid (LPCs, carnitines) metabolism. Histologically, nicotine caused hepatocellular vacuolation, renal tubular damage, and pulmonary congestion. Both LL and ME significantly reduced oxidative stress and inflammation, normalized glutamate levels, and restored tissue integrity. LL showed superior hepatoprotective and glutamate-restoring effects, while ME more effectively downregulated COX-2 and TNF-α. VT, although effective in reducing inflammatory markers, showed limited ability to reverse glutamate depletion or normalize lipid metabolic profiles. Unlike ME and LL, VT provided moderate histological recovery but failed to fully ameliorate tissue damage. GC-MS highlighted lipid metabolite abnormalities (e.g., LPCs, fatty acids), whereas ESI-MS/MS revealed significant reductions in oleamide and glutamate, confirming broader metabolic disruption and the superior recovery effects in LL and ME groups compared to VT. LL and ME exhibited greater therapeutic potential than VT in restoring metabolic balance and protecting against nicotine-induced organ damage. The ability of ME and LL to correct both lipid and amino acid metabolism positions them as promising natural alternatives or adjuncts for managing nicotine-associated metabolic dysfunction.

Background: Cytochrome P450 (CYP450) enzymes play a central role in the metabolism of xenobiotics, including plant-derived compounds such as terpenoids. Objectives: This study aimed to predict the molecular interactions of linalool (LIN) and linalyl acetate (LINAct), major constituents of lavender essential oil, with the canine CYP2B11, CYP2C21, and CYP2D15 isoforms, using in silico approaches. Methods: Three-dimensional (3D) models of the target enzymes were generated through homology modeling using SWISS-MODEL and validated based on global model quality estimate (GMQE) and QMEAN Z-score metrics. Ligand structures were optimized in the Molecular Operating Environment (MOE), and pharmacophoric features were analyzed. Molecular docking simulations were performed using AutoDock Vina, followed by visualization of interactions in MOE. Results: LIN and LINAct exhibit favorable binding affinities with all three isoforms, suggesting their potential as substrates or modulators. Hydrogen bonding and hydrophobic interactions were the predominant forces stabilizing the ligand–enzyme complexes. Conclusions: These findings provide a computational basis for understanding the hepatic metabolism of LIN and LINAct in dogs, offering preliminary insights into the role of specific CYP isoforms in their biotransformation.

The increasing antimicrobial resistance, particularly in Acinetobacter baumannii, complicates the treatment of infections, leading to higher morbidity, mortality, and economic costs. Herein, we aimed to determine the in vitro antimicrobial, synergistic, and antibiofilm activities of colistin (COL), meropenem, and ciprofloxacin antibiotics, and curcumin, punicalagin, geraniol (GER), and linalool (LIN) plant-active ingredients alone and in combination against 31 multidrug-resistant (MDR) A. baumannii clinical isolates. The combinations were tested to identify alternative approaches to conventional antibiotic therapy by reducing the Minimum Inhibitory Concentration (MIC) values of antibiotics when used with plant-active ingredients. Synergistic interactions were evaluated by checkerboard assay and interpreted via the Fractional Inhibitory Concentration Index (FICI). Antibiofilm activity was assessed using crystal violet microtiter plate method. Notably, COL with GER (83.87%) and with LIN (77.42%) exhibited strong synergistic interactions, with FICI values between 0.12 and 0.5. Where synergism was observed, antibiotic MICs were reduced by 2- to 128-fold, indicating substantial enhancement in bacterial efficacy. Synergistic and additive interactions were more prevalent than indifference, and no antagonism was detected. Biofilm formation inhibition assays further demonstrated that these combinations significantly suppressed biofilm production in A. baumannii isolates. Biofilm eradication rates were consistently highest at 2×MIC concentrations for all tested antibiotics and plant-active ingredients. Cytotoxicity tests on L929-fibroblast cell lines confirmed the safety at the tested concentrations. Combining conventional antibiotics with plant-active ingredients offers a novel approach to mitigating the impact of MDR A. baumannii.

Bioactive films with essential oils and machine learning for controlling Aspergillus niger growth and fumonisin B2 production in vitro.

The displacement of fossil fuel use for transport with sustainable alternatives is urgently required to reduce greenhouse gas emissions and address global climate change. Advanced biofuels from renewable feedstocks, for example waste biomass, present an opportunity to decarbonise the use of combustion for propulsion however sustainable utilisation of these fuels also requires consideration of impacts on other exhaust pollutants that negatively affect the environment and human health. Therefore, while exhaust after-treatment systems are an established and effective means of emission reduction during combustion of hydrocarbon fuels, there is a need to understand impacts of biofuel use on the performance of devices including three-way catalysts (TWC) for simultaneous reduction of nitrogen oxides (NOx), carbon monoxide (CO) and unburnt hydrocarbons (THC). This experimental study therefore investigates the effects of four potential biofuel molecules, 2-methylfuran (MF), 2-methyltetrahydrofuran (MTHF), gamma valerolactone (GVL) and linalool (LNL), on combustion, engine-out exhaust emissions and pollutant conversion across a three-way catalyst (TWC) in a gasoline direct-injection engine. The potential biofuel molecules were blended with reference gasoline (RGL) at 20% wt/wt and supplied to a light-duty direct-injection spark ignition engine operated at constant conditions, with gaseous and particulate exhaust emissions measured pre- and post- TWC during catalyst warm-up during engine cold-start and at steady state. While the biofuel blends displayed similar rates of heat release rate relative to gasoline combustion, the MF blend significantly increased CO and NOx engine-out emissions both during cold-start and at steady state. The use of GVL reduced NOx, while hydrogen (H 2 ) emissions correlated with blend hydrogen carbon ratio. All of the biofuel blends increased the TWC inlet temperature required for pollutant conversion, while MF, LNL and GVL increased H 2 levels post-TWC at higher temperatures. LNL exhibited higher particulate levels post-TWC than gasoline only, despite lower engine-out emissions during combustion of the biofuel blend.

Multi-drug-resistant (MDR) pathogens pose a significant global health challenge, underscoring the urgent need for novel antimicrobial agents with minimal toxicity to humans. This study investigated the in vitro and in silico antimicrobial and antibiofilm potentials of four essential oils (EOs): clove bud oil (CBO; Syzygium aromaticum L.), black seed oil (BSO; Nigella sativa L.), cinnamon bark oil (CNBO; Cinnamomum zeylanicum), and citronella oil (CTLO; Cymbopogon nardus L.), against 19 selected human pathogens, including MDR strains. Among the tested EOs, CBO, BSO, and CNBO exhibited the highest antibacterial activity against Staphylococcus epidermidis, with the mean zone of inhibition diameters (ZIDs) of 20.0 ± 0.2 mm, 46.0 ± 0.3 mm, and 32.0 ± 0.1 mm, respectively, at a concentration of 10 µL/disc, while CTLO displayed no antibacterial activity. CNBO demonstrated superior antifungal activity, with the mean ZIDs of 49.0 ± 0.3 mm and 36.0 ± 0.3 mm for Candida albicans and Aspergillus niger, respectively. Molecular docking analyses revealed robust interactions of key bioactive compounds—eugenol (EU) from CBO, thymoquinone (TQ) from BSO, cinnamaldehyde (CN) from CNBO, citronellal (CIT) and linalool (LIN) from CTLO—with microbial target proteins, substantiating their antimicrobial and antibiofilm potential. Notably, CTLO, despite limited in vitro activity, exhibited unique binding interactions in silico, suggesting potential niche applications. These findings underscore the translational potential of EOs as alternative antimicrobial therapies against MDR infections, particularly biofilm-associated infections, and highlight the need for further in vivo studies to validate their efficacy and safety.

Multi-drug-resistant (MDR) pathogens pose a significant global health challenge, underscoring the urgent need for novel antimicrobial agents with minimal toxicity to humans. This study investigated the in vitro and in silico antimicrobial and antibiofilm potentials of four essential oils (EOs): clove bud oil (CBO; Syzygium aromaticum L.), black seed oil (BSO; Nigella sativa L.), cinnamon bark oil (CNBO; Cinnamomum zeylanicum), and citronella oil (CTLO; Cymbopogon nardus L.), against 19 selected human pathogens, including MDR strains. Among the tested EOs, CBO, BSO, and CNBO exhibited the highest antibacterial activity against Staphylococcus epidermidis, with the mean zone of inhibition diameters (ZIDs) of 20.0 ± 0.2 mm, 46.0 ± 0.3 mm, and 32.0 ± 0.1 mm, respectively, at a concentration of 10 µL/disc, while CTLO displayed no antibacterial activity. CNBO demonstrated superior antifungal activity, with the mean ZIDs of 49.0 ± 0.3 mm and 36.0 ± 0.3 mm for Candida albicans and Aspergillus niger, respectively. Molecular docking analyses revealed robust interactions of key bioactive compounds-eugenol (EU) from CBO, thymoquinone (TQ) from BSO, cinnamaldehyde (CN) from CNBO, citronellal (CIT) and linalool (LIN) from CTLO-with microbial target proteins, substantiating their antimicrobial and antibiofilm potential. Notably, CTLO, despite limited in vitro activity, exhibited unique binding interactions in silico, suggesting potential niche applications. These findings underscore the translational potential of EOs as alternative antimicrobial therapies against MDR infections, particularly biofilm-associated infections, and highlight the need for further in vivo studies to validate their efficacy and safety.

Cyclophosphamide (CP) is associated with detrimental side effect including hepatic and renal toxicities. Linalool (LIN), acyclic monoterpene alcohol, is acquired from several plants' essential oils. Rats were disseminated into four groups. Group 1: Normal and Cyclophosphamide (CP) groups in which rats were given normal saline or CP intraperitoneally (200 mg/kg, ip on 12nd). Group 3 and 4 (LIN 50 + CP and LIN 100 + CP) groups in which rats were administered LIN (50 or 100 mg/kg) orally for 14 days and CP (200 mg/kg, ip on 12nd). Assessment of hepatic and renal function tests and histopathological examination were performed. Oxidative stress indicators, inflammatory mediators, and apoptosis markers in hepatic and renal homogenates were assessed. JAK2/STAT3/NFκB gene expression was measured. The network pharmacology study suggests JAK2 as one the targets so molecular docking of LIN against JAK2 was accomplished. LIN administration with CP resulted in a significant reduction in liver function test including ALT, AST, LDL, bilirubin, and γGTT1 and in renal function markers including BUN, creatinine, uric acid, Kim-1, NGAL, and CysC. Also, LIN increases in antioxidant ability via enhancing GST, GSH-Px, GSH-R, SOD, and catalase as well as a declining NO, MDA levels. Furthermore, LIN significantly diminished JAK2/STAT3/NFκB gene expressions with subsequent reduction in the inflammatory markers including TNF-α, MPO, ICAM-1, IL-6, and IL-1β levels and the apoptotic markers Bax and cleavage caspase-3 and 9. LIN protected the hepatic and renal tissues from ROS damage and mitigated JAK2/STAT3/NFκB with subsequent anti-inflammatory and anti-apoptotic properties.

Linalool (LIN) has some important neuropharmacological activities, including anxiolytic and sedative effects. It is also clear that it protects experimental animals from convulsions and Alzheimer's disease. On the other hand, caffeine (CAF) and sclareol (SCL) have neurostimulatory potential. This study evaluates the sedative effect and possible molecular mechanisms of CAF with LIN and/or SCL through in vivo and in silico studies. For this, CAF (10mg/kg) alone or with LIN (50mg/kg) and/or SCL (10mg/kg) was intraperitoneally (i.p.) treated before thirty minutes of thiopental sodium (TS) injection (40mg/kg, i.p.) to the mice and observed for latency and duration of sleep up to 4h. To understand the possible action mechanisms of these drugs, we also performed molecular docking and pharmacokinetics profile studies with gamma-aminobutyric acid (GABAA) receptor respective subunits. Findings suggest that LIN exerted significant (p < 0.05) sedative effects on the animals. CAF and SCL alone or in their combinations significantly reduced LIN's effects in mice. CAF, LIN, and SCL showed binding affinities of ‒6.2, ‒5.5, and ‒7.3kcal/mol with 6X3X of the GABAA receptor (α1 and β2 subunits), respectively. Taken together, LIN exerted significant sedative effects, whereas CAF and SCL, either alone or in combination, attenuated this effect in mice. These findings suggest that LIN, CAF, and SCL modulate sedation through interactions with the GABAA receptor pathway. Further clinical studies are required to confirm these results.

Linalool (LIN), a monoterpene alcohol from lavender and coriander essential oils, is known for its anti-inflammatory and analgesic properties. However, its potential in arthritis management, combining in vitro, in vivo, and in silico studies; pharmacokinetics; and toxicity management, remains unexplored. This study investigated LIN's anti-arthritis activity through various approaches: in vitro (egg albumin test), in vivo (terpene oil, formaldehyde-induced, and Freund's complete adjuvant (FCA)-induced models), and in silico analyses. In the in vivo study, LIN (25, 50, and 75 mg/kg, p.o.) and the combination of LIN-50 with indomethacin (INDO, 10 mg/kg, p.o.) were evaluated. LIN-75 significantly reduced paw licking, inhibited paw edema in the terpene oil and formaldehyde-induced models, and showed significant inhibition in the FCA-induced arthritis model. The combination therapy of LIN-50 + INDO-10 demonstrated enhanced anti-arthritis activity compared to individual treatments. In the in vitro egg albumin test, LIN-75 exhibited the highest membrane-stabilizing activity, and its combination with INDO-10 resulted in a synergistic effect. In silico studies revealed significant binding affinities of LIN with COX-1, COX-2, and TNF-α (-5.5, -5.1, and -5.0 kcal/mol, respectively), suggesting its potential mechanism of action. Additionally, LIN showed favorable pharmacokinetics with lower toxicity than INDO. In conclusion, LIN exhibited dose-dependent anti-arthritic effects across various models, highlighting its potential as a therapeutic agent for rheumatoid arthritis (RA). Its efficacy suggests promising clinical relevance, warranting further research on its pharmacokinetics, toxicity management, and clinical applicability to fully establish its therapeutic benefits.