Volatile Oil of Magnolia biondii Pamp. for Transnasal Administration: Its Preparation, Characterization, And Mechanism of Action in the Treatment of Allergic Rhinitis.

BACKGROUND: Allergic Rhinitis (AR) is a common chronic nasal condition usually caused by allergens. The immune system overreacts when the body is exposed to allergens, releasing a lot of tissue chemicals that cause congestion, more secretions, and an inflammatory reaction in the nasal mucosa. METHOD: In clinical practice, it remains a significant public health issue. Modern pharmacological studies have demonstrated that Magnolia Volatile Oil (MVO) has good anti-inflammatory, antibacterial, immunomodulatory, and other pharmacological effects. Previous research and literature reports have reported that MVO has good therapeutic effects on allergic rhinitis. However, due to the poor water solubility of Magnolia, its bioavailability is low. The purpose of this present work is to develop a new microemulsion formulation to improve the stability and bioavailability of MVO. RESULTS: The droplet size, PDI, and zeta potential of Magnolia volatile oil microemulsion (MVOME) were characterized along with its physical characteristics, and these values were found to be 14.270.03 nm, 0.09410.31, and -0.35850.12 mV, respectively, demonstrating the successful formation of microemulsion. In OVA-induced AR rats, MVO-ME dramatically reduced the serum levels of TNF-α, IL-1ß, and IL-6 inflammatory factors. In addition, MVO-ME significantly inhibited the expression of protein levels of PPAR-γ and P65 in the nasal mucosa of AR rats. In this regard, we hypothesized that MVO-ME may play a therapeutic role in AR by activating the PPAR signaling pathway as well as inhibiting the activation of the NF/κB signaling pathway. CONCLUSION: MVO-ME has systematic advantages, such as high solubility, bioavailability, etc. It is expected to be an efficient nano-drug delivery system for the clinical treatment of allergic rhinitis.

Deciphering the antidepressant effects of Rosa damascena essential oil mediated through the serotonergic synapse signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. AIM OF THE STUDY: The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. RESULTS: REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT2A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. CONCLUSIONS: This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil.

Valerian essential oil for treating insomnia via the serotonergic synapse pathway.

Valerian volatile oil can be used in the treatment of insomnia; however, the active components and mechanisms of action are currently unclear. Therefore, we used transcriptome sequencing and weight coefficient network pharmacology to predict the effective components and mechanism of action of valerian volatile oil in an insomnia model induced by intraperitoneal injection of para-Chlorophenylalanine (PCPA) in SD rats. Valerian essential oil was given orally for treatment and the contents of 5-hydroxytryptamine receptor 1 A (5-HT1AR), γ-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in the hippocampus of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA), western blot, Polymerase Chain Reaction (PCR), and immunohistochemistry. The results showed that after treatment with valerian essential oil, insomnia rats showed significantly prolonged sleep duration and alleviated insomnia-induced tension and anxiety. Regarding the mechanism of action, we believe that caryophyllene in valerian essential oil upregulates the 5-HT1AR receptor to improve the activity or affinity of the central transmitter 5-HT, increase the release of 5-HT, couple 5-HT with a G protein coupled receptor, convert adenosine triphosphate (ATP) into cAMP (catalyzed by ADCY5), and then directly regulate the downstream pathway. Following pathway activation, we propose that the core gene protein kinase PKA activates the serotonergic synapse signal pathway to increase the expression of 5-HT and GABA, thus improving insomnia symptoms and alleviating anxiety. This study provides a theoretical basis for the application of valerian volatile oil in health food.

Study of the Mechanism of Antiemetic Effect of Lavandula angustifolia Mill. Essential Oil Based on Ca2+/CaMKII/ERK1/2 Pathway.

Purpose: To investigate the effective components and possible mechanism of action of Lavandula angustifolia Mill. essential oil (LEO) in preventing vomiting through the olfactory pathway. Materials and Methods: A new network pharmacology-based method was established to analyze main components and pathways of LEO involved in antiemetic effects by introducing component content; biological activities of key proteins of the olfactory pathway and their corresponding compounds were verified by molecular docking technique; and finally pica in a rat model was established to verify the molecular mechanism of antiemetic effects of LEO by enzyme-linked immunosorbent assay (ELISA) to determine the serum 5-HT, substance P, and DA levels in each group and by immunohistochemistry to determine the contents of 5-HT3R, CaMKII and ERK1/2 proteins in the medulla oblongata tissue. Results: Network pharmacology combined with molecular docking analysis showed that the mechanism of the antiemetic effect of LEO may be related to (2Z)-3,7-dimethyl-2,6-octadienyl acetate, linalyl acetate, butanoic acid, hexyl ester, 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetate, .tau.-cadinol and other active ingredients, which regulate the cyclic adenosine monophosphate (cAMP) signaling pathway and the expression of BRAF, PDE and other targets on the pathway. An ELISA revealed that LEO reduced the levels of 5-hydroxytryptamine (5-HT), substance P, and dopamine in serum compared with the model group (P <0.05). Immunohistochemical analysis showed that LEO decreased the expression of 5-HT3R, CaMKII, and ERK1/2 proteins in the medulla oblongata of rats compared with the model group (P <0.01). Conclusion: LEO may achieve the antiemetic effect by reducing the content of 5-HT and inhibiting its related receptors, thereby regulating downstream Ca2+/CaMKII/ERK1/2 pathway of the cAMP signaling pathway.

Supersonic gas flow for preparation of ultrafine silicon powders and mechanochemical synthesis.

We report the supersonic gas flow for crush and mechanochemical synthesis. The key instrument parameters for production of supersonic particle flow, such as annular nozzle, expansion angle and length of the accelerating duct, are theoretically designed and optimized. Based on the theoretical results, supersonic gas flow equipment is fabricated. The capacity of the present equipment for production of supersonic particle flow is demonstrated by particle image velocimetry measurement, and the maximum transient velocity of the particles achieves as much as 550 m s-1. Additionally, the present equipment is applied for continuous and physical preparation of ultrafine Si powders with a high scalability and mechanochemical synthesis of TiO2 and TiNx nanopowders at a high production rate.

A supersonic target jet mill based on the entrainment of annular supersonic flow.

Jet mill is an apparatus that produces superfine powder and is widely used in various industries. In this work, a new supersonic target jet mill based on aerodynamic theory is presented according to the flow field of a traditional jet mill. An annular supersonic flow produced by an annular converging-diverging nozzle is used to entrain the central particle flow by the shear mechanism in this new supersonic target jet mill. Then, the particle beam concentrating in the flow center impacts the target with high kinetic energy after the entrainment of the supersonic flow. An apparatus of the annular supersonic target jet mill was created to validate the theoretical design. Two types of experiments were implemented to estimate its performance. The validation experiments confirmed that the gas speed in the collision chamber was approximately 600 m/s and the supersonic flow could deliver a kinetic energy of approximately 180 J/s to the particles. The particle size reduction of boroncarbide (B4C) and silica (Si) in the collision tests showed that the accelerated particles concentrated in the supersonic flow center collided on the targets precisely with high collision energy.

Intravitreal Bevacizumab Injection Attenuates Diabetic Retinopathy in Adult Rats with Experimentally Induced Diabetes in the Early Stage.

Diabetic retinopathy is the leading cause of blindness, yet its treatment is very limited. Anti-VEGF drug has been widely applied in ocular disease, but its effects on diabetic retinopathy and the underlying mechanism have remained to be fully explored. To elucidate the role of anti-VEGF treatment, we sought to determine the effects of bevacizumab on diabetic neurovascular changes extending from the 3rd to 9th week with induced diabetes in adult rats. The retinal neurovascular changes included increased expression of VEGF, nNOS, iNOS, eNOS, and NO in the course of diabetes progression. In diabetic rats given bevacizumab injection, the ganglion cell loss and alterations of retinal thickness were ameliorated. In this connection, the immunofluorescence labeling of the above biomarkers was noticeably decreased. Along with this, Western blotting confirmed that bevacizumab treatment was associated with a decrease of VEGF, Flk-1, and cAMP response element binding and protein kinase C protein expression. The present results suggest that bevacizumab treatment in the early stage of the retinopathy may ameliorate the lesions of retinopathy, in which VEGF/Flk-1 signaling has been shown here to play an important role.

[Study on Pharmacokinetics and Tissue Distribution of Quercetin Submicroemulsion in Mice].

Objective: To study the pharmacokinetic and tissue distribution of quercetin injection and submicron emulsion after intravenous administration in mice. Methods: The concentration of quercetin in mice plasma and tissues were determined by RPHPLC. Results: Liver had the highest tissue concentration of quercetin submicron emulsion, followed by plasma, kidney, spleen, lung, heart and brain. And their had significantly increased compared with the AUC0→tof plasma, liver, spleen, kidney and brain after administration of quercetin injection( P < 0. 05). The Rte and Re of liver, brain and spleen were all larger than 1. Conclusion: Quercetin submicron emulsion significantly alters the plasma pharmacokinetic characteristics of quercetin after intravenous administration in mice. And it has good targeting location features in liver, brain, spleen and kidney.

[Preparation of Curcumin Nanosuspensions and Its Pharmacokinetic Behavior in Rats].

OBJECTIVE: To prepare curcumin nanosuspensions (Cur-NS), and to study the pharmacokinetics of Cur-NS in rats. METHODS: Cur-NS was prepared by the high pressure homogenization technology. The particle size, PdI and Zeta electric potential of nanosuspensions were taken as the indexes to determinate the factors that influenced the preparation process greatly. Curcumin concentrations in plasma were determined by HPLC and the pharmacokinetic parameters were calculated. RESULTS: The particle size, polydisper- sion index, Zeta potential of Cur-NS were found to be 396. 4 ± 67. 2 nm, 0. 369 ± 0. 061 and -16.7 ± 3. 5 mV,respectively. AUC(0-t) of curcumin bulk drugs and Cur-NS were estimated to be 3. 62 ± 0. 66 mg/(L . h) and 14. 36 ± 1. 20 mg/( L . h), half lifes(t1/2) were 0. 62 ± 0. 06 h and 2. 15 ± 0. 15 h tmax were 1. 83 ± 0. 11 h and 1. 02 ± 0. 09 h, Cmax were 0. 94 ± 0.12 mg/L and 5. 78 ± 0. 46 mg/L, respectively. CONCLUSION: The pharmacokinetic results demonstrate that the curcumin bulk drugs prepared into Cur-NS can increase the drug's bioavailability in rats significantly.

[Optimization of Formulation and Process of Paclitaxel PEGylated Liposomes by Box-Behnken Response Surface Methodology].

OBJECTIVE: To develop a procedure for preparing paclitaxel encapsulated PEGylated liposomes. METHODS: The membrane hydration followed extraction method was used to prepare PEGylated liposomes. The process and formulation variables were optimized by "Box-Behnken Design (BBD)" of response surface methodology (RSM) with the amount of Soya phosphotidylcholine (SPC) and PEG2000-DSPE as well as the rate of SPC to drug as independent variables and entrapment efficiency as dependent variables for optimization of formulation variables while temperature, pressure and cycle times as independent variables and particle size and polydispersion index as dependent variables for process variables. The optimized liposomal formulation was characterized for particle size, Zeta potential, morphology and in vitro drug release. RESULTS: For entrapment efficiency, particle size, polydispersion index, Zeta potential, and in vitro drug release of PEGylated liposomes was found to be 80.3%, (97.15 ± 14.9) nm, 0.117 ± 0.019, (-30.3 ± 3.7) mV, and 37.4% in 24 h, respectively. The liposomes were found to be small, unilamellar and spherical with smooth surface as seen in transmission electron microscopy. CONCLUSION: The Box-Behnken response surface methodology facilitates the formulation and optimization of paclitaxel PEGylated liposomes.