Pharmacological Applications Research Articles

Anti Urolithiatic and Diuretic Potentiality of Hemidesmus indicus R. Br.

Aim: The present study investigated the development of kidney stone formation in animal models involving renal tubular stone formation by ethylene glycol and COX-2 selective inhibitor-induced urolithiasis along with the diuretic potentiality by Lipschitz teston Wistar rats. Background: Hemidesmus indicus (H. indicus) R. Br. played a prominent role in various ancient traditional systems of medications and possessed various pharmacological applications. Since the last few decades, urolithiasis has been a major constraint in both livestock and human health. Celecoxib administration increased urinary enzyme excretion but did not affect oxalate or citrate excretion in a urolithiasis model. Objective: This research provides a comprehensive account of the ethnobotanical use of H. indicus as an antiurolithiatic and diuretic agent in animal models. Methods: The plant material was dried, pulverized into a dry powder, extracted with ethanol, and analyzed for the presence of various secondary metabolites. The anti-urolithic effect of ethanolic extract of H. indicus roots in albino rats was investigated using ethylene glycol (0.75%) and COX -2 selective inhibitor models Results: The experimental data showed the significant effect of H. Indicus root extract (HIEE) as anti-urolithiasis by the prevention of kidney stone formation, also by decreasing crystal nucleation, growth inhibition, decreased aggregation, and crystal retention within the renal tubules. The effect of HIEE supplementation prevents the impairment of renal stone formation, which was also confirmed by the histological findings. HIEE also acts as a potent diuretic, which supports the study. Conclusion: The results indicated that HIEE was effective against experimentally induced urolithiasis, and it also acts as a potent diuretic in treated animals. So, it needs to perform future research on medicinal plants, including in vivo mechanistic and human studies for urolithiasis.

Solvent-Free Synthesis of Bioactive Heterocycles

: The main emphasis of green chemistry is to reduce environmental pollution. Its main goal is to adopt a cost-effective and harmless strategy for human health and the environment. The green synthetic routes have succeeded in adopting solvent-free conditions as an effective tool for sustainability. Heterocycles are organic compounds that are widely distributed by nature. Many of them possess medicinal and pharmacological properties, as this heterocyclic moiety is found in many drugs. The solvent-free strategies for the Synthesis of bioactive heterocycles are, now-adays, regarded as an important objective. Solvent-free reactions are eco-friendly, cost-effective, and an environmentally benign route in organic transformation methods because of their effi-ciency, reduced reaction time, and high yields, thereby saving energy. This mini-review focuses on the environmentally benign solvent-free Synthesis of heterocycles and their potential pharma-cological applications.

Croton cajucara: Patents and Nanotechnological Advances.

Croton cajucara Benth showed several pharmacological properties such as: antiinflammatory, antinociceptive hypoglycemic, lipid-lowering, antiulcer, antiestrogenic, antitumor, antigenotoxic, antimutagenic, and cardiovascular. The 19-nor-clerodane diterpene transdehydrocrotonin (t-DCTN or DCTN) is the major bioactive constituent extracted from the bark of this Croton. Patents for Croton cajucara Benth in the period 2015 to 2022 comprises 14 published documents. Among them 4 patents are colloidal systems (SM/SNEDDS) loading t-DCTN for pharmacological applications. Patent registrations highlighted the huge promising biotechnological potential of Croton cajucara Benth especially in the phytotherapy field, and the correlation with its bioactive constituents of which t-DCTN showed the foremost results, so this herbal could become an alternative in the treatment of COVID-19. However, investigation of more recently published patents for clerodane diterpenes with similar chemical structure of t-DCTN, who previously showed antiviral property must be carried out and should be searched on several patent data bases.

Revealing the Bioactivities of Physalia physalis Venom Using Drosophila as a Model

Physalia physalis, commonly known as the Portuguese Man o’ War, is one of the most venomous members of the Cnidaria yet is poorly understood. This article investigates the toxicity of P. physalis venom by assessing its behavioral and toxicological effects on Drosophila melanogaster. The venom administered orally revealed dose- and time-dependent mortality, with an LD50 of 67.4 μg per fly. At sublethal doses, the treated flies displayed uncoordinated movement and fell when attempting to climb. Real-time analysis of flies exposed to the venom revealed hyperexcitability followed by paralysis, with phenotypes similar to those observed in vertebrate models. The venom was shown to be non-thermolabile, as no significant differences in behavior and locomotion were observed between flies exposed to untreated or thermally treated venom. The circadian rhythm alterations, the enhanced light attraction, and the reduction in heat avoidance suggest altered neuronal function. This abnormal behavior indicates that the venom contains bioactive molecules, opening avenues for discovering new compounds with potential for pharmacological applications.

Synthesis and preliminary cytotoxicity evaluation of water soluble pentacyclic triterpenoid phosphonates.

Synthesis, solubility and cytotoxicity evaluation of anionic phosphonates derived from betulin, betulinic acid, oleanolic acid and ursolic acid is reported. Phosphonate moieties were successfully installed at terpenoid C28 by carboxylic acid deprotonation/alkylation sequence using (dimethoxyphosphoryl)methyl trifluoromethanesulfonate as alkylation reagent. Also, betulin-derived and ether-linked bis-phosphonate is obtained and characterized. After demethylation in the presence of TMSI the resulting phosphonic acids were transformed into their disodium salts. All target compounds display excellent water solubility, which was determined by qNMR in D2O. Cytotoxicity tests were performed in different concentrations of each compound (10-50 µM) against human osteosarcoma cell line MG-63 and osteoblast precursor cell line MC3T3-E1. Improved aqueous solubility and low cytotoxicity profile of the newly designed triterpenoid phosphonates reveal high potential for various medicinal chemistry and pharmacological applications in the future.

Introduction to Instruments used in Pharmacology with its Application

Pharmacology is a multidisciplinary field that focuses on the study of drug interactions, mechanisms of action, and therapeutic effects. The advancement of pharmacological research and clinical applications is heavily dependent on various specialized instruments that enable precise measurement, analysis, and monitoring of drug properties and their effects on biological systems. Instruments used in pharmacology range from simple laboratory tools, such as spectrophotometers and chromatographs, to more complex systems like high chromatography (HPLC), mass spectrometry (MS), and in vivo imaging devices. These tools are essential for drug discovery, pharmacokinetic studies, dose assessments, and toxicological evaluations. The development and application of these instruments allow researchers to accurately quantify drug concentrations, monitor physiological changes, and identify potential drug targets, thereby facilitating the discovery of safe and effective pharmaceutical agents. This introduction provides an overview of the fundamental instruments commonly used in pharmacology and highlights their critical roles in modern drug development and research..

Multicomponent Cyanation of 2‐Amino‐3‐cyano‐4H‐chromenes in Aqueous Media

AbstractChromenes represent a pivotal molecular structure found in a diverse range of biologically active compounds. Specifically, derivatives of 2‐amino‐3‐cyano‐4H‐chromene have demonstrated pharmacological applications, displaying potential antioxidant and anticancer activities. This has heightened interest in the exploration of new and more efficient methods for their synthesis. In recent years, few examples have emerged, focusing on the organocatalytic and enantioselective synthesis of 2‐amino‐3‐cyano‐4H‐chromene derivatives, although the overall number of works to date is limited. In this study, we present the results of the synthesis of 2‐amino‐4H‐chromen‐3,4‐dicarbonitriles through a Michael addition of cyanide to 2‐iminochromenes. To achieve this, we utilized a mild source of cyanide (acetone cyanohydrin), green solvents and catalytic conditions at room temperature, via a multicomponent approach. Furthermore, we initiated the enantioselective study of this process using chiral organocatalysts obtaining promising preliminary results.

Anti-Inflammatory and Antioxidant Activities of Eugenol: An Update

Medicinal plants are a rich source of bioactive compounds that possess pharmacological properties for preventing and treating inflammation-related diseases. Essential oils is a chemical class that contains many bioactive compounds, such as eugenol, which is capable of inhibiting or modulating the inflammatory response. This natural product emerges as a compound that promotes various biological activities, including antioxidant activity, which makes it useful in the food industry. Recently, its pharmacological applications have also been highlighted. So, this review aims to update and discuss the most recent findings on the anti-inflammatory and antioxidant activities of eugenol, along with its mechanisms of action and therapeutic potential for treating inflammation and oxidative imbalance conditions.

MTS, WST-8, and ATP viability assays in 2D and 3D cultures: Comparison of methodologically different assays in primary human chondrocytes.

Tissue engineering enables the production of three-dimensional microtissues which mimic naturally occurring conditions in special tissues. These 3D culture systems are particularly suitable for application in regenerative medicine or experimental pharmacology and toxicology. Therefore, it is important to analyse the cells in their 3D microenvironment with regard to viability and differentiation. Tetrazolium assays (WST-8 and MTS) are still the methods of choice for estimating the number of living, metabolically active cells, with WST-8 being cell-impermeable compared to MTS. In contrast to these methods, the ATP assay is an endpoint method based on the luciferase-induced reaction of ATP with luciferin after cell lysis. We compared three methodologically different proliferation/toxicity assays (MTS, WST-8, ATP) in monolayer (2D) and 3D culture systems to improve the technically challenging determination of the number of viable cells. Chondrocytes were isolated from human articular cartilage. Three different test systems (MTS, WST-8, ATP) were applied to monolayer cells (2D, varying cell numbers) and spheroids (3D, different sizes) in 96-well plates. The intracellular ATP concentration was determined by luciferase-induced reaction of ATP with luciferin using a luminometer. Formazan formation was measured spectrophotometrically after different incubation periods. Evaluation was performed by phase contrast microscopy (toxicity), correlation of cell count and ATP concentration or absorption signal (Gompertz function) and propidium iodide (PI) staining to proof the cell lysis of all cells in spheroids. In 2D culture, all three assays showed a good correlation between the number of seeded cells and the ATP concentration or absorption data, whereas the MTS-assay showed the lowest specificity. In 3D culture, the spheroid sizes were directly related to the number of cells seeded. The absorption data of the WST-8 and MTS assay correlated only for certain spheroid size ranges, whereas the MTS-assay showed again the lowest specificity. Only the measured intracellular ATP content showed a linear correlation with all spheroid sizes ranging from 100-1000 μm. The WST-8 assay revealed the second-best sensitivity which allows the measurement of spheroids larger than 240 μm. Phase contrast observation of monolayer cells showed toxic effects of MTS after 6 h incubation and no signs of toxicity of WST-8. Staining with propidium iodide showed complete lysis of all cells in a spheroid in the ATP assay. Among tetrazolium-based assays, WST-8 is preferable to MTS because of its non-toxicity and better sensitivity. When determining the number of viable cells in the 2D system, caution is advised when using the ATP assay because of its two-phase slope of the correlation graph concerning cell number and intracellular ATP. In 3D systems of human chondrocytes, the ATP-assay is superior to the other two test systems, as the correlation graph between cell number and intracellular ATP is biphasic. Since differentiation processes or other metabolic events can influence the results of proliferation and toxicity assays (determination of viable cells), this should be taken into account when using these test systems.

The Chemistry and Pharmacological Properties of the Constituents of Toussaintia Orientalis - An Endangered Treasure of Biomedical Agents.

Toussaintia orientalis Verdc. (Annonaceae) is a medicinal plant species endemic to Tanzania. It is classified under the International Union for Conservation of Nature (IUCN) as an extremely endangered species threatened with extinction. The review covers the phytochemistry of this plant species and the pharmacological properties of the compounds obtained therefrom. The chemistry of this plant species entails natural products with different structures including uncommon cinnamoyl tetraketide derivatives, aristolactam alkaloids, and flavonoids. The review identifies 27 compounds belonging to different subclasses of natural products obtained from this species for the past fourteen years (2010-2024). These compounds are discussed along with other 13 related natural products. T. orientalis derived compounds exhibit varied potential pharmacological applications as antibacterial, anticancer, anti-inflammatory, antiviral, and neuroprotective agents. Some of the reported compounds displayed pharmacological properties corroborating the use of this plant species in traditional medicine. This review provides baseline data as one comprehensive compilation that will ignite interest and guide future research and development of therapeutic agents inspired by the chemodiversity presented by this plant species while at the same time attracting the attention of plant conservationists to initiate efforts to conserve this highly endangered biomedical treasure.

Synthesis, Crystal Structure, Spectroscopic Characterization, In Vitro and In Silico Molecular Docking Studies of Benzyl Tetrazole-N-Isobutyl Acetamide Hybrid

Background: Tetrazole-based compounds are of significant interest due to their potential pharmacological applications. The current study focuses on the synthesis and analysis of such a compound. Objective: This research aims to synthesize the title compound N-(3-methyl-1-phenyl-2-(1Htetrazol- 1-yl) butyl) acetamide, analyze its crystal structure, perform computational studies, and evaluate its potential pharmacological activities and it’s in silico and in vitro supports, specifically antidiabetic and anti-inflammatory properties. Methods: The title compound, C14H19N5O, was synthesized, and its crystal structure was confirmed using single-crystal X-ray diffraction analysis by default parameters. Density Functional Theory (DFT) calculations were performed using the Gaussian 09W software package with the B3LYP/6-311++G (d,p) method to optimize the compound's structure and calculate its HOMOLUMO energy gap, Molecular Electrostatic Potential (MEP), and Mulliken charge distribution. In vitro, antidiabetic and anti-inflammatory activities were assessed and compared with standard drugs by using reported protocols. Additionally, molecular docking studies were conducted with enzymes related to diabetes and inflammation with default parameters, and Auto-Dock 4.2 software was used. Results: The X-ray diffraction analysis confirmed the crystal structure, and the Density Functional Theory (DFT) calculations provided insights into the molecular properties of the compound. Molecular docking experiments with relevant enzymes further supported the significant antidiabetic and anti-inflammatory activities demonstrated in the in vitro tests. Conclusion: The synthesized tetrazole-based compound exhibits promising antidiabetic and antiinflammatory activities, supported by both experimental and theoretical studies, suggesting its potential for further pharmacological investigation.

Phytochemical Diversity and Biological Effects of Juniperus Thurifera L., Essential Oil : A Comparative Study using In Vitro and In Silico Methods.

Juniperus thurifera L., a plant endemic to the Moroccan High Atlas Mountains, thrives in extreme climatic conditions, resulting in the production of valuable secondary metabolites. This study aims to elucidate the phytochemical diversity and biological activities of J. thurifera essential oil (JTEO) through a comparative analysis of samples from two distinct regions: Tensift-Al Haouz and Azilal, using both in vitro and in silico methods. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed 21 components in the Tensift-Al Haouz JTEO (99.99 % of the oil) and 23 components in the Azilal JTEO (99.58 % of the oil), with oxygenated monoterpenes being the predominant compounds in both. The biological activities were assessed in vitro. Antioxidant properties, evaluated using DPPH, FRAP, and ABTS assays, showed significant activity in both oils. Antibacterial activity was tested against two strains of Gram-positive and two strains of Gram-negative bacteria, with both oils demonstrating notable bacterial growth inhibition. Enzymatic assays assessed the antidiabetic (α-amylase and α-glucosidase), dermo-protective (tyrosinase and elastase), and neuroprotective (AChE and BChE) activities. Both oils displayed substantial inhibitory effects across all tested activities, with variations attributed to their distinct chemical compositions. In silico analyses of six target enzymes confirmed significant binding affinities of the major compounds. Notably, 2,2'-Thiobis(6-tert-butyl-p-cresol) exhibited strong binding affinities with AChE, BChE, α-amylase, α-glucosidase, tyrosinase, and elastase, with binding energies ranging from -10.0 to -6.2 kcal/mol. These findings indicate that JTEO is a rich source of bioactive compounds with promising potential in pharmacological and cosmetic applications.

Study on the Mechanism of Raspberry (Rubi fructus)in Treating Type 2 Diabetes Based on UPLC-Q-Exactive Orbitrap MS, Network Pharmacology, and Experimental Validation.

The aim of this study is to analyze the chemical composition of raspberry using liquid chromatography-mass spectrometry (LC-MS) technology, predict the potential effects of raspberry in treating type 2 diabetes through network pharmacology, and conduct preliminary validation through invitro experiments. A Waters CORTECS C18 column (3.0 mm × 100 mm, 2.7 μm) was used; mobile phase A consisted of 0.1% formic acid in water and mobile phase B consisted of 0.1% formic acid in acetonitrile. Gradient elution was performed with full-scan mode in both positive and negative ion modes, covering a mass range of m/z 100-1500. The chemical components of raspberry were analyzed and identified based on secondary spectra from databases and relevant literature. The disease targets related to type 2 diabetes were searched, and protein-protein interaction network analysis as well as gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted on the intersecting targets of the active components of raspberry and the disease. HepG2 cells were used for experimental validation, with high glucose-induced insulin resistance models established. The CCK-8 method was employed to assess the effects of raspberry on cell proliferation, while Western blotting was used to measure the expression of proteins related to the AGE/RAGE signaling pathway. A total of 47 components were identified, including 10 organic acids, 15 flavonoids, 12 phenols, 2 alkaloids, 4 terpenoids, 1 miscellaneous compound, 1 stilbene, 1 steroid and its derivatives, and 1 diterpenoid. Through database screening, seven active components were identified: kaempferol, epicatechin, ellagic acid, crocetin, stigmasterol, fisetin, and isorhamnetin. KEGG and GO results indicated that the therapeutic effects of raspberry on type 2 diabetes may be related to the advanced glycation end product (AGE)- receptor for advanced glycation end product (RAGE) signaling pathway. Establishment of an insulin resistance model in HepG2 cells demonstrated that, compared to the control group, the raspberry treatment group upregulated p53 protein expression while downregulating the expression of RAGE, Akt1, and Caspase-3 proteins. This study preliminarily elucidates that the therapeutic effects of raspberry in treating type 2 diabetes may be mediated through the inhibition of the AGE-RAGE signaling pathway, providing important references for the study of the pharmacological basis and clinical application of raspberry.

Next steps for targeted protein degradation.

Targeted protein degradation (TPD) has greatly advanced as a therapeutic strategy in the past two decades, and we are on the cusp of rationally designed protein degraders reaching clinical approval. Offering pharmacological advantages relative to occupancy-driven protein inhibition, chemical methods for regulating biomolecular proximity have provided opportunities to tackle disease-related targets that were undruggable. Despite the pre-clinical success of designed degraders and existence of clinical therapies that serendipitously utilize TPD, expansion of the TPD toolbox is necessary to identify and characterize the next generation of molecular degraders. Here we highlight three areas for continued growth in the field that should be prioritized: expansion of TPD platform with greater spatiotemporal precision, increased throughput of degrader synthesis, and optimization of cooperativity in chemically induced protein complexes. The future is bright for TPD in medicine, and we expect that innovative approaches will increase therapeutic applications of proximity-induced pharmacology.

Quinoline-hydrazone Conjugates: Recent Insights into Synthetic Strategies, Structure-activity Relationship, and Biological Activities

: The fusion of two distinct and free pharmacologically active chemical moieties into single conjugate molecules can result in synergized pharmacological action of both moieties into the new composite molecule. Ultimately, it increases the therapeutic potentialof the newly formed hybrid compound which is more than the combination of each specific moiety’s therapeutic potential. So nowadays, it is common practice to combine at least two pharmacophores to create a particular compound with a powerful therapeutic effects. Quinoline has been reported with multiple pharmacological activities and industrial applications. On the other hand, hydrazones are also found very useful as herbicides, acaricides, rodenticides, insecticides, and various therapeutic applications. The conjugate containing quinoline and hydrazone is also being used as an anticancer, antibacterial, antifungal, antimalarial, anticonvulsant, anti-inflammatory, and antioxidant. The combination of two moieties yields a better therapeutic effect because of excellent efficacy and fewer side effects. Several synthetic methods have been employed in recent times to synthesize quinoline-hydrazone conjugates which are listed in the manuscript with their merits and demerits. The structure-activity relationship relating to their pharmacological actions with molecular structure has also been highlighted. The article aims to provide a good toolkit and comprehension to the medicinal chemists, for their future work, comprising of quinoline-hydrazone hybrid compounds.

The antisickling agent, 5-hydroxymethyl-2-furfural: Other potential pharmacological applications.

For the last two decades, the aromatic aldehyde 5-hydroxymethyl-furfural (5-HMF) has been the subject of several investigations for its pharmacologic potential. In 2004, the Safo group reported that 5-HMF has potent antisickling activity by targeting and ameliorating the primary pathophysiology of hypoxia-induced sickling of erythrocytes (red blood cells [RBC]). Following the encouraging outcome of the preclinical and phase I/II clinical studies of 5-HMF for the treatment of sickle cell disease (SCD), there have been multiple studies suggesting 5-HMF has several other biological or pharmacologic activities, including anti-allergic, antioxidant, anti-hypoxic, anti-ischemic, cognitive improvement, anti-tyrosinase, anti-proliferation, cytoprotective, and anti-inflammatory activities. The wide range of its effects makes 5-HMF a potential candidate for treating a variety of diseases including cognitive disorders, gout, allergic disorders, anemia, hypoxia, cancers, ischemia, hemorrhagic shock, liver fibrosis, and oxidative injury. Several of these therapeutic claims are currently under investigation and, while promising, vary in terms of the strength of their evidence. This review presents the research regarding the therapeutic potential of 5-HMF in addition to its sources, physicochemical properties, safety, absorption, distribution, metabolism, and excretion (ADME) profiles.

Microwave‐Assisted One‐Pot Synthesis of Tetrahydro‐β‐Carbolines by Fe(II)‐Catalyst: Utilizing Methanol as Methylene Synthon

AbstractThe synthesis of tetrahydro‐β‐carbolines (THβCs) framework is a fundamental aspect of medicinal chemistry due to their significant pharmacological applications. Herein, we developed a microwave‐assisted novel approach for the synthesis of THβC scaffolds utilizing ferrous(II) chloride as an earth abundant metal catalyst and methanol used as valuable methylene source. This methodology demonstrates excellent functional group tolerance and provides N2‐substituted THβCs in good to excellent yields. Overall, this study highlights a sustainable and practical strategy for the synthesis of biologically important THβCs, thereby offering promising prospects in the drug discovery and development.

Vibrational, theoretical characterisation and In Silico investigation of Norcinnamolaurine: a natural lead for inhibiting AURKA and overcoming immune evasion in Triple-Negative Breast Cancer

ABSTRACT Alkaloids represent a diverse category of natural compounds with noteworthy pharmacological and therapeutic applications. Benzylisoquinoline alkaloids (BIAs) are distinguished by their varied structures and potential medicinal properties. This study specifically investigates Norcinnamolaurine, a BIA found in multiple species and acknowledged for its therapeutic advantages. In the current investigation, we comprehensively analyzed Norcinnamolaurine, encompassing Frontier Molecular Orbital studies, vibrational spectroscopy, nonlinear optical properties, natural bond orbital evaluations, and Fukui's analysis. Additionally, we executed an E-pharmacophore-based screening utilizing the AURKA-Norcinnamolaurine complex. The generated hypothesis underwent database screening; lead compounds from the Natural Product and Drug Bank databases exhibited enhanced binding affinities ranging from −8.602 to −7.148 kcal/mol, demonstrating improved interactions within the AURKA binding pocket. Subsequently, the identified lead compounds were subjected to further analysis via MMGBSA, DFT, and Molecular Dynamics Simulations (MDS). Our findings indicate that Norcinnamolaurine exhibits a superior binding affinity towards the target protein. Significant outcomes were also observed in the vibrational and FMO studies. Moreover, MDS analysis revealed that the resultant complexes maintained relative stability, exhibiting minimal deviation and fluctuations. This stability was corroborated through additional assessments using MMPBSA and PCA/FEL methodologies.

Total Synthesis Analysis of Pseuboyenes D

In this work, we propose a total synthesis route for the antifungal agent Pseuboyenes D, a compound derived from Pseudallescheria boydii CS-793. Pseuboyenes D exhibits antifungal activity comparable to Amphotericin B while offering the advantage of a simpler structure, making it a promising candidate for clinical applications. The system became the focus of this analysis due to its regioselectivity, and after exploration, a [2+2] photocycloaddition and ring expansion strategy was adopted to construct the key bridged ring system. The route employs readily available substrates and mild reaction conditions, making it scalable and suitable for large-scale production. Computational analysis of the regioselectivity of the photocycloaddition revealed that the bridged adduct was thermodynamically favored over the fused system. The synthetic route was further diversified by incorporating functional group modifications using TMS derivatives, enhancing the potential for pharmacological applications. Overall, this work establishes an efficient and scalable synthetic pathway for Pseuboyenes D, paving the way for future applications in antifungal drug development.

Alpha-Pinene-encapsulated lipid nanoparticles diminished inflammatory responses in THP-1 cells and imiquimod-induced psoriasis-like skin injury and splenomegaly in mice.

Psoriasis, a persistent skin condition caused by the disorder of the immune system, impacts approximately 1.25 million individuals globally. Nevertheless, the presence of adverse effects in conventional clinical drugs necessitates further exploration of novel medications or combination therapies to mitigate these reactions and enhance their effectiveness. Hence, our intention here in this paper is to utilize the lipid nanoparticle delivery system for overcoming the volatility and hydrophobic properties of α-pinene, a naturally occurring compound renowned for its anti-inflammatory and antiviral effects, and further explore its potential pharmacological applications both in vitro and in vivo. The production of α-pinene lipid nanoparticles (APLNs) was achieved through the utilization of high pressure homogenization methods. APLNs was successfully fabricated with enhanced stability and water solubility. Meanwhile, the application of APLNs could drastically reduce the expression of lipopolysaccharide (LPS)-induced inflammation-related factors in THP-1 cells. Administration of APLNs to a mouse model of auricular swelling could effectively reduce redness and swelling in the auricles of mice as well. Furthermore, APLNs were also found to alleviate skin damage in mice with Imiquimod (IMQ)-induced psoriasis model, as well as decrease the levels of psoriasis-related protein nuclear factor kappa-B (NF-κB) and interleukin-17 (IL-17), interleukin-23 (IL-23), and other inflammation-related cytokines. More importantly, utilization of APLNs successfully mitigated the systemic inflammatory reactions in mice, resulting in the reduction of spleen-to-body ratio (wt%) and of inflammatory cytokines' expression in the serum. Overall, our results suggest that with the help of lipid nanoparticle encapsulation, APLNs possess a better pharmacological effect in anti-inflammation and could potentially serve as an anti-psoriasis drug.