Anti-inflammatory & anti-allergy agents in medicinal chemistry最新文献

Background: Obesity is one of the main health problems worldwide and is associated with type 2 diabetes mellitus. In this context, butenolides and sulfonamides are known for their anti-obesity effects.

Objective: The present study aimed to synthesize a novel molecule containing the moieties hydroxybutenolide and sulfonamide [3-chloro-4-(p-chlorophenylsulfonylamino)-5-hy-droxyfuran-2(5H)-one] (FS) and evaluate its metabolic effects in an obese mice model with metabolic syndrome.

Methods: 4 groups of mice were divided into standard diet (ST), standard diet with added hydroxybutenolide (ST+FS), high-fat diet (HF), and high-fat diet with added hydroxy-butenolide (HF+FS). Over 30 days, FS was administered by gavage at a dose of 70 mg/kg/day. Body weight, food consumption, glycemic tests, total serum cholesterol, high-density lipoprotein cholesterol, triacylglycerol, histological analyses, and gene expression by RT-PCR for the adipose tissue genes SIRT1, SIRT3, SIRT5, and NFKβ, were evaluated.

Results: A decrease in body weight was observed after FS administration (ST+FS: -7.81±4.39 and HF+FS: -11.77±9.59), reducing glucose and fasting blood glucose in the treated group. Adipose tissue mass (ST+FS: 0.017 ±0.011; HF+FS: 0.062±0.017), white epididymal adipose tissue volume, triglycerides, as well as the adipocyte area, were lower for the HF+FS group. SIRT1 and SIRT3 expressions were higher in groups that received hydroxybutenolide.

Conclusion: Treatment with FS 3-chloro-4-(p-chlorophenylsulfonylamino)-5-hydroxy-furan-2(5H)-one improved metabolic profile and increased the SIRT1 expression.

Background: Chronic inflammatory diseases are rising, driving the search for effective natural treatments. Mentha pulegium L. and Pimpinella anisum L. (anise) exhibit notable anti-inflammatory properties individually, but their combined effects are less studied. This research evaluates the in vitro synergistic anti-inflammatory activities of their hydroalcoholic extracts. Phytochemical analysis confirmed the presence of flavonoids, tannins, and polyphenols in both extracts. Individually, they demonstrated significant activity (78.5% and 72.3%, respectively, at 10 g/L) compared to Diclofenac (62.3%). Their combination achieved 88.6% inhibition at the same concentration. These findings highlight their potential as natural anti-inflammatory agents.

Introduction: The rise in chronic inflammatory diseases has increased interest in natural anti-inflammatory treatments. Mentha pulegium L. and Pimpinella anisum L. are well-known for their anti-inflammatory potential, attributed to their bioactive compounds like flavonoids and polyphenols. While the individual effects of these plants are established, their combined use is underexplored. This study evaluates the in vitro synergistic anti-inflammatory activity of hydroalcoholic extracts from these plants, aiming to offer an effective natural therapeutic alternative.

Methods: Hydroalcoholic extracts were prepared by maceration of both plants. Anti-in-flammatory activity was assessed using the protein denaturation method with Diclofenac as a standard.

Results: Phytochemical analysis identified flavonoids, alkaloids, tannins, glycosides, and polyphenols in Mentha pulegium, with an absence of saponins. Pimpinella anisum contained flavonoids, tannins, heterosides, and polyphenols. The extracts exhibited strong anti-inflammatory activity individually (78.5% and 72.3%, respectively, at 10 g/L) and even higher inhibition (88.6%) when combined, surpassing Diclofenac (62.3%).

Conclusion: The combination of Mentha pulegium and Pimpinella anisum extracts significantly enhanced anti-inflammatory activity compared to individual extracts, under-scoring their potential as natural therapeutic alternatives to conventional treatments.

The potential of underutilized plant species to improve food security, health, eco-nomic output, and the environment has not been fully realized. Sri Lanka an island on the Indian Ocean is home to numerous plant species with significant medicinal potential, in-cluding many underutilized plants that could help meet the growing demand for food, en-ergy, medicines, and industrial resources. Globally, there are over a thousand known and unknown phytochemicals derived from plants. Although these compounds are primarily produced by plants for self-defence, in vitro and in vivo studies have demonstrated their anti-inflammatory properties. Recent research indicates that several phytochemicals can also protect humans from disease by regulating key inflammatory pathways, such as NF-κB, MAPK, JAK/STAT and Nrf-2, which are involved in autoimmune diseases. Thus, these bioactive compounds are vital for managing autoimmune disorders. This review will ex-plore underutilized fruit crops from Sri Lanka that could be used against inflammation, in-cluding autoimmune diseases.

Background: Indomethacin (IND), classified as class 2 in the Biopharmaceutical Classification System (BCS), has emerged as an anti-inflammatory agent with low solubility and high permeability. Widely used in the treatment of various diseases, such as rheumatoid arthritis and ankylosing spondylitis, this drug is well-known for its adverse effects, particularly in the stomach, and a short biological half-life, which is around 1.5-2 hours.

Objective: The aim of this study was to overcome the challenges of low solubility, short half-life, and serious side effects occurring with the use of IND-loaded formulations of Solid Lipid Nanoparticles (SLNs) and Polymeric Nanoparticles (PNPs).

Methods: For PNPs, emulsification/solvent evoporation method was employed, and for SLNs, the hot homogenizaton method was applied. Eudragit® RLPO (RLPO) and Eudragit® RSPO (RSPO) were used as polymers for PNP and Dynasan®116 (DYN) was used as the solid lipid for SLN. Prepared formulations were characterized for Particle Size (PS), Poly-dispersity Index (PDI), Zeta Potential (ZP), Encapsulation Efficiency (%EE), and drug-ex-recipient compatibility using DSC, FT-IR, and 1H NMR; cumulative drug release rates were assessed using HPLC and in vitro cytotoxicities were examined by the MTT assay.

Results: Both PNP and SLN formulations' zeta potential, particle size, and PDI results indicated the formulations to have good stability. Encapsulation efficiency values were obtained as desired. Drug-excipient compatibility was proved using DSC, FT-IR, and 1H NMR. In vitro dissolution results have proven both formulations to have longer release than pure indomethacin. In the MTT analysis of indomethacin application for 24 and 48 hours, a linear correlation was observed between drug concentration and cell viability, and it was determined that the PNP formulation exhibited fewer toxic effects among the formulations. This has proven the PNP nanocarrier as safer for normal cells.

Conclusion: IND-loaded PNP and SLN formulations have been successfully prepared in this work and they have achieved drug release in the intestine and prolonged the release duration.

Introduction: Eleutherine bulbosa (Miller) Urb, popularly known as "marupa-zinho", is frequently used in traditional medicine for treating various diseases, including hypertension, ulcers, constipation, and intestinal infection. However, there is little scientific knowledge available regarding the pharmacological effects of this species. Thus in vivo and in silico phytochemical studies are required to establish whether this plant has these effects. Further tests were necessary to evaluate the pharmacological activity of the compounds found in this plant, and demonstrate results related to the anti-inflammatory process, which will serve as the basis for future research in this area.

Methods: Therefore, our study aimed to determine the acute toxicity levels of the hexanoic fraction of the ethanolic extract of Eleutherine bulbosa (referred to as ExtHF) using adult zebrafish, with the determination of the LD50, behavioral and histopathological evaluations, as well as the anti-inflammatory potential of ExtHF, at different doses, in abdominal edema induced by carrageenan. The acute toxicity study and histopathological analysis in zebrafish showed that ExtHF has a high toxic potential, with an LD50 of 346.74 mg/kg. However, ExtHF showed an anti-inflammatory effect by inhibiting abdominal edema at all doses tested.

Results: The inhibition rate of 66.2% and 62.4%, respectively, was observed with the 2.5 mg/kg dose, respectively, indicating that ExtHF is safe in terms of acute toxicity based on behavioral changes, mortality rate, and histopathological examination. Therefore, ExtHF has an acceptable level of safety for acute toxicity, defined by the analysis of behavioral changes, mortality, and histopathology, showing a significant anti-inflammatory effect in zebrafish at all doses, showing that ExtHF was very efficient in preventing the formation of edema, in addition, it was also revealed that ExtHF has a great effect in reversing the edema which is already installed.

Conclusion: Molecular docking studies revealed that the eleutherol molecule isolated from E. bulbosa has a dual inhibition profile against cyclooxygenase-1 and 2.

Aims: This study aimed at the synthesis of several spiro[benzofuran-3,3'-pyrroles] derivatives by a three-component reaction conducted by mixing DMAD, N-bridgehead het-erocycles, and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. Moreover, in vitro evaluation of their cytotoxicity affinities against FMS-like tyrosine kinase 3 was carried out.

Objectives: The objective of this study was to use a one-pot, three-component reaction to synthesize a novel set of spiro[benzofuran-3,3'-pyrroles] derivatives.

Methods: A novel set of spiro[benzofuran-3,3'-pyrroles] ((11-13)a-e) was synthesized by a one-pot three-component reaction involving dimethyl acetylenedicarboxylate, N-bridgehead heterocycles and benzofuran-2,3-diones in dichloromethane at room temperature for 24 h. The compounds were analyzed using NMR 1H, 13C, 2D-NMR (COSY, HMQC, HMBC), and HRMS. Docking simulations were conducted to elucidate the anticancer activity of synthe-sized compounds on FLT3 protein, with Gilteritinib as a reference for comparison.

Results: This study demonstrated the successful design, synthesis, and biological evaluation of spiro[benzofuran-3,3'-pyrroles] derivatives as FLT3 inhibitors for AML treatment. The synthesized compounds demonstrated promising binding affinities and significant inhibitory activity against FLT3 kinase. The inhibitors (11a, 11b, 11c, 12d, and 12e) exhibited excellent selectivity profiles against FLT3. Particularly, compound 12e showed strong binding affinity and potent inhibitory activity (IC50 = 2.5 μM).

Conclusion: Fifteen new synthetic spiro[benzofuran-3,3'-pyrroles] were prepared, character-ized, and evaluated for cytotoxicity affinities against FMS-like tyrosine kinase 3. Compound 12e showed strong binding affinity and potent inhibitory activity (IC50 = 2.5 μM), making it a promising candidate for further development as a therapeutic option for AML treatment. These findings lay the groundwork for further optimization and development of spiro[benzo-furan-3,3'-pyrroles] derivatives as potential therapeutics for AML treatment. Further studies are needed to explore their efficacy and safety profiles in preclinical and clinical settings.

Objective: This study assessed the In-vitro Antioxidant and In-vivo Analgesics and Anti-inflammatory Activity of Allamanda blanchetii Leaf Extract in Rats.

Introduction: Diverse pharmacological applications of plants from the Apocynaceae family are reported in the literature. Allamanda blanchetii; an ornamental species belonging to the Apocynaceae family, is characterized by diverse biological activities, i.e. antioxidant, cyto-toxic, thrombolytic, membrane-stabilizing, antimicrobial, and anti-proliferative effects. This species represents a perennial flora that thrives in tropical and subtropical climates.

Material and methods: Ultrasonication-assisted method used for plant extraction. The ex-tracts were subjected to phytochemical screening tests, followed by total phenolic content analysis, using gallic acid as a standard. The antioxidant activity was examined by DPPH scavenging and FRAP assays. The acetic acid-induced writhing test, tail flick, and Hot plate method were used for the determination of analgesic activity. Anti-inflammatory activity by following carrageenan-induced paw edema Results: ABLE treatments show analgesic effectiveness against the acid-induced pain source, tail flick, and hot plate methods at different doses of ABLE 400,200,100 mg/kg results showed respectively- 55.32, 38.67, and 22.85 (% inhibition), 89.47%, 62.57 %, 49.57%, and 100%, 92.40%, 65.33% response after 180 min of drug administration. ABLE 400 and 200 mg/kg exhibit effective results (1.43± 0.005 and 1.50± 0.008) against carra-geenan-induced intoxication.

Discussion: The fundamental components of antioxidants that can aid in the reduction of free radicals include phenol, flavonoids, and polyphenols. Applying DPPH and FRAP, ABLE exhibits remarkable antioxidant activity. When it comes to both centrally and periph-erally acting analgesics, ABLE exhibits highly effective activity. Methanolic ABLE had a noticeable impact on paw edema caused by carrageenan. Antioxidants, alkaloids, and gly-cosides were present in methanolic ABLE, which allowed it to efficiently combat inflam-matory mediators and the cause of pain.

Conclusion: Ultrasonic assistance is beneficial in isolating active metabolites in plants, with phenolic compounds exhibiting antioxidant activity. ABLE, a plant with 55% squalene, ef-fectively combats inflammatory mediators and pain. Further investigation is needed to iden-tify biomarkers in the plant.

Plant-based repellents have been used for generations as personal protection against mosquitoes. Ethnobotanical studies provide valuable knowledge for developing natural prod-ucts. Commercial repellents with plant-based ingredients are popular, but insufficient studies follow Pesticide Evaluation Scheme WHO guidelines. Further standardized studies are needed to evaluate repellent compounds and develop high-repellency and safe products. Essential Oils (EOs) from aromatic plants have gained popularity as low-risk insecticides due to their low toxicity and short environmental persistence. These plant-derived EOs, produced through steam distillation, have repellent, insecticidal, and growth-reducing effects on various insects. They control phytophagous insects, bite flies, and home and garden insects. US registration is the main hurdle for new EOs. This review explores the use of essential oils from plants as a natural repellent, focusing on their effectiveness and synergistic effects. Essential oils are vol-atile mixtures of hydrocarbons with diverse functional groups, and their effectiveness is linked to monoterpenes and sesquiterpenes. Synergistic effects can improve their effectiveness, and the use of other natural products, like vanillin, can increase protection time. Cymbopogon spp., Ocimum spp., and Eucalyptus spp. are among the most promising plant families.

In today's time, a diversity of neurodegenerative diseases that widely affect the CNS causing insufficiency in particular brain processes such as memory, mobility, and cognition due to the moderate loss of CNS neurons. This review emphasizes different phytochemical constituents used widely for the prevention or treatment of various neurodegenerative diseases such as Alzheimer's disease (AD) and Parkin-son's disease (PD). Berberin (BBR), which is an isoquinoline class of alkaloid and isolated from the plant Hydrastis condenses and Berberis aaristata, has both acetylcholine esterase (AChE) inhibiting properties as well as monoamine oxidase (MAO) inhibiting properties involved in the betterment of AD by decreasing the production of reactive oxygen species (ROS). Like BBR, Physostigmine, isolated from the Physostigma venenosum / Calabar bean and belongs to the family Leguminosae, and Morphine, isolated from the plant Papaver somniferum / Opium poppy or Breadseed poppy, also has a significant impact on the management and treatment of AD and PD by reducing both neuroinflammation and pro-inflammatory cytokines production. Morphine bineurodegenerative diseases with μ-opioid receptor (MOR) in CNS elevate GABA levels in the synaptic cleft of the brain and reduces the neurotoxicity via stimulation of MOR. It has been discovered that physostigmine improves cognitive function in AD patients and reduces α-synu-clein expression in PD neural cell lines. Isorhyncophylline (IRN) is a Chinese herbal medicine isolated from the plant Uncaria rhyncophylla which provides neuroprotective efficiency against neurotoxicity that occurs by amyloid β (the main component of amyloid plaques) found in the brain of people with AD.