Small molecules in the treatment of COVID-19

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 5, 2022

Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies economies. Until now, effective therapeutics against are in high demand. Along with our improved understanding the structure, function, pathogenic process SARS-CoV-2, many small molecules potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition viral proteins such as RdRp M pro , interference host enzymes including ACE2 proteases, blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, NLRP3 pathways, regarded feasible drug development. development treat achieved strategies, computer-aided lead compound design screening, natural product discovery, repurposing, combination therapy. Several representative remdesivir paxlovid proved or authorized emergency use countries. And candidates entered clinical-trial stage. Nevertheless, due epidemiological features variability issues it is necessary continue exploring novel COVID-19. This review discusses current findings for treatment. Moreover, their detailed mechanism action, chemical structures, preclinical clinical efficacies discussed.

Language: Английский

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Pharmacological activities of esculin and esculetin: A review

Medicine, Journal Year: 2023, Volume and Issue: 102(40), P. e35306 - e35306

Published: Oct. 6, 2023

Esculin and esculetin are 2 widely studied coumarin components of Cortex Fraxini , which is a well-known herbal medicine with 2000-year history. In vivo in vitro studies have demonstrated that both variety pharmacological activities, including antioxidant, anti-tumor, anti-inflammatory, antibacterial, antidiabetic, immunomodulatory, anti-atherosclerotic, so on. Their underlying mechanisms action biological activities include scavenging free radicals, modulating the nuclear factor erythroid 2-related pathway, regulating cell cycle, inhibiting tumor proliferation migration, promoting mitochondrial pathway apoptosis, NF-κB MAPK signaling pathways, CD4 + T cells differentiation associated cytokine release, vascular smooth muscle cells, etc. This review aims to provide comprehensive information on esculin esculetin, noteworthy importance exploring therapeutic potential compounds.

Language: Английский

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Cinnamomum verum extract inhibits NOX2/ROS and PKCδ/JNK/AP-1/NF-κB pathway-mediated inflammatory response in PMA-stimulated THP-1 monocytes

Phytomedicine, Journal Year: 2023, Volume and Issue: 112, P. 154685 - 154685

Published: Jan. 30, 2023

Cinnamomum verum J. Presl (Cinnamon) is widely used in the food and pharmaceutical industries. C. exhibits various biological activities. However, it unclear whether can inhibit NOX, a major source of ROS generation, exert anti-inflammatory antioxidant effects PMA-stimulated THP-1 cells.This study investigates cells.The MeOH extract was analyzed using UPLC-QTOF/MS. Anti-inflammatory were examined by DCF-DA staining, immunofluorescence RT-PCR, immunoblotting cells.C. its components, cinnamic acid coumarin, significantly attenuated expression IL-1β, IL-8, CCL5, COX-2 THP-1. decreased levels via NOX2 downregulation, as well ameliorated plasma membrane translocation PKCδ JNK phosphorylation. Besides, suppressed nuclear AP-1 NF-κB, which modulates diverse pro-inflammatory genes.C. effectively inhibits inflammation oxidative stress during monocyte-macrophage differentiation downregulates inflammatory mediators NOX2/ROS PKCδ/JNK/AP-1/NF-κB signaling.

Language: Английский

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Essential oil from Cinnamomum cassia Presl bark regulates macrophage polarization and ameliorates lipopolysaccharide-induced acute lung injury through TLR4/MyD88/NF-κB pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155651 - 155651

Published: April 17, 2024

Language: Английский

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Phytochemical investigation and assessment of the anti-inflammatory activity of four Heracleum taxa growing in Turkey

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Heracleum L. has been known as "hogweed" and used for inflammatory diseases, including fever, enteritis, bronchitis, many years worldwide. The genus is also prominently recognized its high content of coumarins, which are considered a significant group natural compounds their noteworthy anti-inflammatory properties. present study evaluated the activity dichloromethane methanolic extracts from H. paphlagonicum, sphondylium subsp. ternatum, elegans, cyclocarpum (100 mg/kg), have not previously investigated Inflammation models induced by carrageenan, prostaglandin E2, serotonin were employed to evaluate activity, using indomethacin (10 mg/kg) reference standard. Statistical differences between treatment control groups ANOVA with Student-Newman-Keuls post-hoc tests. Additionally, coumarin contents quantified mg/g high-performance liquid chromatography. roots displayed highest inhibition serotonin-induced hind paw edema, ranges 22.8%-36.9%, 5.4%-35.7%, 3.9%-17.9%, respectively, while 12.8%-44.3%, 2.7%-41.3%, 7.1%-30.6%, respectively. bergapten imperatorin quantities found in (0.49% 0.14%) elegans roots, had xanthotoxin level (0.06%). Angelicin was detected at concentrations 0.04%, 0.02%, correlation inhibitory observed elevated levels particularly imperatorin, suggests potential link concentration effects. our findings support traditional use this treating disorders. Further investigations necessary identify active elucidate mechanisms action these plants, potentially leading discovery novel therapeutic options inflammation.

Language: Английский

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Characterization and In-vitro Release of Coumarin from Folic Acid-Conjugated Mesoporous Silica for Targeted Cancer Therapy

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141502 - 141502

Published: Jan. 1, 2025

Language: Английский

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Zebrafish as a Suitable Model for Utilizing the Bioactivity of Coumarins and Coumarin-Based Compounds

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1444 - 1444

Published: Feb. 8, 2025

The aim of this review is to summarize the current knowledge on use coumarin-derived compounds in zebrafish (Danio rerio) model. Coumarins, a class naturally occurring with diverse biological activities, including such as coumarin, angelicin, and warfarin, have attracted considerable attention study potential therapeutic agents for cancer, central nervous system disorders, infectious diseases. capabilities coumarins active led synthesizing various derivatives their own properties. While variety certainly promising, it also cumbersome due large amount research needed find most optimal compounds. model offers unique advantages studies, high genetic physiological homology mammals, optical transparency embryos, rapid developmental processes, facilitating assessment compound toxicity underlying mechanisms action. This provides an in-depth analysis chemical properties coumarins, activity, results previous studies evaluating efficacy these assays. allows holistic coumarin derivatives, offering valuable insights advancing drug discovery development.

Language: Английский

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Umbelliferone and Its Synthetic Derivatives as Suitable Molecules for the Development of Agents with Biological Activities: A Review of Their Pharmacological and Therapeutic Potential

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(12), P. 1732 - 1732

Published: Dec. 15, 2023

Umbelliferone (UMB), known as 7-hydroxycoumarin, hydrangine, or skimmetine, is a naturally occurring coumarin in the plant kingdom, mainly from Umbelliferae family that possesses wide variety of pharmacological properties. In addition, use nanoparticles containing umbelliferone may improve anti-inflammatory anticancer therapy. Also, its derivatives are endowed with great potential for therapeutic applications due to their broad spectrum biological activities such anti-inflammatory, antioxidant, neuroprotective, antipsychotic, antiepileptic, antidiabetic, antimicrobial, antiviral, and antiproliferative effects. Moreover, 7-hydroxycoumarin ligands have been implemented develop 7-hydroxycoumarin-based metal complexes improved activity. Besides applications, analogues designed fluorescent probes detection biologically important species, enzymes, lysosomes, endosomes, monitoring cell processes protein functions well various diseases caused by an excess hydrogen peroxide. Furthermore, 7-hydroxy-based chemosensors serve highly selective tool Al3+ Hg2+ systems. This review devoted summary research on synthetic terms pharmaceutical properties, especially those reported literature during period 2017-2023. Future presented.

Language: Английский

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Beyond Mortality: Exploring the Influence of Plant Phenolics on Modulating Ferroptosis—A Systematic Review

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 334 - 334

Published: March 10, 2024

Ferroptosis is a recently discovered type of programmed cell death that mechanistically different from other types such as apoptosis, necroptosis, and autophagy. It characterized by the accumulation intracellular iron, overproduction reactive oxygen species, depletion glutathione, extensive lipid peroxidation lipids in membrane. was ferroptosis interconnected with many diseases, neurodegenerative ischemia/reperfusion injury, cancer, chronic kidney disease. Polyphenols, plant secondary metabolites known for bioactivities, are being extensively researched context their influence on which resulted great number publications showing need systematic review. In this review, an literature search performed. Databases (Scopus, Web Science, PubMed, ScienceDirect, Springer) were searched time span 2017 to November 2023, using keyword “ferroptosis” alone combination “flavonoid”, “phenolic acid”, “stilbene”, “coumarin”, “anthraquinone”, “chalcone”; after selection studies, we had 311 papers 143 phenolic compounds. total, 53 compounds showed ability induce ferroptosis, 110 able inhibit out those compounds, 20 both abilities depending model system. The most shikonin, curcumin, quercetin, resveratrol, baicalin. common modes action modulation Nrf2/GPX4 Nrf2/HO-1 axis iron metabolism.

Language: Английский

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Coumarins and flavones from Ficus erecta and their anti-inflammatory activity

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 333, P. 118472 - 118472

Published: June 19, 2024

Ficus erecta, a traditional Chinese She Ethnomedicine, has been historically utilized to treat various inflammatory conditions such as arthritis, nephritis, and osteoporosis. However, the underlying mechanisms accounting for its anti-inflammatory activity, well active components, largely remain elusive. The purpose of this research was investigate chemical constituents F. erecta that contribute effects. Coumarins flavones were obtained from 95% EtOH extract using virous column chromatography reversed-phase semipreparative HPLC. structures new compounds elucidated by extensive analysis spectroscopic methods, including HRESIMS, 1D 2D NMR spectra, CD experiments. Cultured macrophage RAW264.7 cells MTT cell viability assay, Griess reagent method, ELISA, Western blot experiments employed evaluate activity related mechanism. Four (1–4) eleven previously identified (5–16) coumarins, together with one (17) six known (18–23) isolated whole plant erecta. Compounds 7 17 significantly reduced nitric oxide (NO) prostaglandin E2 (PGE2) production without cytotoxic Furthermore, proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 in concentration-dependent manner. indicated suppressed expression iNOS, COX-2, p-IκBα LPS-stimulated cells. current phytochemical investigations revealed coumarins represent primary exhibit potent properties, linked inhibition NF-κB activation preventing degradation IκBα phosphorylation. These may serve promising candidates treating or certain diseases.

Language: Английский

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