Immunoregulation by Artemisinin and Its Derivatives: A New Role for Old Antimalarial Drugs

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 9, 2021

Artemisinin and its derivatives (ARTs) are known as conventional antimalarial drugs with clinical safety efficacy. Youyou Tu was awarded a Nobel Prize in Physiology Medicine due to her discovery of artemisinin therapeutic effects on malaria. Apart from effects, mounting evidence has demonstrated that ARTs exert inflammation autoimmune disorders because their anti-inflammatory immunoregulatory properties. In this aspect, tremendous progress been made during the past five seven years. Therefore, present review summarizes recent studies have explored immunomodulatory diseases transplant rejection. review, we also discuss cellular molecular mechanisms underlying ARTs. Recent preclinical will help lay groundwork for trials using treat various immune-based disorders, especially diseases.

Language: Английский

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Methyl jasmonate elicitation improved growth, antioxidant enzymes, and artemisinin content in in vitro callus cultures of Artemisia maritima L.

South African Journal of Botany, Journal Year: 2025, Volume and Issue: 177, P. 729 - 741

Published: Jan. 10, 2025

Language: Английский

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Computable properties of selected monomeric acylphloroglucinols with anticancer and/or antimalarial activities and first-approximation docking study

Journal of Molecular Modeling, Journal Year: 2025, Volume and Issue: 31(4)

Published: March 12, 2025

Abstract Context Malaria and cancer tend to become drug-resistant a few years after drug is introduced into clinical use. This prompts the search for new molecular structures that are sufficiently different from drugs which resistance has developed. The present work considers eight selected acylphloroglucinols (ACPLs) with proven antimalarial and/or anticancer activities. ACPLs compounds of natural origin structurally derivative 1,3,5-trihydroxybenzene characterized by presence an acyl group R–C = O. contain only one acylphloroglucinol moiety are, therefore, monomeric (also occasionally called “simple” ACPLs). They were studied computationally in vacuo in-three-solvents polarities, using levels theory. findings on properties relevant understanding biological activities align previous studies, enhancing reliability predictions molecules same class providing insights their behaviour environments. Structure-based virtual screening was used study interactions between these proteins known as targets activities; showed most bind well proteins, thus being interesting further studies. results also suggest have potential dual therapeutic applications (antimalarial anticancer), offering cost-effective development option. Furthermore, ADME-T indicated favourable pharmacokinetic ACPLs. Methods Computational studies performed Gaussian-09, polarities. Three theory – Hartree Fock (HF), Density Functional Theory (DFT) B3LYP functional, second order Møller-Plesset Perturbation (MP2). HF MP2 6-31G(d,p) basis set, while DFT 6-31G + (d,p), consistency investigated include conformational preferences, intramolecular hydrogen bonding patterns, HOMO–LUMO energy gap, dipole moments, solvent effect three considered solvents. Virtual conducted Schrödinger suite, including Maestro 9.3 GLIDE docking GlideScore evaluating binding affinities. In addition, QikProp tool provided properties.

Language: Английский

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Artesunate Suppresses the Migration and Invasion of Thyroid Cancer Cells via Upregulating PTEN to Block M2 Polarization of Tumor‐Associated Macrophages

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(3)

Published: March 1, 2025

ABSTRACT Immunotherapy holds promise for thyroid cancer (TC) treatment. In the context of our previous findings that artesunate (ART) could inhibit migration and invasion TC cells through phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt), this study was engineered to investigate whether ART regulates tumor microenvironment in TC. THP‐1 were differentiated into M0 macrophages by induction 100 ng/mL phorbol 12‐myristate 13‐acetate transfected as needed. treated with different concentrations (10 20 μM) 24 h. The co‐culture conducted. Flow cytometry enzyme‐linked immunosorbent assay used identify M2 macrophages. viability, migration, detected cell counting kit‐8, wound healing, transwell assays. mRNA or protein expressions examined genes measured quantitative real‐time polymerase chain reaction Western blot. co‐cultured macrophages, CD206, CD163, Arginase‐1, well secretion IL‐10 CCL18, promoted, but phosphatase tensin homolog (PTEN) expression inhibited, which reversed ART. system, μM downregulated Arginase‐1 diminished invasion, ratios p‐PI3K/PI3K p‐Akt/Akt cells, offset PTEN deletion Collectively, suppresses via inhibiting PI3K/Akt pathway upregulation‐blocked polarization tumor‐associated

Language: Английский

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Applications of Bridgehead Heterocycles in Drug Design and Medicinal Chemistry

Topics in Current Chemistry, Journal Year: 2025, Volume and Issue: 383(2)

Published: March 21, 2025

Language: Английский

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Development and Evaluation of Polyvinylpyrrolidone K90 and Poloxamer 407 Self-Assembled Nanomicelles: Enhanced Topical Ocular Delivery of Artemisinin

Polymers, Journal Year: 2021, Volume and Issue: 13(18), P. 3038 - 3038

Published: Sept. 8, 2021

Age-related macular degeneration is a multifactorial disease affecting the posterior segment of eye and characterized by aberrant nascent blood vessels that leak fluid. It ends with vision loss. In present study, artemisinin which poorly water-soluble has potent anti-angiogenic anti-inflammatory properties was formulated into nanomicelles for its ocular application activity using CAM assay. Artemisinin-loaded were prepared varying concentrations PVP k90 poloxamer 407 at different ratios showed spherical shape particles in size range 41–51 nm. The transparency cloud point developed artemisinin-loaded found to be 99–94% 68–70 °C, respectively. vitro release from 96.0–99.0% within 8 h. trans-corneal permeation studies exhibited 1.717–2.169 µg through excised rabbit cornea 2 Drug-free did not exhibit noticeable DNA damage an acceptable level hemolytic potential. remarkable compared suspension. Hence, might have potential treatment AMD.

Language: Английский

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RETRACTED: Artemisia Extracts and Artemisinin-Based Antimalarials for COVID-19 Management: Could These Be Effective Antivirals for COVID-19 Treatment?

Molecules, Journal Year: 2022, Volume and Issue: 27(12), P. 3828 - 3828

Published: June 14, 2022

As the world desperately searches for ways to treat coronavirus disease 2019 (COVID-19) pandemic, a growing number of people are turning herbal remedies. The Artemisia species, such as A. annua and afra, in particular, exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection COVID-19 related symptoms. is source artemisinin, which active malaria, also exhibits potential other diseases. This has increased interest artemisinin’s drug repurposing. Artemisinin-based combination therapies, so-called ACTs, have already been recognized first-line treatments malaria. extract, well demonstrated inhibition SARS-CoV-2. Artemisinin its derivatives shown anti-inflammatory effects, including interleukin-6 (IL-6) that plays key role development COVID-19. There now sufficient evidence literature suggest effectiveness Artemisia, constituents and/or artemisinin derivatives, fight SARS-CoV-2 by inhibiting invasion, replication, reducing oxidative stress inflammation, mitigating lung damage.

Language: Английский

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Artesunate alleviates 5-fluorouracil-induced intestinal damage by suppressing cellular senescence and enhances its antitumor activity

Discover Oncology, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 27, 2023

Colorectal cancer (CRC) is one of the most prevalent diagnosed malignancies and leading causes cancer-related deaths worldwide. 5-Fluorouracil (5-FU) its combination regimen are commonly used as primary chemotherapeutic agents for advanced CRC. Intestinal mucositis frequent side effects 5-FU. Artesunate (Arte) derived from wormwood plant Artemisia annua. Arte not only effective against malaria but also diabetes, atherosclerosis, inflammation, other conditions. The mechanism by which 5-FU damages intestinal tract unclear, there no standard treatment diarrhea caused Therefore, it critical to discover novel promising therapeutic drugs effect treatment.The morphology expression genes proteins associated with aging HUVECs, HIECs, tissues were compared those control group. cell lines evaluated SA-β-Gal staining, Western blotting, RT‒qPCR. HIEC HCT116 viability was assessed in vitro a CCK-8 assay vivo subcutaneous tumor mouse assay. Tumor proliferation apoptosis immunohistochemistry.Here, we report that alleviates adverse tissue, 5-FU-induced damage drug-induced chemical inflammation an increase proportion senescent cells. decreases ratio SA-β-Gal-positive cells downregulated aging-related (p53, p16) p21). Mechanistically, relieves injury inhibiting mTOR expression, regulation aging. Moreover, suppresses p38MAPK NF-κB signaling pathways, related regulation. In addition, combined therapy plus significantly vitro. synergistically reduce growth colorectal xenografts vivo.Overall, our findings point crucial on senescence, CRC offer new option treatment.

Language: Английский

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An overview on the antimalarial activity of 1,2,4‐trioxanes, 1,2,4‐trioxolanes and 1,2,4,5‐tetraoxanes

Medicinal Research Reviews, Journal Year: 2023, Volume and Issue: 44(1), P. 66 - 137

Published: May 24, 2023

Abstract The demand for novel, fast‐acting, and effective antimalarial medications is increasing exponentially. Multidrug resistant forms of malarial parasites, which are rapidly spreading, pose a serious threat to global health. Drug resistance has been addressed using variety strategies, such as targeted therapies, the hybrid drug idea, development advanced analogues pre‐existing drugs, model strains control mechanisms. Additionally, discovering new potent drugs grows due prolonged life cycle conventional therapy brought on by emergence ongoing changes in existing therapies. 1,2,4‐trioxane ring system artemisinin (ART) most significant endoperoxide structural scaffold thought be key pharmacophoric moiety required pharmacodynamic potential endoperoxide‐based antimalarials. Several derivatives have also found treatments multidrug‐resistant strain this area. Many 1,2,4‐trioxanes, 1,2,4‐trioxolanes, 1,2,4,5‐tetraoxanes synthesised result, many these shown promise activity both vivo vitro against Plasmodium parasites. As consequence, efforts develop functionally straight‐forward, less expensive, vastly more synthetic pathway trioxanes continue. This study aims give thorough examination biological properties mode action compounds derived from 1,2,4‐trioxane‐based functional scaffolds. present 1,2,4‐trioxane, 1,2,4‐trioxolane, 1,2,4,5‐tetraoxane dimers with potentially will highlighted systematic review (January 1963–December 2022).

Language: Английский

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Anti-malarial activity of the alkaloid, heptaphylline, and the furanocoumarin, imperatorin, from Clausena anisata against human Plasmodium falciparum malaria parasites: ex vivo trophozoitocidal, schizonticidal and gametocytocidal approach

Malaria Journal, Journal Year: 2023, Volume and Issue: 22(1)

Published: Sept. 9, 2023

The erythrocytic stage of the life cycle malaria parasite, Plasmodium falciparum, consists trophozoite, schizont and gametocyte stages in humans. Various anti-malarial agents target different parasite to produce treatment outcomes. This study reports on stage-specific activity heptaphylline imperatorin against human P. falciparum addition their cytotoxicity selectivity indices (SI).The compounds were isolated from Clausena anisata using column chromatography structures elucidated NMR spectroscopy. was determined by measuring trophozoitocidal, schizonticidal gametocytocidal activities SYBR green assay. Cytotoxicity evaluated tetrazolium-based colorimetric assay.Heptaphylline produced with IC50s 1.57 (0.2317)-26.92 (0.3144) µM those artesunate (the standard drug) being 0.00024 (0.0036)-0.0070 (0.0013) µM. In assay, CC50S greater than 350 SI 13.76-235.90. Also, trophozoitocidal more pronounced activity. Imperatorin 42.04% hepthaphyline. However, hepthaphyline has properties imperatorin.Heptaphylline are promising agents, since they possess potent weak RBCs. is a better prophylactic agent whereas agent.

Language: Английский

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