ArticleEMBO molecular medicine2012
The lignan niranthin poisons Leishmania donovani topoisomerase IB and favours a Th1 immune response in mice.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 70 citations in OpenAlex.
- Kinetoplast-Directed Therapies: A Selective Mitochondrial Approach to Combat Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2026Review
- [Niranthin ameliorates Crohn's disease-like colitis in mice via antagonizing intestinal epithelial cell apoptosis and regulating intestinal Th1/Th2 immune homeostasis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Natural product-based therapeutic strategies againstFrontiers in microbiology · 2026Review
- [Niranthin ameliorates Crohn's disease-like enteritis in mice by inhibiting intestinal epithelial cell apoptosis and protecting intestinal barrierNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Herbal Immunostimulants and Their Phytochemicals: ExploringPlants (Basel, Switzerland) · 2025Review
- NADPHnet: a novel strategy to predict compounds for regulation of NADPH metabolism via network-based methods.Acta pharmacologica Sinica · 2024Article
- Asymmetric total synthesis of four bioactive lignans using donor-acceptor cyclopropanes and bioassay of (-)- and (+)-niranthin against hepatitis B and influenza viruses.RSC advances · 2022Article
- An insight into the potent medicinal plantThe Nucleus : an international journal of cytology and allied topics · 2022Review
- Identification of Anxiolytic Potential of Niranthin: In-vivo and Computational Investigations.Natural products and bioprospecting · 2021Article
- In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis.PLoS neglected tropical diseases · 2020Article
- Use of Natural Products in Leishmaniasis Chemotherapy: An Overview.Frontiers in chemistry · 2020Review
- Plant Phenolics as Pathogen-Carrier Immunogenicity Modulator Haptens.Current pharmaceutical biotechnology · 2020Review
- An Insight Into the Modulatory Effects and Mechanisms of Action ofFrontiers in pharmacology · 2019Review
- Ammonium trichloro [1,2-ethanediolato-O,O']-tellurate cures experimental visceral leishmaniasis by redox modulation of Leishmania donovani trypanothione reductase and inhibiting host integrin linked PI3K/Akt pathway.Cellular and molecular life sciences : CMLS · 2018Article
- Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis.Scientific reports · 2017Article
- Apoptosis-like cell death in Leishmania donovani treated with KalsomeTM10, a new liposomal amphotericin B.PloS one · 2017Article
- Immunotherapeutic Potential of Eugenol Emulsion in Experimental Visceral Leishmaniasis.PLoS neglected tropical diseases · 2016Article
- A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani Parasites both In Vitro and In Vivo by Targeting Type IB Topoisomerase.Antimicrobial agents and chemotherapy · 2016Article
- The Genus Phyllanthus: An Ethnopharmacological, Phytochemical, and Pharmacological Review.Evidence-based complementary and alternative medicine : eCAM · 2016Review
- Plant-derived compounds in treatment of leishmaniasis.Iranian journal of veterinary research · 2015Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Niranthin, a lignan isolated from the aerial parts of the plant Phyllanthus amarus, exhibits a wide spectrum of pharmacological activities. In the present study, we have shown for the first time that niranthin is a potent anti-leishmanial agent. The compound induces topoisomerase I-mediated DNA-protein adduct formation inside Leishmania cells and triggers apoptosis by activation of cellular nucleases. We also show that niranthin inhibits the relaxation activity of heterodimeric type IB topoisomerase of L. donovani and acts as a non-competitive inhibitor interacting with both subunits of the enzyme. Niranthin interacts with DNA-protein binary complexes and thus stabilizes the 'cleavable complex' formation and subsequently inhibits the religation of cleaved strand. The compound inhibits the proliferation of Leishmania amastigotes in infected cultured murine macrophages with limited cytotoxicity to the host cells and is effective against antimony-resistant Leishmania parasites by modulating upregulated P-glycoprotein on host macrophages. Importantly, besides its in vitro efficacy, niranthin treatment leads to a switch from a Th2- to a Th1-type immune response in infected BALB/c mice. The immune response causes production of nitric oxide, which results in almost complete clearance of the liver and splenic parasite burden after intraperitoneal or intramuscular administration of the drug. These findings can be exploited to develop niranthin as a new drug candidate against drug-resistant leishmaniasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.