2. Academic Validation
  3. Panduratin A Induces Autophagy Through AMPK Activation Independent of mTOR Inhibition and Restricts Mycobacterium tuberculosis in Host Macrophages

Panduratin A Induces Autophagy Through AMPK Activation Independent of mTOR Inhibition and Restricts Mycobacterium tuberculosis in Host Macrophages

  • Mol Microbiol. 2025 Dec;124(6):491-506. doi: 10.1111/mmi.70025.
Thomanai Lamtha 1,  Olabisi Flora Davies-Bolorunduro 1 2 3,  Sureeporn Phlaetita 1,  Chernkhwan Kaofai 1,  Phongthon Kanjanasirirat 4,  Tanawadee Khumpanied 5,  Napason Chabang 6,  Bamroong Munyoo 5,  Patoomratana Tuchinda 5,  Suparerk Borwornpinyo 5 7,  Supawan Jamnongsong 8,  Somponnat Sampattavanich 8,  Prasit Palittapongarnpim 1 2,  Marisa Ponpuak 1
Affiliations

Affiliations

  • 1 Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 2 Pornchai Matangkasombut Center for Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 3 Floret Center for Advanced Genomics and Bioinformatics Research, Lagos, Nigeria.
  • 4 Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 5 Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 6 School of Bioinnovation and Bio-Based Product Intelligence, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 7 Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand.
  • 8 Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
PMID: 41001742 DOI: 10.1111/mmi.70025
Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health burden, especially with the increasing prevalence of drug-resistant strains. There is an urgent need for new therapeutics that act via alternative mechanisms. Autophagy, a vital cell-autonomous defense process, allows macrophages to degrade intracellular pathogens such as Mtb and has gained attention as a potential target for host-directed therapy. In this study, we conducted a high-content imaging screen of herb-derived compounds to identify Autophagy inducers in RAW264.7 macrophages. Panduratin A (NPA), a natural compound from Boesenbergia rotunda, was found to potently induce Autophagy. NPA promoted autophagic vacuole formation in a dose-dependent fashion at low micromolar levels. Its autophagy-inducing effect was validated using RFP-GFP-LC3 dual fluorescence assays and immunoblotting in the presence of bafilomycin A1. Further mechanistic analysis revealed that NPA activates Autophagy through AMPK activation, independent of mTOR inhibition. Importantly, NPA significantly promoted intracellular Mtb clearance and increased colocalization of Mtb with autophagosomes and lysosomes, in a manner dependent on Beclin-1. These findings highlight NPA as a potent enhancer of macrophage antimicrobial responses via Autophagy, supporting its potential as a candidate for host-directed adjunctive therapy against TB.

Keywords

Boesenbergia rotunda; Panduratin A; autophagy; tuberculosis.

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