ArticleNature communications2023
Natural product P57 induces hypothermia through targeting pyridoxal kinase.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
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- Target discovery-directed pharmacological mechanism elucidation of bioactive natural products.Medical review (2021) · 2025Review
- Total Synthesis of Cardenolides Acospectoside A and Acovenoside B.Molecules (Basel, Switzerland) · 2025Article
- Intermittent fasting inhibits platelet activation and thrombosis through the intestinal metabolite indole-3-propionate.Life metabolism · 2025Article
- Recent Advances in Natural Products Derived from Marine Echinoderms and Endophytic Microbes: Chemical Insights and Therapeutic Potential.Marine drugs · 2025Review
Corrections and comments
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Authors and funding
31 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hypothermia in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in mice. Mechanistically, P57 inhibits the kinase activity of pyridoxal kinase (PDXK), a key metabolic enzyme of vitamin B6 catalyzing phosphorylation of pyridoxal (PL), resulting in the accumulation of PL in hypothalamus to cause hypothermia. The hypothermia induced by P57 is significantly blunted in the mice with knockout of PDXK in the preoptic area (POA) of hypothalamus. We further found that P57 and PL have consistent effects on gene expression regulation in hypothalamus, and they may activate medial preoptic area (MPA) neurons in POA to induce hypothermia. Taken together, our findings demonstrate that P57 has a potential application in therapeutic hypothermia through regulation of vitamin B6 metabolism and PDXK serves as a previously unknown target of P57 in thermoregulation. In addition, P57 may serve as a chemical probe for exploring the neuron circuitry related to hypothermia state in mice.
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