Covalent targeting GAPDH by Pudilan formula and baicalein suppresses macrophage Warburg effect to alleviate acute lung injury.

Researchers investigated how Pudilan (PDL), a traditional Chinese medicine formula, helps treat acute lung injury (ALI), a life-threatening inflammatory condition affecting the lungs. While PDL has been used clinically to treat inflammatory diseases, scientists didn't fully understand how it worked at the molecular level due to its complex mixture of plant compounds. Using advanced laboratory techniques, researchers discovered that PDL works by directly targeting a specific enzyme called GAPDH in immune cells called macrophages. They identified baicalein, a compound found in Chinese skullcap (a component of PDL), as the main active ingredient responsible for this effect. When baicalein binds to GAPDH, it changes how macrophages produce energy, shifting them away from an inflammatory state that worsens lung damage. The researchers tested this in both cell cultures and mice with lung injury, finding that both PDL and baicalein reduced inflammation and lung damage. This study is particularly relevant to acupuncture patients because it validates the scientific mechanisms behind traditional Chinese herbal medicine, which is often used alongside acupuncture in integrated treatment approaches. Many acupuncturists incorporate Chinese herbal formulas like Pudilan into their treatment plans for respiratory and inflammatory conditions. Understanding how these herbs work at the molecular level helps bridge traditional wisdom with modern medicine, supporting their therapeutic use. If you're considering acupuncture or Chinese herbal medicine for inflammatory conditions, seek a licensed acupuncturist or traditional Chinese medicine practitioner with appropriate credentials and training.

This study employed activity-based protein profiling (ABPP) chemoproteomics to identify direct molecular targets of Pudilan (PDL) formula in treating acute lung injury (ALI). Researchers discovered that PDL and its primary bioactive component baicalein covalently bind to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) at its catalytic cysteine residue (Cys150) in macrophages. This covalent modification inhibited GAPDH enzymatic activity, suppressing glycolytic flux (Warburg effect) and shifting macrophage metabolism toward oxidative phosphorylation. Functionally, this metabolic reprogramming reversed pro-inflammatory M1 macrophage polarization, suppressed NF-κB p65 nuclear translocation, and reduced inflammatory mediator production. In vivo validation using LPS-induced murine ALI models demonstrated that both PDL and baicalein significantly alleviated lung injury with confirmed GAPDH engagement in lung tissues. Clinical relevance: This mechanistic elucidation supports PDL's traditional use for inflammatory respiratory conditions and establishes a metabolism-immunity therapeutic axis, providing scientific rationale for incorporating PDL or baicalein-containing formulas in treating inflammatory lung pathologies.