"Targeting the Body Itself": Research Progress on the Anti-Inflammatory and Immunomodulatory Mechanisms of...

Pyroptosis is a highly inflammatory form of regulated cell death executed by gasdermin proteins. It promotes the release of interleukin (IL)-1β and IL-18 to support host defense, yet its dysregulation contributes to sepsis, neurodegenerative disorders, and autoimmune diseases. Many current anti-inflammatory therapies are single-target and may not restore system-level immune balance.

To summarize core pyroptosis pathways and evaluate how Traditional Chinese Medicine (TCM) modulates pyroptosis through multi-component, multi-target regulation.

We synthesize mechanistic evidence on canonical and non-canonical inflammasome cascades, focusing on caspase activation and Gasdermin D (GSDMD) cleavage. We further summarize data on representative TCM-derived compounds (berberine, curcumin, ginsenoside Rd) and a classical formula (Buyang Huanwu Decoction), emphasizing their actions on key pyroptosis nodes and upstream stress signals.

Pyroptosis is driven by inflammasome-dependent signaling that activates caspases, cleaves GSDMD, and triggers pore formation with inflammatory mediator release. Evidence suggests TCM interventions can attenuate pyroptosis by converging on NLRP3 inflammasome activation, NF-κB/STAT3 signaling, and mitochondrial reactive oxygen species, while formulas may provide broader antioxidant and intercellular regulatory effects.

TCM offers a systems-oriented strategy for pyroptosis-centered anti-inflammatory and immunomodulatory therapy.