Targeting Ferroptosis in Sepsis: Therapeutic Potential and Mechanisms of Natural Products and Traditional Chinese Medicine.

Sepsis is a life-threatening organ dysfunction driven by a dysregulated host response to infection, yet targeted pharmacological therapies remain severely limited. Emerging evidence highlights ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, as a pivotal mechanism underlying sepsis pathogenesis and subsequent multiple organ dysfunction syndrome (MODS). While the pathological relevance of ferroptosis is well-established, comprehensive reviews exploring the potential of Traditional Chinese Medicine (TCM) and natural bioactive compounds to therapeutically modulate this pathway in sepsis remain scarce. This review systematically evaluates diverse TCM-derived phytochemicals, including flavonoids, terpenoids, alkaloids, and polyphenols, elucidating their molecular mechanisms in attenuating sepsis-induced ferroptosis. Specifically, we detail how these natural products mitigate multi-organ injury by restoring iron homeostasis, quenching lipid peroxidation cascades, and upregulating core antioxidant axes, notably the Nrf2/SLC7A11/GPX4 signaling pathway. By synthesizing current preclinical evidence encompassing isolated bioactive compounds and classical TCM formulae, this review aims to clarify the pharmacological rationale of TCM in sepsis management, offering novel insights for the discovery of innovative therapeutic targets and the development of precision medicine strategies.