High-Altitude Pulmonary Edema (HAPE) represents a life-threatening form of non-cardiogenic pulmonary edema triggered by rapid ascent to altitudes above 2500 meters. The precise pathogenesis remains incompletely elucidated

but the hypobaric hypoxia (HH) environment is universally acknowledged as the initiating factor. Within the complex pathophysiological cascade

the Hypoxia-Inducible Factor-1α (HIF-1α)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling axis has recently emerged as a critical convergence point driving inflammatory injury

vascular leakage

and oxidative stress. HIF-1α

a master transcriptional regulator of cellular adaptation to hypoxia

activates under low oxygen tension

upregulating genes involved in inflammation

vascular permeability

and pulmonary hypertension. Concurrently

it potently activates the NLRP3 inflammasome

leading to Caspase-1 activation and the maturation of potent pro-inflammatory cytokines IL-1β and IL-18

thereby amplifying a local "inflammatory storm" within the lung parenchyma. Modern pharmacological interventions for HAPE are limited

primarily targeting symptoms like pulmonary hypertension

and lack specific agents addressing this core inflammatory pathway. In contrast

Traditional Chinese Medicine (TCM)

with its holistic philosophy and multi-component

multi-target therapeutic characteristics

shows promising potential in modulating the HIF-1α/NLRP3 axis. This review systematically summarizes the mechanistic roles of the HIF-1α/NLRP3 pathway in HAPE pathogenesis

elaborates on the theoretical foundations of TCM in understanding and treating HAPE-like disorders (categorized under "Fei Zhang" or lung distension)

and compiles contemporary evidence on how specific Chinese herbal medicines and their active compounds exert protective effects by inhibiting this signaling pathway. Furthermore

it discusses the current limitations and future directions for integrating TCM with modern biomedical research to develop more effective strategies for HAPE prevention and treatment. Exploring the regulatory effects of TCM on the HIF-1α/NLRP3 pathway not only provides a modern scientific interpretation for its efficacy but also opens new avenues for discovering novel therapeutic agents.