Tetrastigma hemsleyanum polysaccharide protects against "two-hit" induced severe pneumonia via TLR4/NF-κB signaling pathway.

Severe pneumonia, frequently accompanied by cytokine storms, stands as a perilous respiratory condition with alarmingly high mortality rates. Tetrastigma hemsleyanum polysaccharide (THP), a pivotal constituent derived from Tetrastigma hemsleyanum Diels et Gilg (TH), has demonstrated efficacy in treating lung inflammation. However, its precise efficacy and underlying mechanisms in the context of severe pneumonia remain elusive. Our research aims to elucidate THP's protective effects in a "two-hit" severe pneumonia model. Our observations indicate that THP administration markedly shields the lungs from injury, reduces pulmonary apoptosis, balances the formation of immune thrombus and alleviates oxidative stress in pneumonia-induced mice. Furthermore, THP significantly decreases the levels of pro-inflammatory cytokines, suggesting its robust anti-inflammatory capabilities. Notably, THP also plays a crucial role in normalizing gut microbiota imbalance, which is vital in the pathogenesis of severe pneumonia. Metabolomic analysis further validates THP's restorative effects on plasma metabolites, indicating its involvement in regulating energy metabolism and immune homeostasis. Mechanistically, THP targets the TLR4/NF-κB signaling pathway, a core mediator of inflammation, thereby dampening the inflammatory cascade. In summary, our findings underscore that THP, through its multifaceted actions targeting inflammation, oxidative stress, immune thrombus formation, gut microbiota regulation, and metabolic modulation, emerges as a promising therapeutic approach for severe pneumonia. This study provides invaluable insights into the potential applications of natural polysaccharides in treating severe pneumonia and highlights the significance of the TLR4/NF-κB pathway in the disease's progression.