Jingfang Baidu San Alleviates Feng-Han (Wind-Cold) Syndrome-Associated Lung Injury in Mice Through Macrophage Functional Regulation and Dectin-1-Associated Immune Remodeling.

ETHNOPHARMACOLOGICAL RELEVANCE: Jingfang Baidu San (JF) is a classic traditional Chinese medicine(TCM)formula that has been widely used in clinical practice for hundreds of years. While its efficacy in treating Feng Han (wind-cold, FH) common cold has garnered increasing attention, its underlying mechanism of action remain incompletely understood.

AIM: This study aimed to evaluate the therapeutic effect of JF on wind-cold common cold and to elucidate its molecular mechanism.

METHODS: A mouse model of wind-cold syndrome (FH) was established by exposing mice to wind and cold stress for 7 consecutive days. The therapeutic effects of orally administered JF were initially evaluated by assessing behavioral manifestations, body weight, and rectal temperature. Lung histopathology was subsequently examined using hematoxylin and eosin (H&E) staining. To investigate the potential molecular mechanisms underlying the effects of JF on FH, transcriptomic sequencing of lung tissues was performed to identify key differentially expressed genes and associated regulatory networks. Inflammatory cytokine levels in serum and lung tissues were further quantified using enzyme-linked immunosorbent assays (ELISA), while the expression and localization of key molecular targets and related proteins were validated by immunofluorescence staining, immunohistochemistry, and Western blotting.

RESULTS: JF significantly ameliorated the major pathological manifestations in FH model mice, as evidenced by body weight recovery, reduction of elevated rectal temperature, and improvement of behavioral abnormalities including lethargy, hypoactivity, and respiratory abnormalities. Histopathological analysis further confirmed that JF markedly alleviated lung tissue injury and reduced the levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α in serum and lung tissue. At the mechanistic level, through transcriptomic analysis combined with in vivo validation, we identified Dectin-1 Clec7a as a potential macrophage-related regulatory node associated with the efficacy of JF in treating FH. JF treatment restored the expression of macrophage-associated Dectin-1, while attenuating macrophage-associated inflammatory responses and tissue remodeling responses. In conclusion, the protective effect of JF against FH-related lung injury is associated with the regulation of macrophage Dectin-1, inhibition of NF-κB activation, and attenuation of TGF-β-related responses, inflammatory responses, and abnormal extracellular matrix remodeling.

CONCLUSION: The protective effects of JF against FH-induced lung injury were associated with modulation of macrophage Dectin-1 expression, suppression of NF-κB activation, and attenuation of TGF-β-related signaling, accompanied by reduced inflammation and amelioration of aberrant extracellular matrix remodeling. These findings suggest that Dectin-1-mediated macrophage regulation may contribute to the protective effects of JF. Further genetic and pharmacological studies are needed to establish the causal roles of Dectin-1, NF-κB, and TGF-β-related signaling pathways in mediating the effects of JF.