Salvia miltiorrhiza Bunge extracts, known for their diverse biological activities, often have remarkable efficacy in treating pulmonary diseases overlooked due to their specific cardiovascular actions. With the recent outbreak of COVID-19, research into pulmonary-related diseases has garnered significant attention. Salvia miltiorrhiza Bunge extracts can be broadly categorized into lipophilic and hydrophilic components; however, a comprehensive summary of their mechanisms in treating pulmonary diseases is lacking. Therefore, this review aims to systematically summarize the therapeutic mechanisms of 10 major Salvia miltiorrhiza Bunge extracts in treating pulmonary fibrosis, lung cancer, acute lung injury, and chronic obstructive pulmonary disease, with the goal of identifying promising options for efficacious therapies.

Background: While neutrophil extracellular traps (NETs) have been shown to contribute to cancer progression, including that of lung adenocarcinoma, the mechanisms underlying NET formation within the tumor immune microenvironment (TIME) remain incompletely understood. Notably, neutrophil infiltration has been strongly linked to tumor necrosis factor alpha-inducible protein 6 (TNFAIP6) expression. Methods: In vitro and in vivo experiments were performed. DNA pulldown coupled with mass spectrometry, bioinformatics analyses, immunohistochemistry, and dual-luciferase reporter assays were conducted. DNA pulldown Western blotting, chromatin immunoprecipitation–quantitative PCR, and dual-luciferase reporter assays using truncated promoter constructs were also employed. Results: TNFAIP6 expressed by lung adenocarcinoma cells was shown to induce NET formation (a form of programmed cell death called NETosis). Mechanistically, TNFAIP6 interacted with CD44 in lung adenocarcinoma cells, leading to increased extracellular availability of secreted phosphoprotein 1 (SPP1) within the TIME and the subsequent promotion of NETosis. Additionally, nucleophosmin 1 (NPM1) significantly enhances the transcriptional activation of TNFAIP6 and associates with the −2000 to −1700 bp region of its promoter. Conclusions: These findings delineate a regulatory model in which lung adenocarcinoma cells directly stimulate NETosis through the NPM1–TNFAIP6–CD44–SPP1 axis, suggesting that therapeutic targeting of this pathway may attenuate tumor progression.

Dihydrosanguinarine (DHSA) is a naturally occurring benzo[c]phenanthridine alkaloid primarily isolated from plants of the Papaveraceae family. DHSA exhibits broad pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, neuroprotective, analgesic, anxiolytic, antiarrhythmic, and antimicrobial effects. Mechanistically, DHSA regulates multiple signaling pathways and molecular targets, including TMEM16A, p53, Ras/Raf/MEK/ERK, PI3K/AKT, NF-κB, PPARγ, GABA_A receptors, and voltage-gated sodium channels. Compared with its biosynthetic precursor sanguinarine (SA), DHSA exhibits a comparatively favorable safety profile while retaining considerable biological activity. Pharmacokinetic studies further suggest that DHSA possesses acceptable membrane permeability, gastrointestinal absorption potential, enterohepatic circulation characteristics, and sustained systemic exposure. In addition, structure–activity relationship (SAR) and electrostatic surface potential (ESP) analyses indicate that the chemically accessible C6 position may provide opportunities for rational structural optimization. Nevertheless, the clinical translation of DHSA still faces several challenges. Therefore, this review systematically summarizes the physicochemical properties, pharmacological activities, molecular mechanisms, SAR characteristics, ESP distribution, toxicity, pharmacokinetic behavior, and clinical prospects of DHSA, aiming to provide a theoretical basis for its future drug development and translational application.

Proximity labeling (PL) enables covalent capture of biomolecules near a defined target in living systems, providing a route to map molecular proximity in situ. Conventional PL usually relies on a single targeting cue and may therefore lack the selectivity required to resolve defined molecular events or dynamic processes in complex biological systems. Conditional PL addresses this limitation by coupling labeling activity to additional inputs, including interaction-dependent enzyme reconstitution, localization of catalytic modules at cell–cell interfaces, light-regulated catalysis, and multiple orthogonal labeling reactions. These designs allow labeling to respond to specified spatial, temporal, or molecular conditions. We group conditional PL into four designs—split complementation, interface localization, light control, and multiple labeling—based on what activates labeling and what the labels reveal. We examine their use in studying protein complexes, trafficking, and intercellular communication. We also consider what each strategy encodes, the experimental boundaries of the resulting proximity information, and trade-offs among selectivity, labeling efficiency, temporal control, and compatibility with native biological contexts. Remaining challenges include expanding catalyst and probe diversity, improving in vivo compatibility, and integrating conditional PL with single-cell analysis, spatial omics, and high-resolution imaging.