[Supramolecular differences and pulmonary protective activity of Forsythiae Fructus-Lonicerae Japonicae Flos herb pair prepared with green Forsythiae Fructus and ripe Forsythiae Fructus].

This study aimed to investigate the supramolecular differences arising from the herb pair Forsythiae Fructus-Lonicerae Japonicae Flos(LF) prepared with green Forsythiae Fructus( GF) versus ripe Forsythiae Fructus( RF), and to elucidate their respective pulmonary protective activities. The macroscopic morphology, chemical composition, and in vitro biological activities including antibacterial, antioxidant, and anti-fibrotic effects(specifically the inhibition of TGF-β1-induced fibroblast hyperproliferation and collagen deposition) were systematically compared between GF-LF and RF-LF co-decoctions. The results revealed significant morphological distinctions: the GF-LF co-decoction exhibited higher turbidity and self-assembled spherical supramolecular particles with a diameter of approximately 1 μm, whereas the RF-LF co-decoction formed smaller particles with a diameter ranging from 400 to 600 nm. HPLC and UPLC-MS/MS analyses indicated that both co-decoctions exhibited qualitatively similar phytochemical profiles. However, quantitative differences were evident: GF-LF showed higher content of forsythoside A, phillyrin, and rutin, while RF-LF exhibited higher levels of chlorogenic acid and phillygenin. Biological activity assays demonstrated that GF-LF possessed significantly stronger antibacterial, antioxidant, and anti-fibrotic activities than RF-LF. This study reveals, at the supramolecular level, that the differences in component content between GF and RF drive distinct self-assembly behaviors in the decocting with LF, consequently influencing their pulmonary protective efficacy. These findings provide an experimental basis for the rational clinical selection of Forsythiae Fructus specifications.