Platycodon grandiflorum (PG) has been widely applied as a conductant drug by ancient and modern traditional Chinese medicine practitioners during long-term clinical practice. However, determining how to guide other medicines to the targeted lungs in traditional Chinese medicine (TCM) prescription remains unclear. An ethanol soluble fraction (Fr. B) was obtained by macroporous resin and 75 % ethanol precipitate. The components were unambiguously determined as fructooligosaccharides and small molecule weight (Mw) fructans according to HILIC-ESI--MS/MS, MS/MS and 1/2D NMR. We discovered that the Fr. B possesses the lung-oriented guidance and targetability by activating Golgi apparatus and endoplasmic reticulum (Golgi-ER) transport system. Rab21, a highly expressed transmembrane protein in the lungs, was found to be the core-affinity target of Fr. B which physically colocalized with the Golgi-ER and directly interacted with Rab21 to accelerate the uptake of extracellular therapeutic substances. The lung-oriented guidance and targetability of Fr. B was validated by the transient knockdown and overexpression of Rab21 considering dynamic observations of colocalization interactions among Fr. B, extracellular substances, and the Golgi-ER. Together, our results delineate a potential mechanism of Fr. B toward lung-oriented guidance and targetability via a direct targeting affinity of Rab21 and resulting collective stimulation of key Golgi-ER transport effectors for the acceleration of extracellular substances into the lungs.
Keywords: Fructans; Fructooligosaccharides; Golgi-ER transport system; Lung-oriented and targetability; Platycodon grandiflorum; Rab21.
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