Micro-PET Imaging Demonstrates 3-O-β-D-Glucopyranosyl Platycodigenin as an Effective Metabolite Affects Permeability of Cell Membrane and Improves Dosimetry of [18F]-Phillygenin in Lung Tissue

Abstract

Platycodon grandiflorum, as a traditional medicinal plant, is commonly used in the treatment of pulmonary disease. Platycodon saponins are proposed as active ingredients. However, the role of secondary saponin metabolites (SSM) in the traditional use of Platycodon has not yet been fully clarified. In this study, [18F]-phillygenin ([18F]-PH) probe was synthesized and thereby used as a tracer for micro-positron emission tomography scanning to explore the effects of platycodon saponins. The membrane permeability with different SSM was evaluated in vitro based on the dye-carrying capacity of fluorescein isothiocyanate. The results showed that total platycodon saponins improved the dosimetry of [18F]-PH in the lung tissue, and an SSM named 3-O-β-D-glucopyranosyl platycodigenin (GPD682) appreciably changed the distribution of drugs both in vitro and in vivo. We propose that GPD682 could be utilized as an important ingredient to help drug delivery to the lung tissue and improve the treatment of respiratory disease.

Micelles self-assembled by 3-O-β-D-glucopyranosyl latycodigenin enhances cell membrane permeability, promotes antibiotic pulmonary targeting and improves anti-infect efficacy

“…Therefore, a new strategy to reduce the use of high doses of antibiotics is needed. The active compound of 682 increases drug targeting in mice lung, 25 and GP-682 micelles effectively improved cellular uptake in vitro. To evaluate whether GP-682 micelles achieve higher lung tissue uptake in vivo, the concentration of levo oxacin in lung tissue was detected using HPLC with or without GP-682 micelle pretreatment for 30 min.…”

“…The PSS of GP-682 and GPA-696 were isolated and puri ed from a total saponin extract of Radix platycodonis [24]. The preparation process was based on our previously published paper [25]. The puri ed PSS was identi ed using HPLC and NMR methods.…”

“…The amphiphilic GP-682 was identi ed as a key PSS (shown in Fig. 1a left), which was reported to improve dosimetry of [ 18 F]-phillygenin in lung tissue [25]. The preparations of GP-682 micelles and GP-682/Nile Red micelles were performed using their selfaggregation capacity.…”

“…GP-682 and the platycodon secondary saponin 3-O-b-Dglucopyranosylplatyconic acid 696 (GPA-696) were the main metabolites [24]. GP-682 had better biological activity than GPA-696 in our previous study [25], which helped increase drug delivery to the lung tissue.…”

Micelles Self-Assembled by 3-O-β-D-Glucopyranosyl Latycodigenin Enhance Cell Membrane Permeability, Promote Antibiotic Pulmonary Targeting and Improve Anti-infective Efficacy

“…GP-682 and the platycodon secondary saponin 3-O-b-D-glucopyranosylplatyconic acid 696 (GPA-696) were the main metabolites [24]. GP-682 had better biological activity than GPA-696 in our previous study [25], which helped increase drug delivery to the lung tissue.…”