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Platycodon grandiflorus root extract (PGE) has shown various properties, such as anti-hyperlipidemia, anti-diabetic, and anti-obesity, but mostly in animal studies. Therefore, we conducted a preliminary study on the anti-obesity effect of PGE in 108 Korean adults (aged 20–60 years, 30 kg/m2 ≥ body mass index ≥ 23 kg/m2). The participants were randomly assigned to four groups and were administered the placebo, PGE571 (571 mg as PGE), PGE1142 (1142 mg as PGE), and PGE2855 (2855 mg as PGE), independently, for 12 weeks. Body composition, nutrient intake, computed tomography scan, and plasma adipokines, as well as hepatic/renal function markers, were assessed. The PGE571 group revealed a significant decrease in body fat mass and body fat percentage when compared with the placebo group. Moreover, the total abdominal and subcutaneous fat areas were significantly decreased following PGE (PGE2855 group) supplementation. These results provide useful information on the anti-obesity effect of PGE for overweight and obese adult humans.

Background Anthracyclines, alone or in combination with other drugs, are among the most effective chemotherapeutic agents to treat breast cancer both in the adjuvant and neoadjuvant setting. Unfortunately, anthracycline-associated dose-dependent cardiotoxicity is a limiting factor in clinical use. Extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity. However, most cardioprotective agents have shown little effect in clinical trials. Herbal medicines are pure, natural substances that have been used for centuries in many countries, including China. This trial aims to evaluate the cardioprotective effects and safety of Platycodon grandiflorum granules compared to placebo granules in patients with early breast cancer receiving anthracycline-based chemotherapy. Method/design This study is a single-center, double-blinded, randomized, placebo-controlled, parallel-group trial. A total of 120 patients will be randomly allocated in a 1:1 ratio to receive either P. grandiflorum granules or placebo granules twice daily for 12 weeks. The primary outcome is heart failure (either clinical or subclinical). The secondary outcomes include all-cause mortality, cardiac death, electrocardiogram (ECG) findings, left ventricular diastolic function, longitudinal systolic strain and velocities measured by tissue Doppler imaging, cardiac biomarkers, such as troponin I (TnI), brain natriuretic peptide (BNP), and creatine kinase isoenzymes (CK-MB). Assessments will be performed at baseline (before randomization) and 3, 6, 9, 12, 16, and 20 weeks after randomization. Discussion This will be the first clinical trial to evaluate the cardioprotective effects and safety of P. grandiflorum in patients with early breast cancer receiving anthracycline-based chemotherapy. We are also performing this trial to assess the feasibility of a larger-scale clinical trial in the future. Trail registration Chinese Clinical Trial Registry, ChiCTR-IPR-16009256 . Registered on 23 September 2016.

An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection routes via lysosome- and transmembrane protease serine 2 (TMPRSS2)-driven entry. Mechanistically, PD prevents host entry of SARS-CoV-2 by redistributing membrane cholesterol to prevent membrane fusion, which can be reinstated by treatment with a PD-encapsulating agent. Furthermore, the inhibitory effects of PD are recapitulated by the pharmacological inhibition or gene silencing of NPC1 , which is mutated in patients with Niemann–Pick type C (NPC) displaying disrupted membrane cholesterol distribution. Finally, readily available local foods or herbal medicines containing PG root show similar inhibitory effects against SARS-CoV-2 infection. Our study proposes that PD is a potent natural product for preventing or treating COVID-19 and that briefly disrupting the distribution of membrane cholesterol is a potential novel therapeutic strategy for SARS-CoV-2 infection. COVID-19: Closing the cellular door on coronavirus A molecule derived from a traditional Korean herbal medicine can impede entry of SARS-CoV-2 into cultured cells. The coronavirus responsible for COVID-19 can enter the cell via direct fusion with the plasma membrane, or after internalization into organelles called lysosomes. South Korean researchers led by Seungtaek Kim of the Institut Pasteur Korea, Seongnam, and C. Justin Lee at the Institute for Basic Science, Daejon, have identified a compound that can thwart both modes of entry. They treated cultured human cells with platycodin D (PD), extracted from a plant used throughout East Asia as a remedy for respiratory disease. The researchers showed that PD inhibits SARS-CoV-2 fusion with the plasma membrane while also blocking lysosomal release. This mechanism appears to be mediated by PD’s influence on membrane cholesterol content, suggesting a novel strategy for treating COVID-19.

Platycodonis radix is extensively used for treating cough, excessive phlegm, sore throat, bronchitis and asthma in the clinic. Meanwhile, the stems, leaves and seeds of Platycodon grandiflorum (PG) have some pharmaceutical activities such as anti-inflammation and anti-oxidation effects, etc. These effects must be caused by the different metabolites in various parts of herb. In order to profile the different parts of PG, the ultra-high performance liquid chromatography combined with quadrupole time-of- flight mass spectrometry (UPLC-QTOF-MSE) coupled with UNIFI platform and multivariate statistical analyses was used in this study. Consequently, for the constituent screening, 73, 42, 35, 44 compounds were characterized from the root, stem, leaf and seed, respectively. The stem, leaf and seed contain more flavonoids but few saponins that can be easily discriminated in the root. For the metabolomic analysis, 15, 5, 7, 11 robust biomarkers enabling the differentiation among root, stem, leaf and seed, were discovered. These biomarkers can be used for rapid identification of four different parts of PG grown in northeast China.

The bluish-purple petals of Chinese bellflower, Platycodon grandiflorum (kikyo in Japanese), contain platyconin (1) as the major anthocyanin. Platyconin (1) is a polyacylated anthocyanin with two caffeoyl residues at the 7-position, and its color is stable in a diluted, weakly acidic aqueous solutions. HPLC analysis of the fresh petal extract showed the presence of several minor pigments. Photo-diode array detection of minor pigments suggested that some of these were polyacylated anthocyanins. To establish the relationship between structure and stability of the acylated anthocyanins and to obtain information on their biosynthetic pathways, minor pigments were isolated from the petals, and their structures were determined by MS and NMR analyses. Four known (2–5) and three new anthocyanins (6–8) were identified, which contained a delphinidin chromophore, and four of these (5–8) were diacylated anthocyanins, in which the acyl-glucosyl-acyl-glucosyl chain was attached at the 7-O-position of the delphinidin chromophore. These diacylated anthocyanins exhibited a bluish-purple color at pH 6, which was stable for more than a week.

Platycodon grandiflorum belongs to the Campanulaceae family and is an important medicinal and food plant in East Asia. However, on the whole, the genome evolution of P. grandiflorum and the molecular basis of its major biochemical pathways are poorly understood. We reported a chromosome-scale genome assembly of P. grandiflorum based on a hybrid method using Oxford Nanopore Technologies, Illumina sequences, and high-throughput chromosome conformation capture (Hi-C) analysis. The assembled genome was finalized as 574 Mb, containing 41,355 protein-coding genes, and the genome completeness was assessed as 97.6% using a Benchmarking Universal Single-Copy Orthologs analysis. The P. grandiflorum genome comprises nine pseudo-chromosomes with 56.9% repeat sequences, and the transcriptome analysis revealed an expansion of the 14 beta-amylin genes related to triterpenoid saponin biosynthesis. Our findings provide an understanding of P. grandiflorum genome evolution and enable genomic-assisted breeding for the mass production of important components such as triterpenoid saponins.

Six lignols (1–6), including two new compounds (+)-(7R,8R)-palmitoyl alatusol D (1) and (+)-(7R,8R)-linoleyl alatusol D (2), along with four phenolics (7–10), a neolignan (11), three alkyl aryl ether-type lignans (12–14), two furofuran-type lignans (15–16), three benzofuran-type lignans (17–19), a tetrahydrofuran-type lignan (20), and a dibenzylbutane-type lignan (21) were isolated from the ethyl acetate-soluble fraction of the methanol extract of Platycodon grandiflorum (Jacq.) A. DC. root. The chemical structures of the obtained compounds were elucidated via high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy analyses. The obtained spectroscopic data agreed well with literature. Among the isolated compounds, eighteen (1–7 and 11–21) were isolated from P. grandiflorum and the Campanulaceae family for the first time. This is the first report on lignol and lignan components of P. grandiflorum. The anti-inflammatory effects of the isolated compounds were examined in terms of their ability to inhibit the production of pro-inflammatory cytokines IL-6, IL-12 p40, and TNF-α in lipopolysaccharide-stimulated murine RAW264.7 macrophage cells. Nine compounds (4–6, 12, and 15–19) exhibited inhibitory effects on IL-12 p40 production, eleven compounds (1–6, 12, 15–17, and 19) exhibited inhibitory activity on IL-6 production, and eleven compounds (1–6 and 15–19) exhibited inhibitory effects against TNF-α. These results warrant further investigation into the potential anti-inflammatory activity and general benefits of the phenolic constituents of P. grandiflorum root.

Platycodon grandiflorum (PG) is known as a high-potential material in terms of its biological activity. The objective of this report is to provide chromatographic and mass fragment ion data of 38 simultaneously identified saponins, including novel compounds, by analyzing them through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QToF/MS). In so doing, we investigated their diverse conditions, including morphological parts (stems, roots, buds, and leaves), peeling (or not), and blanching of PG. The total contents of individual saponins indicated an order of roots (containing peel, 1674.60 mg/100 g, dry weight) > buds (1364.05) > roots (without peel, 1058.83) ≈ blanched roots (without peel, 945.17) ≈ stems (993.71) ≈ leaves (881.16). When considering three types of aglycone, the platycodigenin group (55.04 ~ 68.34%) accounted for the largest proportion of the total content, whereas the platycogenic acid A group accounted for 17.83 ~ 22.61%, and the polygalacic acid group represented 12.06 ~ 22.35%. As they are classified as major compounds, novel saponins might be utilized for their role in healthy food for human consumption. Additionally, during blanching, the core temperature of PG was satisfied with the optimal condition, thus activating the enzymes related to biotransformation. Furthermore, through the use of this comprehensive data, additional studies related to buds, as well as roots or the characterization of individual saponins, can be conducted in a rapid and achievable manner.

The study is aimed at investigating the immunoenhancement activity of polysaccharides from Platycodon grandiflorum polysaccharides (PGPSs) in vitro. In this study, some research on lymphocyte proliferation, cell cycle, and the levels of CD4+ and CD8+ T cells were performed. Four different concentrations of PGPSs (PGPStc, PGPS60c, PGPS80c, and PGPStp) were harvested and added to peripheral blood T lymphocytes. We observed significant increases in T lymphocyte proliferation at PGPStc groups individually or synergistically with phytohemagglutinin (PHA) at most concentrations, and their lymphocyte proliferation rates were the highest. The active sites of PGPStc and PGPS60c were subsequently chosen. Then, we utilized flow cytometry to determine lymphocyte cell cycle distribution and levels of CD4+ and CD8+ T cells. At most time points, PGPStc could facilitate lymphocyte cell cycle progression from the G0/G1 phase to the S and G2/M phases and, simultaneously, increase the levels of CD4+ and CD8+ T cells. These results indicate that PGPStc enhances the immune functions, suggesting that PGPStc could be a potential immunopotentiator for further in vivo and clinical trial experiments.

Background Acute lung injury (ALI) is a severe respiratory disease accompanied by diffuse inflammatory responses induced by various clinical causes. Many fresh medicinal plants have shown better efficacy than their dried forms in preventing and treating diseases like inflammation. As a classical Chinese herb, platycodon grandiflorum (PG) has been demonstrated effective in treating pneumonia, but most of previous studies focused on the efficacy of processed or dried PG formats, while the specific benefits of its fresh form are still underexplored. Exosome-like nanoparticles derived from medicinal plants are expected to point out an important direction for exploring the material basis and mechanism of this fresh herbal medicine. Results The fresh form of PG could effectively improve ALI induced by lipopolysaccharide (LPS), relieve lung histopathological injury and weight loss, and reduce levels of inflammatory factors in mice, exhibiting better efficacy than dried PG in the treatment of ALI. Further extraction and purification of PG exosome-like nanoparticles (PGLNs) demonstrated that PGLNs had good biocompatibility, with characteristics consistent with general exosome-like nanoparticles. Besides, proteomic analysis indicated that PGLNs were rich in a variety of proteins. Animal experiments showed that PGLNs improved the pathological changes in LPS-induced lung tissues, inhibited the expression of inflammatory factors and promoted the expression of anti-inflammatory factors, and exerted a regulatory effect on the polarization of lung macrophages. Cell experiments further confirmed that PGLNs could be effectively taken up by RAW264.7 cells and repolarize M1 macrophages into M2 type, therefore reducing the secretion of harmful cytokines. Moreover, non-targeted metabolomics analysis reveals that PGLNs reduce inflammation and control macrophage polarization in a manner closely linked to pathways including glycolysis and lipid metabolism, highlighting a potential mechanism by which PGLNs protect the lungs from inflammatory damage like ALI. Conclusion Fresh PG has better anti-inflammatory and repair effects than its dried form. As one of the most effective active substances in fresh PG, PGLNs may regulate macrophage inflammation and polarization by regulating metabolic pathways including lipid metabolism and glycolysis, so as to reduce inflammation and repair lung injury. Graphical Abstract