Characterization of Saponins from Various Parts of Platycodon grandiflorum Using UPLC-QToF/MS

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.

Crude Saponin from Platycodon grandiflorum Attenuates Aβ-Induced Neurotoxicity via Antioxidant, Anti-Inflammatory and Anti-Apoptotic Signaling Pathways

(1) Background: Although Platycodon grandiflorum saponins exhibit many beneficial biological effects in various diseases and conditions, how they protect nerve cells against neurodegenerative diseases and Alzheimer’s disease (AD) pathology is unknown. We investigated whether P. grandiflorum crude saponin (PGS) protects neurons from neurodegeneration caused by amyloid beta (Aβ)-induced oxidative stress. (2) Methods: Hippocampal neuron HT-22 cells were used in the in vitro experiment, and AD mice (5XFAD mice) were used as the in vivo model. Intracellular reactive oxygen species (ROS) was stained with DCF-DA and assessed using fluorescence microscopy. To elucidate the mechanism underlying neuroprotection, intracellular protein levels were assessed by western blotting. In 5XFAD mice, an animal model of AD, nerve damage recovery due to the induction of Aβ toxicity was evaluated by histological analysis. (3) Results: PGS attenuates Aβ-induced neurotoxicity by inhibiting Aβ-induced reactive oxygen species (ROS) production and apoptosis in HT-22 cells. Furthermore, PGS upregulated Nrf2-mediated antioxidant signaling and downregulated NF-κB-mediated inflammatory signaling. Additionally, PGS inhibited apoptosis by regulating the expression of apoptosis-associated proteins. In addition, PGS ameliorated Aβ-mediated pathologies, leading to AD-associated cognitive decline. (4) Conclusions: Taken together, these findings suggest that PGS inhibits Aβ accumulation in the subiculum and cerebral cortex and attenuates Aβ toxicity-induced nerve damage in vitro and in vivo. Therefore, PGS is a resource for developing AD therapeutics.

Effects of Platycodon grandiflorum on Gut Microbiome and Immune System of Immunosuppressed Mouse

Platycodon grandiflorum (PG) is a perennial plant that has been used as a traditional remedy to control immune-related diseases. PG was steamed and dried to improve its taste (PGS). The aim of the study was to investigate the effects of PG and PGS (PG-diets) on the gut microbiome and immune system. We treated PG-diets to immunosuppressed mice via cyclophosphamide (CPA) injection. After two weeks of the supplement, we evaluated specific genera related to body weight and serum immunoglobulin levels and analyzed 16S rRNA sequencing and metagenomics statistical analysis. PG-diets groups showed an increased abundance of microorganisms in immunodeficient mice compared to the control group (NC). Moreover, Akkermansia significantly decreased in response to the CPA in the NC group at the genus level, whereas its abundance increased in the PG-diets groups. We also found that the modulation of the gut microbiome by PG-diets was correlated with body weight, IgA, and IgM levels. The results demonstrate that PG-diets may improve the health benefits of immunosuppressed mice by altering the gut microbiome, though not much difference was found between PG and PGS treatments. Finally, this is the first study showing the effects of PGS-diets on the gut microbiome and immune system as a potential nourishing immunity supplement.

Lung-targeted Macrophage Biomimetic Nanocarriers Based on Platycodon Grandiflorum Polysaccharides for Calming Cytokine Storm in Pneumonia

Background Pneumonia is a life-threatening respiratory disease without effective treatment due to uncontrolled inflammation of the lung tissue. Suppression of cytokine storms may be one of the keys to saving the lives of patients with severe pneumonia. Given the fragile delivery efficiency of drugs in vivo, novel delivery platforms to address these issues are necessary. Results Here, we developed a biomimetic nanocarrier (MNPs) with macrophage membranes coated ROS-responsive Platycodon grandiflorum polysaccharides nanoparticles (PNPs) for targeted delivery of curcumin (MNPs@Cur) to inflamed lungs and treat inflammation by calming cytokine storms. In the study, we could clearly find that MNPs@Cur significantly attenuated inflammation and cytokine storm syndrome in acute lung injury (ALI) mice by neutralizing multiple proinfammatory cytokines. Interestingly, we found that the PNPs also had potent pulmonary targeting compared to other polysaccharide carriers, which probably means that PNPs have inherited the natural targeting ability in the medicinal guide theory of Traditional Chinese Medicine (TCM). Conclusion The results demonstrated that the developed drug delivery system may serve as an effective and safe nanoplatform for the treatment of pneumonia, as well as provide experimental scientific basis for the medicinal guide theory of TCM and its clinical application.

Bionanosystem Based on Platycodon Grandifloras “Guides the Medicine Upward” for Targeting Lung Inflammation to Calm the Cytokine Storm

Pneumonia can lead to high morbidity and mortality due to uncontrolled inflammation of the lung tissue. More and more evidences indicate that cytokine storms play a vital role in the progression of inflammatory lung diseases. Blocking cytokine storms may be one of the keys to saving the life of patients with severe pneumonia. According to the guide theory of Traditional Chinese Medicine (TCM) and the inherent affinity of macrophages for the site of inflammation, we constructed a bionic drug delivery system (MPNPs) derived from macrophage-membrane (MM) encapsulated ROS-responsive Platycodon grandiflorum polysaccharide (PGP) nanoparticles (PNPs) to calm down the cytokine storm and improve lung inflammation. By loading the anti-inflammatory agent Curcumin (Cur), we could clearly find that MPNPs@Cur were better targeted to the inflammatory cell and more significantly suppressed the release of proinflammatory factors such as IL-6 and TNF-α. In acute lung injury (ALI) mice treated with MPNPs@Cur significantly reduced inflammation and cytokine storm syndrome, while also alleviating symptoms in mice with ALI. Interestingly, we found that the PNPs also had potent pulmonary targeting compared to other polysaccharide carriers, which is in line with the guide theory of the attribution of the Platycodon grandiflorum to the lung. Additionally, MM segregate pro-inflammatory cytokines to suppress local inflammation. The synergistic effect of drug therapy and the separation of inflammatory cytokines from this biomimetic drug delivery system leads to an increase in the therapeutic effect of ALI. Rational design of drug delivery platform to improve the treatment of lung injury is revealed in our study, which inherits and develops the important theories of TCM through the perfect combination of guide theory and modern biomimetic nanotechnology, as well as provides experimental scientific basis for the clinical application of channel ushering drugs.

New insights of low-temperature plasma effects on seeds germination of Platycodon grandiflorum

Low temperature plasma (LTP) exerted beneficial effects on seed germination and crop growth. With application of LTP on seed germination of Platycodon grandiflorum, germination indexes and physiological parameters and transcriptome profile were investigated in this experiment. The results showed the seed germination rate and germinating potential of Platycodon grandiflorum in LTP increased by 24.7% and 30.7% comparing to CK respectively (p < 0.05). The SOD and CAT activity of the seed sprouts increased by 26.78% and 12.41% comparing to CK. Transcriptome results showed that 14342 up-regulated and 4366 down-regulated different expressing genes (DEGs) at LTP and CK. A considerable number of DEGs related to the plant hormone signal transduction, peroxisome, oxidative phosphorylation, starch and surose in response to low temperature plasma were identified in this study. The transcriptomic gene expression profiles present a valuable genomic tool to the molecular mechanisms of Platycodon grandiflorum seed germination underlying low temperature plasma. which can provide theoretical basis and practical guidance for cultivation and planting of Platycodon grandiflorum.

Phenolic Constituents from Platycodon grandiflorum Root and Their Anti-Inflammatory Activity

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.