Platycodi radix aqueous extract salvages doxorubicin-induced senescence by mitochondrial reactive oxygen species reduction in umbilical cord matrix stem cells.

Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, derived from Wharton's jelly of the human umbilical cord, has emerged as a promising approach for treating degenerative diseases. Nevertheless, growing evidence indicates that the function of stem cells declines with age, thereby limiting their regenerative capacity. The primary objective in this study is to investigate the beneficial effects of P. radix in senescent stem cells. We conducted experiments to showcase that diminished levels of Lamin B1 and Sox-2, along with an elevation in p21, which serve as indicative markers for the senescent stem cells. Our findings revealed the loss of Lamin B1 and Sox-2, coupled with an increase in p21, in umbilical cord stromal stem cells subjected to a low-dose (0.1 µM) doxorubicin (Dox) stimulation. However, P. radix restored the Dox-damage in the umbilical cord stromal stem cells. P. radix reversed the senescent conditions when the umbilical cord stromal stem cells exposed to Dox-induced reactive oxygen species (ROS) and mitochondrial membrane potential are significantly changed. In Dox-challenged aged umbilical cord stromal stem cells, P. radix reduced senescence, increased longevity, prevented mitochondrial dysfunction and ROS and protected against senescence-associated apoptosis. This study suggests that P. radix might be as a therapeutic and rescue agent for the aging effect in stem cells. Inhibition of cell death, mitochondrial dysfunction and aging-associated ROS with P. radix provides additional insights into the underlying molecular mechanisms.

Screening of Platycodonis Radix Fractions for Antiobesity Activities and Elucidation of Its Molecular Mechanisms in High-Fat Diet-Fed C57BL/6 Mice.

Obesity is a threat to public health and effective new medications are required. Platycodonis Radix (PR) is a traditional medicinal/dietary plant with activities against obesity. Using mice given a diet rich in fat, the antiobesity components of PR were identified and their molecular mechanisms were clarified further in this investigation. Initially, the impacts of PR fractions on liver histology and biochemical markers were assessed. Subsequently, the degrees of lipogenic and lipolytic gene and protein expressions were determined. Oral administration of PR polysaccharides (PG) (0.80 g/kg body weight) improved liver function (alanine aminotransferase and aspartate aminotransferase) and its antioxidant activities (total superoxide dismutase, glutathione peroxidase, and malondialdehyde), as well as alleviated blood lipid (total cholesterol, total triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) values, inflammatory systemic (TNF-α and IL-1ß), and histological abnormalities within the liver. Furthermore, PG administration downregulated the expression for lipogenic genes (ACC and FAS) and upregulated the expression for the lipolytic gene (PPARα, LPL, CPT1, and HSL). Importantly, PG raised AMPK phosphorylation and decreased SREBP-1c protein synthesis. Thus, it is possible that PG stimulates the AMPK-LPL/HSL path (lipolytic route) plus the AMPK-ACC/PPARα-CPT1 path (associated to ß-oxidation of fatty acids), while inhibiting the AMPK/(SREBP-1c)-ACC/FAS path (lipogenic route). In summary, PG has the ability to regulate lipid metabolism, and it may be useful to pharmacologically activate AMPK with PG to prevent and cure obesity.

Recent advances in Platycodon grandiflorum polysaccharides: Preparation techniques, structural features, and bioactivities.

Platycodon grandiflorum, a globally recognized medicinal and edible plant, possesses significant nutritional value and pharmacological value. In traditional Chinese medicine, it has the effects of tonifying the spleen and replenishing the Qi, moistening the lung and relieving the cough, clearing the heat and detoxifying, and relieving the pain. Accumulating evidence has revealed that the polysaccharides from P. grandiflorum (PGPs) are one of the major and representative biologically active macromolecules and have diverse biological activities, such as immunomodulatory activity, anti-inflammatory activity, anti-tumor activity, regulation of the gut microbiota, anti-oxidant activity, anti-apoptosis activity, anti-angiogenesis activity, hypoglycemic activity, anti-microbial activity, and so on. Although the polysaccharides extracted from P. grandiflorum have been extensively studied for the extraction and purification methods, structural characteristics, and pharmacological activities, the knowledge of their structures and bioactivity relationship, toxicologic effects, and pharmacokinetic profile is limited. The main purpose of the present review is to provide comprehensively and systematically reorganized information on extraction and purification, structure characterizations, and biological functions as well as toxicities of PGPs to support their therapeutic potentials and sanitarian functions. New valuable insights for future research regarding PGPs were also proposed in the fields of therapeutic agents and functional foods.

Preparation methods, structural characteristics, and biological activity of polysaccharides from Platycodon grandiflorus.

Platycodon grandiflorus (P. grandiflorus), a traditional Chinese medicinal herb used for both medicine and food, has a long history of treating respiratory infections, bronchitis, pneumonia, and other lung-related diseases. The therapeutic effects of P. grandiflorus are attributed to its chemical components, including polysaccharides. Among these components, Platycodon grandiflorus polysaccharides (PGP) are recognized as one of the most important and abundant active ingredients, exhibiting various biological activities such as prebiotic, antioxidant, antiviral, anticancer, antiangiogenic, and immune regulatory properties. Incorporating the principles of traditional Chinese medicine, carrier concepts, and modern targeted drug delivery technologies, PGP can influence the target sites and therapeutic effects of other drugs while also serving as a drug carrier for targeted and precise treatments. Therefore, it is essential to provide a comprehensive review of the extraction, separation, purification, physicochemical properties, and biological activities of PGP. In the future, by integrating new concepts, technologies, and processes, further references and guidance can be provided for the comprehensive development of PGP. This will contribute to the advancement of P. grandiflorus in various fields such as pharmaceuticals, health products, and food.

Revealing the "Yin-Jing" mystery veil of Platycodon grandiflorum by potentiating therapeutic effects and lung-oriented guidance property.

ETHNIC PHARMACOLOGICAL RELEVANCE: "Yin-Jing" medicine (YJM) has been widely used by both ancient and modern Chinese medicine practitioners during long-term clinical practice. However, it remains unclear how to best guide other medicines to the targeted organs in a traditional Chinese medicine (TCM) prescription. Here, in an attempt to explain the scientific connotation of the YJM property (YJMP) attributed to a basic TCM theory, Platycodon grandiflorum (PG) was chosen as a case study to reveal the mystery of YJMP theory. AIM OF THE STUDY: The main purpose of this study is to employ modern chemical and molecular biology methods to confirm the "Yin-Jing" effect of PG, and further clarify its material basis and related possible mechanism. MATERIALS AND METHODS: The ammonia-induced lung injury rat model was utilized to determine the optimal dosage of traditional prescription Hui Yan Zhu Yu decoction (HYZYD) using Wright Giemsa staining, HE staining, Masson staining, and TUNEL analysis. With the same way, PG was confirmed to have potentiating therapeutic effect (PTE) by comparison with HYZYD and [HYZYD-PG]. TMT proteomics was used to reveal the "Yin-Jing" mechanism of action. Western blot assay (WB) was employed for verification of differentially expressed proteins. Additionally, four non-crossing fragmentations (Fr. A-D) were characterized by RPLC/SEC-ELSD and HILIC-ESI--Q-OT-IT-MS techniques. The PTE and guidance property assays were utilized to evaluate "Yin-Jing" functions by a compatible combination of hydroxysafflor yellow A (HYA) using qPCR, FCM, WB, HPLC, high content cell imaging (HCI) and high-resolution live-cell imaging (HRLCI) techniques. RESULTS: The HYZYD-M (medium dose group) significantly improved the lung injury level in a pneumonia model of rats. PG enhanced the therapeutic effect of HYZYD ascribed to Yin-Jing PTE functions. TMT proteomics revealed a category of differentially expressed proteins ascribed to Golgi-ER between HYZYD and [HYZYD-PG]. Fr. C (i.e., saponins) and Fr. D (i.e., lipids) were determined as therapeutic fragmentations via the LPS-induced A549 cell injury model; however, Fr. B (fructooligosaccharides and small Mw fructans) had no therapeutic effect. Further compatibility PTE assays confirmed Fr. B significantly improved efficiency by a combination of HYA. The guidance assays showed Fr. B could significantly increase the uptake and distribution of HYA into lung cells and tissues. HCI assays showed that Fr. B increased uptake of HYA accompanied by significant activation of Golgi-ER. Unlike Fr. B, HRLCI showed that Fr. A, C and D were not only unobvious activations of Golgi-ER but also insignificant facilitation of colocalizations between HYA and Golgi-ER. CONCLUSIONS: Fr. B is believed to be a key YJMP material basis of PG attributed to Yin-Jing PTE with characteristic of lung-oriented guidance property, whereas another abound Fr. C was determined to have synergistic effects rather than Yin-Jing material basis.

Identification and functional characterization of two trans-isopentenyl diphosphate synthases and one squalene synthase involved in triterpenoid biosynthesis in Platycodon grandiflorus.

MAIN CONCLUSION: Two trans-isopentenyl diphosphate synthase and one squalene synthase genes were identified and proved to be involved in the triterpenoid biosynthesis in Platycodon grandiflorus. Platycodon grandiflorus is a commonly used traditional Chinese medicine. The main bioactive compounds of P. grandiflorus are triterpenoid saponins. The biosynthetic pathway of triterpenoid saponins in P. grandiflorus has been preliminarily explored. However, limited functional information on related genes has been reported. A total of three trans-isopentenyl diphosphate synthases (trans-IDSs) genes (PgFPPS, PgGGPPS1 and PgGGPPS2) and one squalene synthase (SQS) gene (PgSQS) in P. grandiflorus were screened and identified from transcriptome dataset. Subcellular localization of the proteins was defined based on the analysis of GFP-tagged. The activity of genes was verified in Escherichia coli, demonstrating that recombinant PgFPPS catalysed the production of farnesyl diphosphate. PgGGPPS1 produced geranylgeranyl diphosphate, whereas PgGGPPS2 did not exhibit catalytic activity. By structural identification of encoding genes, a transmembrane region was found at the C-terminus of the PgSQS gene, which produced an insoluble protein when expressed in E. coli but showed no apparent effect on the enzyme function. Furthermore, some triterpenoid saponin synthesis-related genes were discovered by combining the component content and the gene expression assays at the five growth stages of P. grandiflorus seedlings. The accumulation of active components in P. grandiflorus was closely associated with the expression level of genes related to the synthesis pathway.

Polysaccharides from Platycodon grandiflorus attenuates high-fat diet induced obesity in mice through targeting gut microbiota.

The root of Platycodon grandiflorus (PG), abundant in soluble polysaccharides, has a long history in traditional Asian diets and herbal medicine due to its anti-inflammatory activity and anti-obesity effects. Our previous study was the first to establish a link between the beneficial effects of PG and changes in the gut microbiota, and suggested potential roles that the polysaccharide components play. However, more evidence was needed to understand the anti-obesity functions of polysaccharides from PG (PS) and their relationship with the regulation of the gut microbiota. In this study, we first performed an experiment to explore the anti-obesity activities of PS: Male C57BL/6 mice (six-weeks-old) were fed either a standard control diet (CON), or a high-fat diet (HFD) to induce obesity, or a HFD supplemented with PS (HFPS) for 8 weeks. Body weight and food intake were monitored throughout. Lipid metabolism were determined and related gene expression changes in adipose tissues were analyzed by RNA-seq. Amplicon sequencing of the bacterial 16 S rRNA gene was used to explore gut microbiota structure in fecal samples. Then, we performed the second experiment to explore whether the anti-obesity activities of PS were dependent on the regulation of the gut microbiota: Male C57BL/6 mice (six-weeks-old), treated with an antibiotic cocktail to reduce the gut microbial load, were fed either a HFD (A-HFD) or a HFPS (A-HFPS) diet for 8 weeks. Finally, we used in vitro fermentation experiments to verify the effects of PS on the growth and metabolic activities of the gut microbes. We found that PS significantly reduced HFD-induced weight gain and excessive fat accumulation, changed the expression of key genes involved in lipid metabolism, and attenuated HFD-induced changes in the gut microbiota. However, PS did not affect fat accumulation or lipid metabolism in the gut microbiota depleted mice. Overall, our results show that PS has significant effects on the gut microbiota in the mouse model, and the anti-obesity effects of PS are mediated via changes in the gut microbiota composition and metabolic activity.

Histone Deacetylase Inhibitor, Sodium Butyrate-Induced Metabolic Modulation in Platycodon grandiflorus Roots Enhances Anti-Melanogenic Properties.

While the status of histone acetylation is a critical regulator of chromatin's structure with a significant impact on plant physiology, our understanding of epigenetic regulation in the biosynthesis of active compounds in plants is limited. In this study, Platycodon grandiflorus was treated with sodium butyrate (NaB), a histone deacetylase inhibitor, to investigate the influence of histone acetylation on secondary metabolism. Its treatment with NaB increased the acetylation of histone H3 at lysine 9, 14, and 27 and enhanced the anti-melanogenic properties of P. grandiflorus roots. Through transcriptome and differentially expressed gene analyses, we found that NaB influenced the expression of genes that were involved in both primary and secondary metabolic pathways. In addition, NaB treatment caused the accumulation of polyphenolic compounds, including dihydroquercetin, gallic acid, and 2,4-dihydroxybenzoic acid. The NaB-induced transcriptional activation of genes in the phenylpropanoid biosynthetic pathway influenced the anti-melanogenic properties of P. grandiflorus roots. Overall, these findings suggest the potential of an epigenomic approach to enhance the medicinal qualities of medicinal plants.

Anti-inflammatory effect and metabolic mechanism of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on atopic dermatitis in vivo and in vitro.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune response. AD treatment include glucocorticoids and immunosuppressants. However, long-term treatment can have serious side effects. Thus, an effective AD treatment with fewer side effects is required. Natural materials, including herbal medicines, have potential applications. PURPOSE: This study evaluated the in vivo and in vitro therapeutic effects of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on AD and investigated the underlying metabolic mechanisms. METHODS: The anti-inflammatory effects of BS012 were assessed using a mouse model of AD induced by 1­chloro-2,4-dinitrobenzene (DNCB) and in tumor necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ) stimulated normal human epidermal keratinocytes (NHEKs). In DNCB-induced mice, total dermatitis score, histopathological analysis, and immune cell factors were assessed to evaluate the anti-atopic activity. In TNF-α/IFN-γ-stimulated NHEKs, pro-inflammatory cytokines, chemokines, and related signaling pathways were investigated. Serum and intracellular metabolomics were performed to identify the metabolic mechanism underlying the therapeutic effects of BS012 treatment. RESULTS: In DNCB-induced mice, BS012 showed potent anti-atopic activity, including reducing AD-like skin lesions and inhibiting the expression of Th2 cytokines and thymic stromal lymphopoietin. In TNF-α/IFN-γ-stimulated keratinocytes, BS012 dose-dependently inhibited the expression of pro-inflammatory cytokines and chemokines by blocking nuclear factor-kappa B and signal transducer and activator of transcription signaling pathways. Serum metabolic profiles of mice revealed significant changes in lipid metabolism related to inflammation in AD. Intracellular metabolome analysis revealed that BS012 treatment affected the metabolism associated with inflammation, skin barrier function, and lipid organization of the stratum corneum. CONCLUSION: BS012 exerts anti-atopic activity by reducing the Th2-specific inflammatory response and improving skin barrier function in AD in vivo and in vitro. These effects are mainly related to the inhibition of inflammation and recovery of metabolic imbalance in lipid organization. BS012, a novel combination with strong activity in suppressing the Th2-immune response, could be a potential alternative for AD treatment. Furthermore, the metabolic mechanism in vivo and in vitro using a metabolomics approach will provide crucial information for the development of natural products for AD treatment.

Extract of Platycodon grandiflorum Prevents Doxorubicin-induced Cardiotoxicity in Breast Cancer.

Doxorubicin (Dox) is a first-line chemotherapeutic agent applied in cancer treatment. Its long-term anticancer efficacy is restricted mainly due to its subsequent cardiotoxicity for patients. Platycodon grandiflorum (PG), an important traditional Chinese herb, has been reported to eliminate phlegm, relieve cough, and reduce inflammatory diseases. Previous clinical studies found that PG has cardioprotective effects for early breast cancer patients who received Dox-based chemotherapy. However, the cellular and molecular mechanisms underlying PG-mediated cardiotoxic rescue remain elusive. This study aimed to explore the protective role and potential molecular mechanisms of PG on Dox-induced cardiac dysfunction in a mouse model of breast cancer. PG significantly alleviated myocardial damage and prevented cardiomyocyte apoptosis induced by Dox. The expression levels of cytochrome C and cleaved caspase-3 significantly decreased, and the levels of Bcl-XL and B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein increased following PG treatment. Furthermore, PG remarkably enhanced the antimetastatic efficacy (versus the Dox group) by regulating the balance of matrix metalloproteinases/tissue inhibitors of metalloproteinases.

Ameliorative Effects of Flavonoids from Platycodon grandiflorus Aerial Parts on Alloxan-Induced Pancreatic Islet Damage in Zebrafish.

Platycodon grandiflorus (balloon flower), used as a food reserve as well as in traditional herbal medicine, is known for its multiple beneficial effects. In particular, this plant is widely used as a vegetable in Republic of Korea. We examined the ameliorative effects of P. grandiflorus on alloxan-induced pancreatic islet damage in zebrafish. The aerial part treatment led to a significant recovery in pancreatic islet size and glucose uptake. The efficacy of the aerial part was more potent than that of the root. Eight flavonoids (1-8) were isolated from the aerial part. Structures of two new flavone glycosides, designated dorajiside I (1) and II (2), were elucidated to be luteolin 7-O-α-L-rhamno-pyranosyl (1 → 2)-(6-O-acetyl)-ß-D-glucopyranoside and apigenin 7-O-α-L-rhamnopyranosyl (1 → 2)-(6-O-acetyl)-ß-D-glucopyranoside, respectively, by spectroscopic analysis. Compounds 1, 3, 4 and 6-8 yielded the recovery of injured pancreatic islets in zebrafish. Among them, compound 7 blocked KATP channels in pancreatic ß-cells. Furthermore, compounds 3, 4, 6 and 7 showed significant changes with respect to the mRNA expression of GCK, GCKR, GLIS3 and CDKN2B compared to alloxan-induced zebrafish. In conclusion, the aerial part of P. grandiflorus and its constituents conferred a regenerative effect on injured pancreatic islets.

Platycodon grandiflorus polysaccharide regulates colonic immunity through mesenteric lymphatic circulation to attenuate ulcerative colitis.

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms. The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice, increased colon length, and reduced DAI, spleen index, and pathological damage within the colon. PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity. Meanwhile, PGP restored the levels of Th1, Th2, Th17, and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity. Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation. Taken together, PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.

An evaluation of the qualitative superiority of the Mongolian medicinal herb hurdan-tsagaan (Platycodi Radix) from five different geographic origins based on anti-inflammatory effects.

ETHNOPHARMACOLOGICAL RELEVANCE: The contents and types of the active compounds in medicinal herbs depend greatly on their extraction methods, sources of origin and the modes of cultivation. Platycodon grandiflorus (Jacq.) A.DC. is an ethnic medicinal herb widely cultivated in China, and its dried root, Platycodi Radix (PR), is an important ingredient in herbal formulae for attenuating lung issues in Mongolian medical practice. However, research evaluating the superiority of PR based on harvesting regions is relatively limited. AIM: This study aimed to evaluate the qualitative superiority of PR from different regions based on anti-inflammatory effect. MATERIALS AND METHODS: A total of three commercial PR samples were obtained from Anguo, Bozhou and Shangluo, and two wild samples were obtained from Chifeng and Hinggan. PR extract (PRE) was prepared by water distillation, and platycodin D content in the extract was examined by HPLC-UVD. An optimal dose of PRE was administered to BALB/c mice with S. pneumoniae pneumonia, and IL-10 and TNF-α levels in lung tissue were examined by ELISA. HepG2 cells were treated with PRE, and an analysis of differentially expressed gene and functional enrichment was performed using an HTS2 assay. RESULTS: The contents of moisture, total ash, crude extract and platycodin D in the raw roots met the quality control requirements outlined in the Chinese Pharmacopoeia (2020 edition). The platycodin D content in the aqueous extract of the roots in descending order was 24.16% in PRE_Shangluo, 22.91% in PRE_Hinggan, 21.41% in PRE_Bozhou, 17.8% in PRE_Chifeng and 15.92% in PRE_Anguo. Furthermore, administration of PREs at an optimal dose of 2.0 g/kg resulted in some anti-inflammatory effect in mice with Streptococcus pneumoniae pneumonia, among which PRE_Shangluo administration exhibited a more obvious anti-inflammatory impact as shown by a significant decrease in the plasma white cell count (p < 0.05) and IL-10 level elevation and TNF-α reduction in lung tissue (p < 0.05) after treatment. In HepG2 cells treated with 100 µg/ml of each PRE, PRE_Hinggan and PRE_Shangluo resulted in significant differential expression of genes such as nuclear factor kappa B subunit 1 (NFKB1) and significant enrichment of pathways involved in the immune system, such as PI3K-Akt, MAPK and NF-kappa B signaling pathways. CONCLUSIONS: In this study, based on the anti-inflammatory effect, the quality of PR of Shangluo origin was superior to that of PR from the other four regions.

A Novel Drug with Potential to Treat Hyperbilirubinemia and Prevent Liver Damage Induced by Hyperbilirubinemia: Carbon Dots Derived from Platycodon grandiflorum.

Platycodon grandiflorum (PG) is a traditional Chinese medicine with a long history, but its active compounds have not been reported. In this study, novel carbon dots (CDs), PG-based CDs (PGC-CDs), were discovered and prepared from PG via calcinations and characterized by transmission electron microscopy; high-resolution transmission electron microscopy; X-ray diffraction, fluorescence, ultraviolet-visible, and Fourier-transform infrared spectrometers; X-ray photoelectron spectroscopy; and high-performance liquid chromatography. In addition, the safety and antioxidant activity of PGC-CDs was evaluated by RAW264.7 cells and LO2 cells. The therapeutic effects of PGC-CDs on hyperbilirubinemia and liver protection were evaluated in a bilirubin-induced hyperbilirubinemia mice model. The experiment confirmed that the diameter range of PGC-CDs was from 1.2 to 3.6 nm. PGC-CDs had no toxicity to RAW264.7 cells and LO2 cells at a concentration of 3.91 to 1000 µg/mL and could reduce the oxidative damage of cells caused by H2O2. PGC-CDs could inhibit the increase levels of bilirubin and inflammation factors and increase the levels of antioxidants and survival rate, demonstrating that PGC-CDs possessed anti-inflammatory and anti-oxidation activity. PGC-CDs may reduce the content of bilirubin, so as to reduce a series of pathological lesions caused by bilirubin, which has potential in treating hyperbilirubinemia and preventing liver damage induced by hyperbilirubinemia.

Platycodon grandiflorus root extract activates hepatic PI3K/PIP3/Akt insulin signaling by enriching gut Akkermansia muciniphila in high fat diet fed mice.

BACKGROUND: Increasing hepatic insulin signaling is found to be an important mechanism of Platycodon grandiflorus root to alleviate metabolic syndrome (MetS) symptoms such as insulin resistance, obesity, hyperlipidemia and hepatic steatosis, but the details are not yet clear. Since the main constituents of Platycodon grandiflorus root were hard to be absorbed by gastrointestinal tract, getting opportunity to interact with gut microbiota, we speculate the gut microorganisms may mediate its effect. PURPOSE: Our work aimed to confirm the critical role of gut microbes in the intervention of Platycodon grandiflorus root extract (PRE) on MetS, and investigate the mechanism. METHODS: Biochemical analyses, glucose tolerance test and hepatic lipidomics analysis were used to evaluate the anti-MetS effect of PRE on high fat diet (HFD) fed mice. Perform 16S rDNA analysis, qPCR analysis and in vitro co-incubation experiment to study its effect on gut microbes, followed by fecal microbiota transplantation (FMT) experiment and antibiotics intervention experiment. Also, the effect of Akkermansia muciniphila treatment on HFD mice was investigated. RESULTS: PRE alleviated lipid accumulation and insulin resistance in HFD mice and remodeled the fecal microbiome. It also increased the gene expression of colonic tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced TNF-α induced hepatic JNK-dependent IRS-1 serine phosphorylation and the impairment of PI3K/PIP3/Akt insulin signaling pathway. A. muciniphila was one of the most significantly enriched microbes by PRE treatment, and its administration to HFD mice showed similar effects to PRE, repairing the gut barrier and activating hepatic PI3K/PIP3/Akt pathway. Finally, anti-MetS effect of PRE could be delivered to FMT recipients, and PRE could not further attenuate MetS in gut microbiota depleted mice. CONCLUSION: We demonstrated for the first time that PRE alleviated MetS in a gut microbiota dependent manner, and found activation of hepatic insulin signaling mediated by gut A. muciniphila was a potential mechanism of it.

Identification and expression analysis of YABBY family genes in Platycodon grandiflorus.

Platycodon grandiflorus set ornamental, edible, and medicinal plant with broad prospects for further application development. However, there are no reports on the YABBY transcription factor in P. grandiflorus. Identification and analysis of the YABBY gene family of P. grandiflorus using bioinformatics means. Six YABBY genes were identified and divided into five subgroups. Transcriptome data and qRT-PCR were used to analyze the expression patterns of YABBY. YABBY genes exhibited organ-specific patterns in expression in P grandiflorus. Upon salt stress and drought induction, P. grandiflorus presented different morphological and physiological changes with some dynamic changes. Under salt treatment, the YABBY gene family was down-regulated; PgYABBY5 was up-regulated in leaves at 24 h. In drought treatment, PgYABBY1, PgYABBY2, and PgYABBY3 were down-regulated to varying degrees, but PgYABBY3 was significantly up-regulated in the roots. PgYABBY5 was up-regulated gradually after being down-regulated. PgYABBY5 was significantly up-regulated in stem and leaf at 48 h. PgYABBY6 was down-regulated at first and then significantly up-regulated. The dynamic changes of salt stress and drought stress can be regarded as the responses of plants to resist damage. During the whole process of salt and drought stress treatment, the protein content of each tissue part of P grandiflorus changed continuously. At the same time, we found that the promoter region of the PgYABBY gene contains stress-resistant elements, and the regulatory role of YABBY transcription factor in the anti-stress mechanism of P grandiflorus remains to be studied. PgYABBY1, PgYABBY2, and PgYABBY5 may be involved in the regulation of saponins in P. grandiflorus. PgYABBY5 may be involved in the drought resistance mechanism in P. grandiflorus stems and leaves. This study may provide a theoretical basis for studying the regulation of terpenoids by the YABBY transcription factor and its resistance to abiotic stress.

Ligand fishing of monoamine oxidase B inhibitors from Platycodon grandiflorus (Jacq.) A.DC. roots by the enzyme functionalised magnetic nanoparticles.

INTRODUCTION: As a famous traditional Chinese medicine, roots of Platycodon grandiflorus (Jacq.) A.DC. have shown multiple effects against neurodegenerative diseases. To investigate the components against Parkinson's disease (PD), the roots of P. grandiflora were selected as the research subject. OBJECTIVE: Screening and identifying of monoamine oxidase B (MAO-B) inhibitors from the roots of P. grandiflorum via enzyme functionalised magnetic nanoparticles (MNPs)-based ligand fishing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. METHOD: MAO-B functionalised MNPs have been synthesised for screening MAO-B inhibitors from the roots of P. grandiflorum. The ligands were identified by HPLC-MS and nuclear magnetic resonance (NMR) analysis, and their anti-PD activity was evaluated via MAO-B inhibition assay and cell viability assay in vitro. RESULTS: Two MAO-B inhibitors were fished out and identified by HPLC-MS as protocatechuic aldehyde (1) and coumarin (2), with the half maximal inhibitory concentrations of 28.54 ± 0.39 and 25.39 ± 0.29 µM, respectively. Among them, 1 could also significantly increase the viability of 6-hydroxydopamine-damaged PC12 cells. CONCLUSION: The results are helpful to elucidate the anti-PD activity of the plant, and the ligand fishing method has shown good potential in discovery of MAO-B inhibitors.

Seasonal variation in the total saponin content of platycodon roots cultivated in Japan.

Roots of Platycodon grandiflorus A. De Candolle (Campanulaceae), with the bark removed, have been used as food and frequently employed as herbal medicines for inflammatory diseases such as tonsillitis, dermatitis, and cough. Platycodins are the bioactive saponin components of these crude medicines. Recently, P. grandiflorus have been cultivated in Japan and are harvested from October to December according to conventional practices. Seasonal fluctuations in the total saponin content of these roots were determined using LC/MS methods to recommend harvesting times when the saponin content is high. Platycodins A and C are monoacetylated forms of platycodin D; however, the acetyl form is unstable and deacetylates easily. Here, the contents of platycodin D, platycodin D2, and platyconic acid A were measured as the total saponin content using alkaline hydrolysis for monoacetylated platycodins D, D2, and platyconic acid A. The results demonstrated that the saponin content in the roots decreased in summer, increased in autumn, but decreased again in late autumn.

Integrated Metabolome and Lipidome Strategy to Reveal the Action Pattern of Paclobutrazol, a Plant Growth Retardant, in Varying the Chemical Constituents of Platycodon Root.

Platycodon root, a medicinal food homology species which has been used in Asian countries for hundreds of years, is now widely cultivated in China. Treatment with paclobutrazol, a typical plant growth retardant, has raised uncertainties regarding the quality of Platycodon root, which have been rarely investigated. In the present study, metabolomic and lipidomic differences were revealed by ultra-high performance liquid chromatography coupled to ion mobility-quadrupole time of flight mass spectrometry (UPLC-IM-QTOF-MS). A significant decrease of platycodigenin-type saponins was observed in the paclobutrazol-treated sample. Carrying out a comprehensive quantitative analysis, the contents of total saponins and saccharides were determined to illustrate the mode of action of paclobutrazol on Platycodon root. This study demonstrated an exemplary research model in explaining how the exogenous matter influences the chemical properties of medicinal plants, and therefore might provide insights into the reasonable application of plant growth regulators.

Platycodon grandiflorum (Jacq.) A. DC.: A review of phytochemistry, pharmacology, toxicology and traditional use.

BACKGROUND: The traditional Chinese medicine Platycodon grandiflorum (Jacq.) A. DC. (PG, balloon flower) has medicinal and culinary value. It consists of a variety of chemical components including triterpenoid saponins, polysaccharides, flavonoids, polyphenols, polyethylene glycols, volatile oils and mineral components, which have medicinal and edible value. PURPOSE: The ultimate goal of this review is to summarize the phytochemistry, pharmacological activities, safety and uses of PG in local and traditional medicine. METHODS: A comprehensive search of published literature up to March 2022 was conducted using the PubMed, China Knowledge Network and Web of Science databases to identify original research related to PG, its active ingredients and pharmacological activities. RESULTS: Triterpene saponins are the primary bioactive compounds of PG. To date, 76 triterpene saponin compounds have been isolated and identified from PG. In addition, there are other biological components, such as flavonoids, polyacetylene and phenolic acids. These extracts possess antitussive, immunostimulatory, anti-inflammatory, antioxidant, antitumor, antiobesity, antidepressant, and cardiovascular system activities. The mechanisms of expression of these pharmacological effects include inhibition of the expression of proteins such as MDM and p53, inhibition of the activation of enzymes, such as AKT, the secretion of inflammatory factors, such as IFN-γ, TNF-α, IL-2 and IL-1ß, and activation of the AMPK pathway. CONCLUSION: This review summarizes the chemical composition, pharmacological activities, molecular mechanism, toxicity and uses of PG in local and traditional medicine over the last 12 years. PG contains a wide range of chemical components, among which triterpene saponins, especially platycoside D (PD), play a strong role in pharmacological activity, representing a natural phytomedicine with low toxicity that has applications in food, animal feed and cosmetics. Therefore, PG has value for exploitation and is an excellent choice for treating various diseases.