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Keywords = Platycodon grandiflorus root

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18 pages, 16224 KiB  
Article
Genome-Wide Identification of the CYP716 Gene Family in Platycodon grandiflorus (Jacq.) A. DC. and Its Role in the Regulation of Triterpenoid Saponin Biosynthesis
by Wuhua Zhang, Javed Iqbal, Zhihui Hou, Yingdong Fan, Jie Dong, Chengzhi Liu, Tao Yang, Daidi Che, Jinzhu Zhang and Dawei Xin
Plants 2024, 13(14), 1946; https://doi.org/10.3390/plants13141946 - 16 Jul 2024
Viewed by 532
Abstract
The main type of saponins occurring in the root of Platycodon grandiflorus (Jacq.) A. DC. are oleanolic acid glycosides. The CYP716 gene family plays a major role in catalyzing the conversion of β-amyrin into oleanolic acid. However, studies on the CYP716 genes in [...] Read more.
The main type of saponins occurring in the root of Platycodon grandiflorus (Jacq.) A. DC. are oleanolic acid glycosides. The CYP716 gene family plays a major role in catalyzing the conversion of β-amyrin into oleanolic acid. However, studies on the CYP716 genes in P. grandiflorus are limited, and its evolutionary history remains poorly understood. In this study, 22 PgCYP716 genes were identified, distributed among seven subfamilies. Cis-acting elements of the PgCYP716 promoters were mainly involved in plant hormone regulation and responses to abiotic stresses. PgCYP716A264, PgCYP716A391, PgCYP716A291, and PgCYP716BWv3 genes were upregulated in the root and during saponin accumulation, as shown by RNA-seq analysis, suggesting that these four genes play an important role in saponin synthesis. The results of subcellular localization indicated that these four genes encoded membrane proteins. Furthermore, the catalytic activity of these four genes was proved in the yeast, which catalyzed the conversion of β-amyrin into oleanolic acid. We found that the content of β-amyrin, platycodin D, platycoside E, platycodin D3, and total saponins increased significantly when either of the four genes was over expressed in the transgenic hair root. In addition, the expression of PgSS, PgGPPS2, PgHMGS, and PgSE was also upregulated while these four genes were overexpressed. These data support that these four PgCYP716 enzymes oxidize β-amyrin to produce oleanolic acid, ultimately promoting saponin accumulation by activating the expression of upstream pathway genes. Our results enhanced the understanding of the functional variation among the PgCYP716 gene family involved in triterpenoid biosynthesis and provided a theoretical foundation for improving saponin content and enriching the saponin biosynthetic pathway in P. grandiflorus. Full article
(This article belongs to the Special Issue Recent Advances in Horticultural Plant Genomics)
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Figure 1

Figure 1
<p>Identification of <span class="html-italic">PgCYP716s</span> in <span class="html-italic">P. grandiflorus</span>. (<b>A</b>) Multiple sequence alignment of the CYP450 domain of the PgCYP716 gene family. The asterisk denoted identical amino acids. (<b>B</b>) Phylogenetic tree of CYP716 proteins. The evolutionary tree was constructed based on the complete amino acid sequences of CYP716 proteins via MEGA 11 with the Maximum likelihood method. Bootstrap = 1000. CYP716s identified in this research are highlighted in red, while the filled arrowheads signify those CYP716s that have been functionally characterized in this study.</p>
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<p>Phylogenetic tree and gene structure analysis of 22 <span class="html-italic">PgCYP716</span> genes in <span class="html-italic">P. grandiflorus</span>. (<b>A</b>) The construction of a phylogenetic tree for the <span class="html-italic">PgCYP716</span> gene family. (<b>B</b>) The distribution of 10 conserved domains in the PgCYP716. A total of 10 motifs were identified, and each color represents one motif. (<b>C</b>) Gene structure analysis of <span class="html-italic">PgCYP716s</span>. (<b>D</b>) Conserved structural motifs of PgCYP716 proteins. Different colors represented different amino acids.</p>
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<p>Chromosome localization and collinearity analysis of <span class="html-italic">PgCYP716</span> gene family in <span class="html-italic">P. grandiflorus</span>. (<b>A</b>) Chromosomal distribution of 22 <span class="html-italic">PgCYP716</span> genes in <span class="html-italic">P. grandiflorus</span>. (<b>B</b>) The collinearity analysis of the CYP716 gene family in <span class="html-italic">P. grandiflorus</span>, <span class="html-italic">A. eleta</span>, and <span class="html-italic">A. thaliana</span>. The red triangle represented the chromosomal position of <span class="html-italic">PgCYP716s</span>.</p>
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<p>Analysis of cis-acting element in the promoter of <span class="html-italic">PgCYP716s</span>. (<b>A</b>) The number of different cis-acting elements in the <span class="html-italic">PgCYP716</span> gene promoter. (<b>B</b>) The positional distribution of different cis-acting elements in the <span class="html-italic">PgCYP716</span> gene promoter.</p>
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<p>The expression of <span class="html-italic">PgCYP716s</span> genes based on RNA-seq. (<b>A</b>) The expression of <span class="html-italic">PgCYP716s</span> at different levels of saponin accumulation. (<b>B</b>) The changes in the expression of <span class="html-italic">PgCYP716s</span> in different tissues. (<b>C</b>) The changes in the expression of <span class="html-italic">PgCYP716s</span> under MeJA treatment.</p>
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<p>The subcellular localization and expression analysis of <span class="html-italic">PgCYP716A264</span>, <span class="html-italic">PgCYP716A391</span>, <span class="html-italic">PgCYP716A291</span>, and <span class="html-italic">PgCYP716BWv3</span>. (<b>A</b>) <span class="html-italic">PgCYP716A264</span>, <span class="html-italic">PgCYP716A391</span>, <span class="html-italic">PgCYP716A291</span>, and <span class="html-italic">PgCYP716BWv3</span> genes encoded membrane proteins. The top, middle, and bottom represent bright, GFP, and merged fields, respectively. (<b>B</b>) Expression levels of the four genes in eight tissues. (<b>C</b>) Expression levels of the four genes under MeJA induction. Different letters indicated significant differences (<span class="html-italic">p &lt;</span> 0.05). Bar = 20 μm.</p>
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<p>In vivo enzymatic activity assay in yeast. (<b>A</b>) Detection of the yeast products using the vanillin-perchloric acid method indicated that the four enzymes could catalyze the production of oleanolic acid from β-amyrin. The top figure shows yeast-induced products, and the bottom figure shows oleanolic acid detected using the vanillin-perchloric acid method. (<b>B</b>) Schematic representation of the construction of PgbAS1 and the yeast heterologous expression vectors with four PgCYP716s. (<b>C</b>) HPLC analysis of yeast cultures indicated that PgCYP716A264, PgCYP716A391, PgCYP716A291, and PgCYP716BWv3 could produce oleanolic acid. (<b>D</b>) A summary of the biochemical reactions catalyzed by four PgCYP716 enzymes.</p>
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<p><span class="html-italic">PgCYP716A264</span>, <span class="html-italic">PgCYP716A391</span>, <span class="html-italic">PgCYP716A291</span>, and <span class="html-italic">PgCYP716BWv3</span> genes were functionally validated in the hairy roots of <span class="html-italic">P. grandiflorus</span>. (<b>A</b>) GFP fluorescence was detected in the hairy roots overexpressing <span class="html-italic">PgCYP716A264</span>, <span class="html-italic">PgCYP716A391</span>, <span class="html-italic">PgCYP716A291</span>, and <span class="html-italic">PgCYP716BWv3</span> genes. (<b>B</b>–<b>E</b>) Content of platycoside E, platycodin D3, β-amyrin, oleanolic acid, platycodin D, total saponin, soluble sugar, and starch in the WT and transgenic hairy roots. (<b>F</b>–<b>I</b>) qRT-PCR analysis of the expression of saponin synthesis pathway genes in overexpressed hairy roots. Asterisks indicated significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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10 pages, 2354 KiB  
Communication
Histone Deacetylase Inhibitor, Sodium Butyrate-Induced Metabolic Modulation in Platycodon grandiflorus Roots Enhances Anti-Melanogenic Properties
by Min-A Ahn, Jinsu Lee and Tae Kyung Hyun
Int. J. Mol. Sci. 2023, 24(14), 11804; https://doi.org/10.3390/ijms241411804 - 22 Jul 2023
Cited by 3 | Viewed by 1242
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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Figure 1

Figure 1
<p>Physiological response to NaB treatment in <span class="html-italic">P. grandiflorus</span>. (<b>A</b>) The acetylation status of histone H3 in NaB-treated <span class="html-italic">P. grandiflorus</span> roots. Changes in the levels of MDA (<b>B</b>) and photosynthesis (<b>C</b>) after NaB treatment was determined. The potential activity of PSII (Fv/Fo) and the maximum quantum efficiency of PS II photochemistry (Fv/Fm) were determined using a pulsed modular fluorometer. Means (±SE) with different letters (<span class="html-italic">p</span> &lt; 0.05, Duncan’s multiple range test) are significantly different. NaB_0, non-treated samples; NaB_100, samples treated with 100 µM NaB; NaB_200, samples treated with 200 µM NaB.</p>
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<p>The effect of NaB treatment on anti-melanogenic properties of <span class="html-italic">P. grandiflorus</span> roots. The inhibitory effects (<b>A</b>) and cytotoxic effects (<b>C</b>) of crude extracts and their solvent fractions on IBMX-induced melanin production in B16F10 melanoma cells were analyzed. (<b>B</b>) IC50 values of the IBMX-induced melanin production of EtOAc fractions. (<b>D</b>) Inhibitory effect of EtOAc fractions on tyrosinase activity. (<b>E</b>) The effect of EtOAc fractions on the levels of melanogenesis-related genes in IBMX-stimulated B16F10 cells. Each gene transcription level in each sample was expressed relative to that of the mock control (Mock). Means (±SE, three independent experiments) with asterisks (* <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01, <span class="html-italic">t</span>-test) or different letters (<span class="html-italic">p</span> &lt; 0.05, Duncan’s multiple range test) are significantly different. 0_Et, EtOAc fractions of the extract obtained from non-treated samples; 100_Et, EtOAc fractions of the extract obtained from 100 µM NaB-treated samples; 200_Et, EtOAc fractions of the extract obtained from 200 µM NaB-treated samples; TRP1, tyrosinase-related protein 1; TRP2, tyrosinase-related protein 2.</p>
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<p>NaB-induced differentially expressed genes (DEGs) in <span class="html-italic">P. grandiflorus</span> roots. Hierarchical analysis was conducted according to the gene expression patterns of DEGs, and gene ontology enrichment analysis for the biological processes was performed for DEGs in each cluster.</p>
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<p>The effect of NaB treatment on the phenylpropanoid pathway. (<b>A</b>) NaB-induced DEGs involved in the biosynthesis of phenylpropanoids. (<b>B</b>) qRT-PCR validation using selected genes. (<b>C</b>) The levels of dihydroquercetin, gallic acid, and 2, 4-dihydroxybenzoic acid were assessed using HPLC. Means (±SE, three independent experiments) with different letters (<span class="html-italic">p</span> &lt; 0.05, Duncan’s multiple range test) are significantly different. 0_Et, EtOAc fractions of the extract obtained from non-treated samples; 100_Et, EtOAc fractions of the extract obtained from 100 µM NaB-treated samples.</p>
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16 pages, 3832 KiB  
Article
Ameliorative Effects of Flavonoids from Platycodon grandiflorus Aerial Parts on Alloxan-Induced Pancreatic Islet Damage in Zebrafish
by Youn Hee Nam, Eun Bin Kim, Ji Eun Kang, Ju Su Kim, Yukyoung Jeon, Sung Woo Shin, Tong Ho Kang and Jong Hwan Kwak
Nutrients 2023, 15(7), 1798; https://doi.org/10.3390/nu15071798 - 6 Apr 2023
Cited by 4 | Viewed by 1685
Abstract
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 [...] Read more.
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 (18) 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)-β-D-glucopyranoside and apigenin 7-O-α-L-rhamnopyranosyl (1 → 2)-(6-O-acetyl)-β-D-glucopyranoside, respectively, by spectroscopic analysis. Compounds 1, 3, 4 and 68 yielded the recovery of injured pancreatic islets in zebrafish. Among them, compound 7 blocked KATP channels in pancreatic β-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. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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Graphical abstract

Graphical abstract
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<p>Extraction and solvent partition schemes of the root and aerial part of <span class="html-italic">P. grandiflorus</span>. (<b>A</b>) Extraction and fractionation scheme of the root; (<b>B</b>) extraction and fractionation scheme of the aerial part.</p>
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<p>Effect of extracts and solvent fractions from the aerial part and root of <span class="html-italic">P. grandiflorus</span> on an alloxan-induced diabetic zebrafish. (<b>A</b>) Change in pancreatic islet size caused by GLM, PgR-EtOH and PgA-EtOH extracts (10 μg/mL) and their solvent fractions (10 μg/mL); (<b>B</b>) relative 2-NBDG uptake in pancreatic islet caused by GLM, PgR-EtOH and PgA-EtOH extracts and their solvent fractions; (<b>C</b>) fluorescent microscopic images of the pancreatic islet (### <span class="html-italic">p</span> &lt; 0.001; compared to NOR) (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01; compared to AX) (+ <span class="html-italic">p</span> &lt; 0.05). Scale bar = 100 μm.</p>
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<p>Dose-dependent effects of the PgA-EtOAc fraction on alloxan-induced diabetic zebrafish. (<b>A</b>) Change in pancreatic islet size caused by GLM and PgA-EtOAc fraction; (<b>B</b>) relative 2-NBDG uptake in pancreatic islet caused by GLM and PgA-EtOAc; (<b>C</b>) fluorescent microscopic images of the pancreatic islet. Scale bar = 100 μm (## <span class="html-italic">p</span> &lt; 0.01, ### <span class="html-italic">p</span> &lt; 0.001; compared to NOR) (** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; compared to AX). Scale bar = μm.</p>
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<p>Dose-dependent effects of the PgA-BuOH fraction on alloxan-induced diabetic zebrafish. (<b>A</b>) Change in pancreatic islet size caused by the GLM and PgA-BuOH fraction; (<b>B</b>) relative 2-NBDG uptake in pancreatic islet caused by GLM and PgA-BuOH; (<b>C</b>) fluorescent microscopic images of the pancreatic islet. Scale bar = 100 μm (### <span class="html-italic">p</span> &lt; 0.001; compared to NOR) (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; compared to AX). Scale bar = μm.</p>
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<p>Structures of compounds <b>1</b>–<b>8</b> from the aerial part of <span class="html-italic">P. grandiflorus</span>.</p>
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<p>Key HMBC correlations of compounds <b>1</b> and <b>2</b>.</p>
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<p>Efficacy of compounds <b>1</b>–<b>8</b> on alloxan-induced diabetic zebrafish: changes in pancreatic islet size caused by GLM and compounds <b>1</b>–<b>8</b> (### <span class="html-italic">p</span> &lt; 0.001; compared to NOR) (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; compared to AX).</p>
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<p>Effect of the isolated compounds for K<sub>ATP</sub> channel on alloxan-induced diabetic zebrafish: the action of diazoxide (DZ) in the efficacy of compounds <b>1</b>, <b>3</b>, <b>4</b> and <b>6</b>–<b>8</b> (# <span class="html-italic">p</span> &lt; 0.05, ## <span class="html-italic">p</span> &lt; 0.01; compared to NOR, (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; compared to AX) (+ <span class="html-italic">p</span> &lt; 0.05, ++ <span class="html-italic">p</span> &lt; 0.01).</p>
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<p>Effect of isolated compounds (<b>3</b>, <b>4</b>, <b>6</b> and <b>7</b>) on the mRNA expressions of (<b>A</b>) <span class="html-italic">GCK</span>, (<b>B</b>) <span class="html-italic">GCKR</span>, (<b>C</b>) <span class="html-italic">GLIS3</span> and (<b>D</b>) <span class="html-italic">CDKN2B</span> in alloxan-induced zebrafish larvae. Values are expressed as means ± SD (# <span class="html-italic">p</span> &lt; 0.05, ### <span class="html-italic">p</span> &lt; 0.001; compared to NOR) (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001; compared to AX); <span class="html-italic">n</span> = 3.</p>
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16 pages, 3648 KiB  
Article
Enrichment of Wheat Bread with Platycodon grandiflorus Root (PGR) Flour: Rheological Properties and Microstructure of Dough and Physicochemical Characterization of Bread
by Yuanyuan Liu, Qian Zhang, Yuhan Wang, Pingkang Xu, Luya Wang, Lei Liu and Yu Rao
Foods 2023, 12(3), 580; https://doi.org/10.3390/foods12030580 - 29 Jan 2023
Cited by 3 | Viewed by 1858
Abstract
Platycodon grandiflorus (Jacq.) A.DC. root (PGR) flour is well known for its medical and edible values. In order to develop nutritionally fortified products, breads were prepared using wheat flour, partially replaced with PGR flour. The rheological properties and microstructure of dough and the [...] Read more.
Platycodon grandiflorus (Jacq.) A.DC. root (PGR) flour is well known for its medical and edible values. In order to develop nutritionally fortified products, breads were prepared using wheat flour, partially replaced with PGR flour. The rheological properties and microstructure of dough and the physicochemical characterization of bread were investigated. Results showed that lower level of PGR addition (3 and 6 g/100 g) would improve the baking performance of breads, while the higher level of PGR addition (9 g/100 g) led to smaller specific volume (3.78 mL/g), increased hardness (7.5 ± 1.35 N), and unpalatable mouthfeel (21.8% of resilience and 92.6% of springiness) since its negative effect on the viscoelasticity and microstructure of dough. Moreover, sensory evaluation analysis also showed that the PGR3 and PGR6 breads exhibited a similar flavor to the control bread, but the 9 g/100 g addition of PGR provided bread with an unpleasant odor through its richer volatile components. As expected, the phenolic content and antioxidant capacity of bread increased significantly (p < 0.05) as PGR flour was added to the bread formulation. The total phenolic content (TPC) ranged from 14.23 to 22.36 g GAE/g; thus, DPPH• and ABTS•+ scavenging capacity increased from 10.44 and 10.06 μg Trolox/g to 14.69 and 15.12 μg Trolox/g, respectively. Therefore, our findings emphasized the feasibility of PGR flour partially replacing wheat flour in bread-making systems. Full article
(This article belongs to the Special Issue Quality of Grains and Grain-Based Foods)
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Graphical abstract

Graphical abstract
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<p>CLSM micrographs of dough matrix and bread pictures. (<b>A1</b>–<b>A4</b>): PGR0; (<b>B1</b>–<b>B4</b>): PGR3; (<b>C1</b>–<b>C4</b>): PGR6; (<b>D1</b>–<b>D4</b>): PGR9. (<b>A</b>–<b>C</b>,<b>D</b>-<b>1</b>–<b>D</b>-<b>3</b>): CLSM micrographs; (<b>A</b>–<b>C</b>,<b>D</b>−<b>4</b>): Pictures of bread slices.</p>
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<p>OPLS-DA analysis result. PGR0: without PGR flour; PGR3: with 3 g/100 g PGR flour; PGR6: with 6 g/100 g PGR flour; PGR9: with 9 g/100 g PGR flour. (<b>A</b>): OPLS-DA score plot; (<b>B</b>): VIP; (<b>C</b>): Loading plot. SV: specific volume; MC: moisture content.</p>
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<p>Electronic tongue and electronic nose results of wheat bread enriched with different addition amounts of PGR flour. (<b>A</b>-<b>1</b>,<b>A</b>-<b>2</b>): PCA and DFA analysis of electronic tongue. (<b>B</b>-<b>1</b>–<b>B</b>-<b>3</b>): PCA, DFA analysis, and spider plot of an electronic nose. PGR0: without PGR flour; PGR3: with 3 g/100 g PGR flour; PGR6: with 6 g/100 g PGR flour; PGR9: with 9 g/100 g PGR flour.</p>
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<p>Volatile profiles of wheat bread enriched with different addition amounts of PGR flour. PGR0: without PGR flour; PGR3: with 3 g/100 g PGR flour; PGR6: with 6 g/100 g PGR flour; PGR9: with 9 g/100 g PGR flour.</p>
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<p>Total polyphenol content (TPC) and antioxidant capacity (DPPH·and ABTS·+) of wheat bread enriched with different addition amounts of PGR flour. PGR0: without PGR flour; PGR3: with 3 g/100 g PGR flour; PGR6: with 6 g/100 g PGR flour; PGR9: with 9 g/100 g PGR flour. Values with different letters are significantly different (<span class="html-italic">p</span> ≤ 0.05).</p>
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11 pages, 2533 KiB  
Article
Identification and Functional Characterization of FLOWERING LOCUS T in Platycodon grandiflorus
by Gayeon Kim, Yeonggil Rim, Hyunwoo Cho and Tae Kyung Hyun
Plants 2022, 11(3), 325; https://doi.org/10.3390/plants11030325 - 26 Jan 2022
Cited by 9 | Viewed by 3068
Abstract
Platycodon grandiflorus roots have been used as a foodstuff and traditional medicine for thousands of years in East Asia. In order to increase the root development of P. grandiflorus, cultivators removed the inflorescences, suggesting the possible negative effect of flowering on [...] Read more.
Platycodon grandiflorus roots have been used as a foodstuff and traditional medicine for thousands of years in East Asia. In order to increase the root development of P. grandiflorus, cultivators removed the inflorescences, suggesting the possible negative effect of flowering on root development. This indicates that the genetic improvement of P. grandiflorus by late flowering is a potential approach to increase productivity. However, nothing is known about key genes integrating multiple flowering pathways in P. grandiflorus. In order to fill this gap, we identified potential homologs of the FLOWERING LOCUS T (FT) gene in P. grandiflorus. The alignment with other FT members and phylogenetic analysis revealed that the P. grandiflorus FT (PlgFT) protein contains highly conserved functional domains and belongs to the FT-like clade. The expression analysis revealed spatial variations in the transcription of PlgFT in different organs. In addition, the expression level of PlgFT was increased by high temperature but not by photoperiodic light input signals, presumably due to lacking the CONSTANS binding motif in its promoter region. Furthermore, PlgFT induced early flowering upon its overexpression in P. grandiflorus, suggesting the functional role of PlgFT in flowering. Taken together, we functionally characterized PlgFT as a master regulator of P. grandiflorus flowering under inductive high temperature, which will serve as an important target gene for improving the root productivity. Full article
(This article belongs to the Special Issue Control of Flowering Time and Their Environmental Regulation in Crops)
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Figure 1

Figure 1
<p>Sequence alignment of PlgFT protein and other reported FT proteins. Red boxes indicate the conserved motifs and segments, including DPDxP, GXHR, segment A, and LYN. Blue boxes indicate key amino acids for flowering activator.</p>
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<p>Subcellular localization and yeast two-hybrid assay for <span class="html-italic">P</span>. <span class="html-italic">grandiflorus</span> FT. (<b>A</b>) Subcellular localization of PlgFT in <span class="html-italic">Nicotiana benthamiana</span> leaves. PlgFT recombinant proteins transiently expressed in <span class="html-italic">N</span>. <span class="html-italic">benthamiana</span> leaves through agro-infiltration. Scale bar = 20 μm. (<b>B</b>) Analysis of protein–protein interaction between PlgFT and Arabidopsis FD (AtAD) using yeast two-hybrid assay. Yeast cells (AH109) were grown on SD agar medium lacking either Trp and Leu (−LT) or Trp, Leu, and His (−LTH).</p>
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<p>Expression pattern of <span class="html-italic">PlgFT</span> in different organs (<b>A</b>) and flower development stages (<b>B</b>). Expression levels of <span class="html-italic">PlgFT</span> were normalized to actin. Data represent the means ± SD of three independent experiments. Different letters correspond to means that are statistically different (<span class="html-italic">p</span> &lt; 0.05). The scale bars represent 10 cm (<b>A</b>) and 1 cm (<b>B</b>).</p>
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<p>Diurnal expression pattern of <span class="html-italic">PlgFT</span> under different photoperiodic conditions. The expression levels of <span class="html-italic">PlgFT</span> were measured every 4 h throughout the diurnal cycle in LD and SD conditions. Expression levels of <span class="html-italic">PlgFT</span> were normalized to actin. Values represent three independent replicates ± SD. Uppercase denotes significance (<span class="html-italic">p</span> &lt; 0.05) between the expression levels under LD, whereas lowercase denotes significance (<span class="html-italic">p</span> &lt; 0.05) between the expression levels under SD.</p>
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<p>Regulation of <span class="html-italic">PlgFT</span> expression by GA<sub>3</sub> (<b>A</b>) and high-temperature conditions (<b>B</b>). Two-month-old plants were treated with GA<sub>3</sub> or high temperature (30 °C). The expression levels of <span class="html-italic">PlgFT</span> were normalized to actin. Values represent three independent replicates ± SD. Uppercase denotes significance (<span class="html-italic">p</span> &lt; 0.05) between the expression levels after treatment of GA3 or high temperature (30 °C), whereas lowercase denotes significance (<span class="html-italic">p</span> &lt; 0.05) between the expression levels after treatment of mock or normal temperature (22 °C).</p>
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<p>Ectopic expression of <span class="html-italic">PlgFT</span> in <span class="html-italic">P</span>. <span class="html-italic">grandiflorus</span> induced early flowering. (<b>A</b>) The expression of <span class="html-italic">PlgFT-GFP</span> in the selected transgenic plants was confirmed by RT-PCR. Phenotypes of TC and <span class="html-italic">PlgFT-GFP</span> overexpression plants (PlgFT-OX) grown in the in vitro condition (<b>B</b>) and soil (<b>C</b>). Scale bar = 1 cm (<b>B</b>) or 10 cm (<b>C</b>).</p>
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12 pages, 2462 KiB  
Article
Immune-Enhancing Effects of Red Platycodon grandiflorus Root Extract via p38 MAPK-Mediated NF-κB Activation
by Eun-Jung Park, You-Suk Lee, Sung Min Kim, Ah Jin Jung, Jeong-Hyun Yoo, Sung-Hyen Lee, Hyun Cheol Jeong and Hae-Jeung Lee
Appl. Sci. 2020, 10(16), 5457; https://doi.org/10.3390/app10165457 - 7 Aug 2020
Cited by 11 | Viewed by 2949
Abstract
Platycodongrandiflorus (PG) root extract has been widely used as an oriental herbal medicine. Red PG root extract (RPGE), which is made by steaming and drying PG several times, contains more saponin than raw (white) PG. Although RPGE has been known to have [...] Read more.
Platycodongrandiflorus (PG) root extract has been widely used as an oriental herbal medicine. Red PG root extract (RPGE), which is made by steaming and drying PG several times, contains more saponin than raw (white) PG. Although RPGE has been known to have anti-inflammatory activity, the effects of RPGE on the immune-enhancing response remain unclear. In this study, we aimed to investigate the immune-enhancing effects of RPGE and its mechanism in macrophage cells and splenocytes. Our results revealed that cell proliferation of both macrophages and splenocytes correlate positively with the concentration of RPGE. Moreover, RPGE treatment increased the phagocytic activity of macrophage cells, as well as nitric oxide and cytokines production. Furthermore, RPGE induced phosphorylation of the p38 mitogen-activated protein kinase, which contributed to nuclear factor-kappa B activation. Thus, our findings suggest that RPGE may be a potential functional food for improving immune function. Full article
(This article belongs to the Special Issue Functional Food and Chronic Disease)
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<p>Effect of Red <span class="html-italic">Platycodon grandiflorus</span> Root Extract (RPGE) on cell viability in RAW 264.7 cells. (<b>a</b>) RPGE-concentrate (RPGE-C); (<b>b</b>) RPGE-powder (RPGE-P). The results are expressed as relative values to that of the vehicle-treated cells (vehicle control, VC), which is set to 100%. The data are represented as the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 when compared with the VC.</p>
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<p>Effect of RPGE on the phagocytic activity of RAW 264.7 cells. (<b>a</b>) RPGE-C; (<b>b</b>) RPGE-P. PI, phagocytosis inhibitor. Values are represented as the mean ± SEM. ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 when compared with the VC treated with an <span class="html-italic">E. coli</span> suspension.</p>
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<p>Effect of RPGE on NO production and related mRNA expression in RAW 264.7 cells. (<b>a</b>–<b>c</b>) RPGE-C; (<b>d</b>–<b>f</b>) RPGE-P. (<b>a</b>,<b>d</b>) NO production; (<b>b</b>,<b>e</b>) <span class="html-italic">Nos2</span> mRNA expression level; (<b>c</b>,<b>f</b>) <span class="html-italic">Ptgs2</span> mRNA expression level. NO, Nitric oxide. All gene expression values were normalized to <span class="html-italic">Actb</span>, and the results were expressed as relative values to that of the VC, which is set to 1. The data are represented as the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 when compared with the VC.</p>
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<p>Effect of RPGE on cytokine levels in RAW 264.7 cells. (<b>a</b>–<b>d</b>) RPGE-C; (<b>e</b>–<b>h</b>) RPGE-P. (<b>a</b>,<b>e</b>) <span class="html-italic">Tnf-α</span> mRNA expression level; (<b>b</b>,<b>f</b>) <span class="html-italic">IL-1b</span> mRNA expression level; (<b>c</b>,<b>g</b>) <span class="html-italic">IL-6</span> mRNA expression level. The gene expression values were normalized to <span class="html-italic">Actb</span>, and the results were expressed as relative values to that of the VC, which is set to 1. (<b>d</b>,<b>h</b>) IL-6 protein levels in the culture supernatant. All data are represented as the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 when compared with the VC.</p>
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<p>Effect of RPGE on NF-κB activation in RAW 264.7 cells. (<b>a</b>) RPGE-C; (<b>c</b>) RPGE-P. Luciferase activity was expressed as a relative value to that of the VC, which is set to 100%. The figures show the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001. (<b>b</b>) The cells were treated with 500 μg/mL of RPGE-C for the indicated times or indicated concentrations for 60 min prior to Western blot analysis; (<b>d</b>) The cells were treated with 500 μg/mL of RPGE-P for the indicated times or indicated concentrations prior to Western blot analysis.</p>
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<p>Effect of RPGE on MAPK signaling in RAW 264.7 cells. (<b>a</b>) The cells were treated with 500 μg/mL of RPGE-C for the indicated times or indicated concentrations for 60 min prior to Western blot analysis; (<b>b</b>) The cells were treated with 500 μg/mL of RPGE-P for the indicated times or indicated concentrations for 60 min prior to Western blot analysis; (<b>c</b>) The time–response and concentration–response relationships of RPGE-C were represented as heat maps. (<b>d</b>) The time–response and concentration–response relationships of RPGE-P were represented as heat maps.</p>
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<p>Effect of MAPK signaling on NF-κB activation in RAW 264.7 cells. (<b>a</b>) without RPGEs; (<b>b</b>) RPGE-C; (<b>c</b>) RPGE-P. Luciferase activity was expressed as a relative value to that of the VC (-), which is set to 100%. The figures show the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 when compared with cells treated with RPGEs alone. SB203580, p38 MAPK inhibitor and SP600125, JNK inhibitor.</p>
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<p>Effect of RPGE on cell viability and secretion of IL-10 in mouse splenocytes. (<b>a</b>) Mouse splenocytes were incubated with Con A (5 μg/mL), LPS (1 μg/mL), or various concentrations of RPGE-C; (<b>c</b>) Mouse splenocytes were incubated with Con A (5 μg/mL), LPS (1 μg/mL), or various concentrations of RPGE-P. Con A, Concanavalin A; LPS, lipopolysaccharide. The results were expressed as a relative value to that of VC, which is set to 100%. The data are represented as the mean ± SEM. ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 as when compared with the VC. (<b>b</b>) IL-10 protein level (RPGE-C); (<b>d</b>) IL-10 protein level (RPGE-P). All data are represented as the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 as when compared with the VC.</p>
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13 pages, 2927 KiB  
Article
Dietary Platycodon grandiflorus Attenuates Hepatic Insulin Resistance and Oxidative Stress in High-Fat-Diet Induced Non-Alcoholic Fatty Liver Disease
by Weixin Ke, Pan Wang, Xuehua Wang, Xiaolu Zhou, Xiaosong Hu and Fang Chen
Nutrients 2020, 12(2), 480; https://doi.org/10.3390/nu12020480 - 14 Feb 2020
Cited by 25 | Viewed by 4059
Abstract
The root of Platycodon grandiflorus (PG), with hepatoprotective and anti-oxidation effects, has a long history of being used as food and herbal medicine in Asia. However, the mechanism of PG against non-alcoholic fatty liver disease (NAFLD) is still not clear. The aim of [...] Read more.
The root of Platycodon grandiflorus (PG), with hepatoprotective and anti-oxidation effects, has a long history of being used as food and herbal medicine in Asia. However, the mechanism of PG against non-alcoholic fatty liver disease (NAFLD) is still not clear. The aim of this study was to investigate the mechanism of PG suppressing the development of NAFLD induced by a high-fat diet (HFD) in mice. Male C57BL/6J mice were fed with either a standard chow diet or a HFD, either supplemented with or without PG, for 16 weeks. Serum lipids, liver steatosis, oxidative stress and insulin sensitivity were determined. Expressions or activities of hepatic enzymes in the related pathways were analyzed to investigate the mechanisms. PG significantly reduced HFD-induced hepatic injury and hyperlipidemia, as well as hepatic steatosis via regulating phosphorylation of acetyl-CoA carboxylase (p-ACC) and expression of fatty acid synthase (FAS). In addition, PG ameliorated oxidative stress by restoring glutathione (GSH) content and antioxidant activities, and improved insulin sensitivity by regulating the PI3K/Akt/GSK3β signaling pathway. Our data showed that dietary PG have profound effects on hepatic insulin sensitivity and oxidative stress, two key factors in the pathogenesis of NAFLD, demonstrating the potential of PG as a therapeutic strategy for NAFLD. Full article
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<p>PG reduced fat accumulation and liver injury in HFD mice: (<b>A</b>) body weight and (<b>B</b>) liver weight at the end of the experiment. (<b>C</b>) Mean energy intake per mouse per day. (<b>D</b>) Typical liver morphological images (scale: 1 cm). (<b>E</b>) Serum AST and (<b>F</b>) ALT levels. a, b, c means in the same bar without a common letter differ at <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>PG ameliorated steatosis and regulated lipid metabolism genes. (<b>A</b>) TG and (<b>B</b>) TC content in liver. (<b>C</b>,<b>D</b>) Hepatic steatosis determined by H&amp;E (C) and Oil Red O (D) staining (scale: 50 μm) with steatosis scores shown in (<b>E</b>) and (<b>F</b>). (<b>G</b>) Western blot analysis for ACC, p-ACC, and FAS in liver tissues. (<b>H</b>) Fold change in expression of p-ACC/ACC and FAS/β-actin relative to SD group. TG, total triacylglycerol; TC, total cholesterol; ACC, acetyl-CoA carboxylase; p-ACC, phospho-ACC; FAS, fatty acid synthase. a, b, c means in the same bar without a common letter differ at <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>PG improved insulin sensitivity and glucose tolerance in HFD-fed mice. (<b>A</b>) Fasting blood glucose level. (<b>B</b>) Fasting serum insulin level. (<b>C</b>) HOMA-IR index. (<b>D</b>) Serum glucose level curves of ipGTT. (<b>E</b>) Area under the curve (AUC) of the blood glucose during ipGTT. a, b, c means in the same bar without a common letter differ at <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>PG enhances hepatic insulin signaling PI3K/Akt/ GSK3β pathway in HFD-fed mice. (<b>A</b>) Western blot analysis for PI3K, p-PI3K, Akt, p-Akt, GSK3β, p-GSK3β, GS, and p-GS in liver tissues. (<b>B</b>) Fold change in expression of p-PI3K/PI3K, p-Akt/Akt, p-GSK3β/GSK3β, and p-GS/GS by densitometry relative to SD group. a, b, c means in the same bar without a common letter differ at <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>PG reduces hepatic oxidative stress in HFD-fed mice. (<b>A</b>) Liver GSH content. Activities of (<b>B</b>) GSH-Px, (<b>C</b>) SOD1, and (<b>D</b>) CAT, ns means no significant difference. (<b>E</b>) mRNA expression of CPT1 in liver analyzed by RT-qPCR. (<b>F</b>) Western blot analysis for HO-1, NQO1, and β-actin in liver tissues. (<b>G</b>) Fold change in relative expression of HO-1/β-actin and NQO1/β-actin in protein level. a, b, c means in the same bar without a common letter differ at <span class="html-italic">p</span> &lt; 0.05.</p>
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12 pages, 219 KiB  
Article
Intervention Study on the Efficacy and Safety of Platycodon grandiflorus Ethanol Extract in Overweight or Moderately Obese Adults: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Trial
by Ye Jin Kim, Eun-Young Kwon, Ji-Won Kim, Youngmi Lee, Ri Ryu, Jongbok Yun, Manheun Kim and Myung-Sook Choi
Nutrients 2019, 11(10), 2445; https://doi.org/10.3390/nu11102445 - 14 Oct 2019
Cited by 9 | Viewed by 2965
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Nutraceutical, Nutrition Supplements and Human Health)
2517 KiB  
Article
Platycodon grandiflorus Root Extract Improves Learning and Memory by Enhancing Synaptogenesis in Mice Hippocampus
by Jin-il Kim, Seong Gak Jeon, Kyoung Ah Kim, Jwa-Jin Kim, Eun Ji Song, Yukyoung Jeon, Eunbin Kim, Kyung Bok Lee, Jong Hwan Kwak and Minho Moon
Nutrients 2017, 9(7), 794; https://doi.org/10.3390/nu9070794 - 23 Jul 2017
Cited by 17 | Viewed by 7635
Abstract
Platycodon grandiflorus (Jacq.) A.DC. (PG) has long been used as an ingredient of foods and is known to have beneficial effects on cognitive functions as well. The present study examined the effect of each PG extract (PGE) from root, aerial part, and seeds [...] Read more.
Platycodon grandiflorus (Jacq.) A.DC. (PG) has long been used as an ingredient of foods and is known to have beneficial effects on cognitive functions as well. The present study examined the effect of each PG extract (PGE) from root, aerial part, and seeds on cognitive functions in mice. Changes in spatial learning and memory using a Y-maze test, and markers of adult hippocampal neurogenesis and synaptogenesis were examined. Moreover, changes in neuritogenesis and activation of the ERK1/2 pathway were investigated. Results indicated that mice administered PGE (root) showed increased spontaneous alternation in the Y-maze test and synaptogenesis in the hippocampus. In addition, PGE (root) and platycodin D, the major bioactive compound from the PG root, significantly stimulated neuritic outgrowth by phosphorylation of the ERK1/2 signaling pathway in vitro. These results indicate that the PGE (root), containing platycodin D, enhances cognitive function through synaptogenesis via activation of the ERK1/2 signaling pathway. Full article
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<p>Oral administration of PGEs (100 mg/kg/day) for 15 days. PGEs are classified into three different parts including PGE (root), PGE (aerial part), and PGE (seed). The cognition of mice treated with three different PGEs underwent a Y-maze test. After the behavioral experiment, animals administered with PGE (root) were sacrificed and brains were isolated for analysis. Subsequently, immunohistochemistry of brains was performed using DCX antibody and immunoblotting with SYN antibody. PGE, <span class="html-italic">Platycodon grandiflorus</span> extract. DCX, doublecortin. SYN, synaptophysin.</p>
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<p>Behavioral test to determine the enhancing effect of PGE on cognition. The Y-maze test shows no significant influence of PGE on total arm entry regardless of the PG structural part administered (<b>a</b>). The PGE (root)-administered group shows a significant increase in spontaneous alternations, indicating PGE (root) significantly increased spatial learning and memory. PGE (aerial part) and PGE (seed)-administered groups show no significant increase of spontaneous alternation (<b>b</b>). Values are the mean + SEM. *** <span class="html-italic">p</span> &lt; 0.05 compared to the vehicle-treated control group. PGE, <span class="html-italic">Platycodon grandiflorus</span> extract.</p>
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<p>HPLC chromatograms of the EtOH extract of PG. (<b>a</b>) Structures of platycodin D and platycodin D2, (<b>b</b>) HPLC chromatograms of the root extract, and (<b>c</b>) HPLC chromatograms of standard compounds, platycodin D, and platycodin D2. HPLC analysis was carried out using a gradient elution on a phenomenex Kinetex RP-C18 column (5 µ, 100 A, 150 × 4.6 mm) at a flow rate of 1.0 mL/min, and with UV 210 nm detection.</p>
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<p>Immunohistochemical analysis using DCX antibody. DCX is a marker of neurogenesis, especially neuronal fate specification. The PGE (root)-administered group shows a similar number of DCX (+) cells per unit length compared to the control group. Values are the mean + SEM. Scale bar = 50 μm. PGE, <span class="html-italic">Platycodon grandiflorus</span> extract. DCX, doublecortin.</p>
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<p>Immunoblotting analysis of synaptophysin expression in the hippocampus and frontal cortex after PGE (root)-administration. The PGE (root)-administered group shows a significantly higher expression of SYN in hippocampus than the controls. The PGE (root)-administered group shows no significant difference in the frontal cortex compared to the controls. Values are the mean + SEM. * <span class="html-italic">p &lt;</span> 0.05 compared to the vehicle-treated control group. PGE, <span class="html-italic">Platycodon grandiflorus</span> extract. SYN, synaptophysin.</p>
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<p>In vitro assay to confirm PGE (root)-induced neuritogenesis in PC12 cells. PC12 cells were treated with 10 μg/mL PGE (root) for 24 h and the cells show a significant increase in neurite length compared to the controls. Values are the mean + SEM. *** <span class="html-italic">p &lt;</span> 0.05 compared to the vehicle-treated control group. Scale bar = 20 μm. PGE, <span class="html-italic">Platycodon grandiflorus</span> extract.</p>
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<p>Immunoblotting of PGE (root) treated PC12 cells with ERK1/2. Cells were treated with PGE (root) for 24 h and assayed by western blot using anti-ERK1/2 antibodies and anti-phospho-ERK1/2 antibodies (Thr202/Tyr204). PGE-(root) treated PC12 cells show a significant increase in ERK1/2 phosphorylation. Values are the mean + SEM. *** <span class="html-italic">p &lt;</span> 0.05 compared to the vehicle-treated control group. PGE, <span class="html-italic">Platycodon grandiflorus</span> extract.</p>
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<p>Measurement of neurite length to confirms the effects of bioactive molecules of PG in PC12 cells. PC12 cells were treated with 10 μg/mL platycodin D or platycodin D2 for 24 h and neurite lengths measured. Platycodin D, but not platycodin D2, treated PC12 cells show significantly increased neurite lengths. Scale bar = 20 μm. Values are the mean + SEM. *** <span class="html-italic">p &lt;</span> 0.05 compared to the vehicle-treated control group.</p>
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Article
Platycodon grandiflorus Root Extract Attenuates Body Fat Mass, Hepatic Steatosis and Insulin Resistance through the Interplay between the Liver and Adipose Tissue
by Ye Jin Kim, Ji-Young Choi, Ri Ryu, Jeonghyeon Lee, Su-Jung Cho, Eun-Young Kwon, Mi-Kyung Lee, Kwang-Hyeon Liu, Yu Rina, Mi-Kyung Sung and Myung-Sook Choi
Nutrients 2016, 8(9), 532; https://doi.org/10.3390/nu8090532 - 30 Aug 2016
Cited by 31 | Viewed by 7618
Abstract
The Platycodon grandiflorus root, a Korean medicinal food, is well known to have beneficial effects on obesity and diabetes. In this study, we demonstrated the metabolic effects of P. grandiflorus root ethanol extract (PGE), which is rich in platycodins, on diet-induced obesity. C57BL/6J [...] Read more.
The Platycodon grandiflorus root, a Korean medicinal food, is well known to have beneficial effects on obesity and diabetes. In this study, we demonstrated the metabolic effects of P. grandiflorus root ethanol extract (PGE), which is rich in platycodins, on diet-induced obesity. C57BL/6J mice (four-week-old males) were fed a normal diet (16.58% of kilocalories from fat), high-fat diet (HFD, 60% of kilocalories from fat), and HFD supplemented with 5% (w/w) PGE. In the HFD-fed mice, PGE markedly suppressed the body weight gain and white fat mass to normal control level, with simultaneous increase in the expression of thermogenic genes (such as SIRT1, PPARα, PGC1α, and UCP1), that accompanied changes in fatty acid oxidation (FAO) and energy expenditure. In addition, PGE improved insulin sensitivity through activation of the PPARγ expression, which upregulates adiponectin while decreasing leptin gene expression in adipocytes. Furthermore, PGE improved hepatic steatosis by suppressing hepatic lipogenesis while increasing expression of FAO-associated genes such as PGC1α. PGE normalized body fat and body weight, which is likely associated with the increased energy expenditure and thermogenic gene expression. PGE can protect from HFD-induced insulin resistance, and hepatic steatosis by controlling lipid and glucose metabolism. Full article
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<p>Effects of dietary PGE on body weight gain, plasma lipid profiles, insulin resistance, and glucose tolerance via modulating hepatic glucose-regulating enzyme activities in HFD-fed C57BL/6J mice. The data are the mean ± SEM (<span class="html-italic">n</span> = 10). (<b>A</b>) Changes in the body weight, food intake, and food efficiency ratio (FER); (<b>B</b>) levels of plasma total, HDL, and non-HDL cholesterol, AI, TG, FFA, Apo A-1, and Apo B; (<b>C</b>) levels of plasma resistin, leptin, TNF-α, and PAI-1; (<b>D</b>) blood glucose levels after 12 h of fasting; (<b>E</b>) plasma insulin and glucose levels after 12 h of fasting and the HOMA-IR calculated using the fasting blood glucose and insulin levels; (<b>F</b>) glucose tolerance; and (<b>G</b>) activities of the glucose-regulating enzymes G6Pase and PEPCK. ND, mice fed a normal diet; HFD, mice fed a high-fat diet (HFD) alone; PGE, <span class="html-italic">Platycodon grandiflorus</span> root extract (5%, <span class="html-italic">w</span>/<span class="html-italic">w</span>)-treated HFD-fed mice. B.W., body weight, AI, atherogenic index, ((Total-C)-(HDL-C))/HDL-C.</p>
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<p>Effects of PGE on body fat mass, energy expenditure, and mRNA expression of adipogenic and thermogenic genes via regulation of fatty acid oxidation in epididymal white adipose tissue in HFD-fed C57BL/6J mice. The data are the mean ± SEM (<span class="html-italic">n</span> = 10). (<b>A</b>) The weight of adipose tissue; (<b>B</b>) representative photographs of adipocytes in the epididymal WAT of the mice, 200× magnification; and (<b>C</b>) energy expenditure and oxygen consumption (<span class="html-italic">V</span>o<sub>2</sub>). Adipogenesis (<b>D</b>); thermogenesis (<b>E</b>); and adipokine (<b>F</b>) related gene expression. (<b>G</b>) Western blot analysis of β-actin, PPARγ, CD36, <span class="html-italic">PGC1</span>α, and CPT2 expression. ND, mice fed a normal diet; HFD, mice fed a high-fat diet (HFD) alone; PGE, <span class="html-italic">Platycodon grandiflorus</span> root extract (5%, <span class="html-italic">w</span>/<span class="html-italic">w</span>)-treated HFD-fed mice; WAT, white adipose tissue.</p>
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<p>Effects of PGE on body fat mass, energy expenditure, and mRNA expression of adipogenic and thermogenic genes via regulation of fatty acid oxidation in epididymal white adipose tissue in HFD-fed C57BL/6J mice. The data are the mean ± SEM (<span class="html-italic">n</span> = 10). (<b>A</b>) The weight of adipose tissue; (<b>B</b>) representative photographs of adipocytes in the epididymal WAT of the mice, 200× magnification; and (<b>C</b>) energy expenditure and oxygen consumption (<span class="html-italic">V</span>o<sub>2</sub>). Adipogenesis (<b>D</b>); thermogenesis (<b>E</b>); and adipokine (<b>F</b>) related gene expression. (<b>G</b>) Western blot analysis of β-actin, PPARγ, CD36, <span class="html-italic">PGC1</span>α, and CPT2 expression. ND, mice fed a normal diet; HFD, mice fed a high-fat diet (HFD) alone; PGE, <span class="html-italic">Platycodon grandiflorus</span> root extract (5%, <span class="html-italic">w</span>/<span class="html-italic">w</span>)-treated HFD-fed mice; WAT, white adipose tissue.</p>
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<p>Effects of PGE treatment on hepatic steatosis-related markers in HFD-fed C57BL/6J mice. The data are the mean ± SEM (<span class="html-italic">n</span> = 10). (<b>A</b>) The weight of the liver and plasma levels of hepatic cholesterol, TG, and FFA; (<b>B</b>) hematoxylin and eosin (H &amp; E)-stained transverse sections of the liver, 1000× magnification; (<b>C</b>) levels of the hepatic lipotoxicity markers GOT and GPT; (<b>D</b>) Lipogenesis-related gene expression; and (<b>E</b>) Hepatic lipid-regulating enzyme activities in the HFD-fed mice. ND, mice fed a normal diet; HFD, mice fed a high-fat diet (HFD) alone; PGE, <span class="html-italic">Platycodon grandiflorus</span> root extract (5%, <span class="html-italic">w</span>/<span class="html-italic">w</span>)-treated HFD-fed mice.</p>
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<p>Proposed mechanism for PGE regarding anti-obesity effects. Schematic representation of the role of PGE in amelioration of obesity. PGE can contribute to browning of WAT in diet-induced obese mice through increasing fatty acid oxidation in mitochondria, which promotes energy expenditure. In addition, PPARγ activation by PGE controls adipokines, specifically the insulin-sensitizing hormones adiponectin and leptin. In the liver, PGE downregulates the mRNA expression of lipogenesis and cholesterol synthesis transcription factors, SREBP1 and SREBP2, thereby reducing hepatic steatosis and insulin resistance. PPARγ, peroxisome proliferator-activated receptor γ; SREBP1a, -1c, and -2, sterol regulatory element-binding proteins 1a, 1c, and 2; FAS, fatty acid synthase; ACC, acetyl-CoA carboxylase; SCD1, stearoyl-CoA desaturase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; ACAT, acetyl-CoA acetyltransferase; <span class="html-italic">SIRT1</span>, sirtuin 1; <span class="html-italic">PPAR</span>α, peroxisome proliferator-activated receptor α; <span class="html-italic">PGC1</span>α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; <span class="html-italic">UCP1</span>, uncoupling protein 1; TNF-α, tumor necrosis factor-α; CPT2, carnitine palmitoyltransferase 2.</p>
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