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PubMed2026

Multidimensional Proteomics Reveals the Pro-apoptotic Mechanism of Platycodin D: Targeting RFC4 to Regulate the Notch Signaling Axis in Non-Small Cell Lung Cancer.

Platycodin D (PD), a major bioactive saponin isolated from the traditional Chinese medicine Platycodon grandiflorus, has shown promising therapeutic potential against non-small cell lung cancer (NSCLC). However, the functional mechanisms of PD in NSCLC progression remains unclear. This study aimed to explore the pharmacological mechanism of PD against NSCLC. Thermal proteome profiling approach, molecular docking, cellular thermal shift assay and peptide-centric local stability assay were employed to identify the potential binding target of PD. Subsequent Western Blot and immunoprecipitation-Western Blot experiments were conducted to investigate the downstream signaling pathways of the target. Furthermore, proteomic and ubiquitinomic profiling of PD-treated cells were performed to investigate its functions on global. replication factor C subunit 4 (RFC4) was identified as a potential binding target of PD by thermal proteome profiling and their binding sites were further exposed by peptide-centric local stability assay. PD-RFC4 complex promotes the degradation of Notch1 and Notch3 by reducing nuclear entry of their domains. Compared with control treatment, the differentially expressed proteins induced by PD were found to be primarily involved in ferroptosis, ubiquitination, platinum drug resistance, and ribosome-related processes. The ubiquitin proteome analysis revealed that proteins associated with the Notch pathway underwent ubiquitin modifications. PD binds to RFC4 and inhibits its activity, leading to downregulation of the Notch signaling pathway, ultimately triggering cancer cell apoptosis. PD is a natural product with potential therapeutic value for NSCLC.

Saponins↗

PubMed2005

Prostaglandin-H-synthase (PGHS)-1 and -2 microtiter assays for the testing of herbal drugs and in vitro inhibition of PGHS-isoenzyms by polyunsaturated fatty acids from Platycodi radix.

In order to test inhibition of prostaglandin-H-synthase-1 and -2 (PGHS-1 and -2) by plant extracts, we have established two enzyme based in vitro assays with enzyme immunoassay (EIA) evaluation. The assays have been evaluated with known synthetic inhibitors and with plant extracts. In a screening of traditionally used Chinese herbs for anti-inflammatory activity, a series of n-hexane and dichloromethane extracts showed significant inhibitory effect in comparison with the known specific PGHS-2 inhibitors NS-398 (IC(50) = 2.6 microM) and nimesulide (IC(50) = 36 microM). The lipophilic extracts of the Chinese drug Jiengeng, the dried roots of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae), showed good inhibitory activity against both PGHS isoenzymes. The directly prepared DCM-extract exhibited better activity against PGHS-2 (IC(50) = 4.0 microg/ml) than against PGHS-1 (IC(50) = 17.6 microg/ml). We identified fatty acids as main active constituents and quantified them. Linoleic acid showed the highest content (ca. 20% of the dried extract) and a high and preferential PGHS-2 inhibitory activity (IC(50) (PGHS-1) = 20 microM; IC(50) (PGHS-2) = 2 microM). The comparison of the concentration of linoleic acid and the inhibitory activity of the direct DCM-extract showed, that linoleic acid is mainly responsible for the in vitro activity of the extract on PGHS-2.

Animals↗

PubMed2006

7-Polyacylated delphinidin 3,7-diglucosides from the blue flowers of Leschenaultia cv. Violet Lena.

The triacyl anthocyanins, Leschenaultia blue anthocyanins 1 and 2 (LBAs 1 and 2) were isolated from the blue flowers of Leschenaultia R. Br. cv. Violet Lena (Goodeniaceae), in which LBA 1 was present as a dominant pigment. The structure of LBA 1 was elucidated to be delphinidin 3-O-[6-O-(malonyl)-beta-D-glucopyranoside]-7-O-[6-O-(4-O-(6-O-(4-O-(beta-D-glucopyranosyl)-trans-caffeoyl)-beta-D-glucopyranosyl)-trans-caffeoyl)-beta-D-glucopyranoside] by application of chemical and spectroscopic methods. Since LAB 2 was isolated in small amount, its structure was tentatively assigned as either delphinidin 3-(malonylglucoside)-7-[(glucosyl-p-coumaroyl)-(glucosylcaffeoyl)-glucoside] or delphinidin 3-(malonyl-glucoside)-7-[(glucosyl-caffeoyl)(glucosyl-p-coumaroyl)-glucoside]. This is the first report of the occurrence of 7-polyacylated anthocyanins in the family of Goodeniaceae, although others have been found in the families of the Ranunculaceae, Campanulaceae, and Compositae. Moreover, delphinidin 3-glycoside-7-di-(glucosylcaffeoyl)-glucoside has been reported only in the flowers of Platycodon grandiflorum (Campanulaceae). From a chemotaxonomical viewpoint, the Goodeniaceae may be closely related to the Campanulaceae.

Acylation↗

PubMed2002

Protective effect of Platycodi radix on carbon tetrachloride-induced hepatotoxicity.

The protective effects of a Platycodi radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae) on carbon tetrachloride (CC14)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with CK prior to the administration of CC14 significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with CK also significantly prevented the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver of CC14-intoxicated mice. However, hepatic reduced glutathione levels and glutathione S-transferase activities were not affected by treatment with CK alone. CC14-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of CK on the cytochrome P450 (P450) 2E1, the major isozyme involved in CC14 bioactivation were also investigated. Treatment of mice with CK resulted in a significant decrease of P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. CK showed antioxidant effects in FeCl2-ascorbate-induced lipid peroxidation in mice liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effects of CK against CC14-induced hepatotoxicity possibly involve mechanisms related to its ability to block P450-mediated CC14 bioactivation and free radical scavenging effects.

Animals↗

PubMed1999

Differentiation of medicinal Codonopsis species from adulterants by polymerase chain reaction-restriction fragment length polymorphism.

DNA sequence analysis of rDNA internal transcribed spacer (ITS) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were exploited for their applications in differentiating medicinal species Codonopsis pilosula, C. tangshen, C. modesta, and C. nervosa var. macrantha, from two related adulterants Campanumoea javania and Platycodon grandiflorus. The data demonstrated that the rDNA ITSI and ITSII sequences of the four Codonopsis are highly homologous but not identical, and are significantly different from those of the two adulterants. The sequence difference allows effective and reliable differentiation of Codonopsis from the adulterants by PCR-RFLP.

Asteraceae↗

PubMed2004

Antinociceptive profiles of platycodin D in the mouse.

Platycodin D (PD), one of several triterpene saponins, was isolated from roots of Platycodon grandiflorum. We previously reported that intracerebroventricular (i.c.v.) administration of PD showed an antinociceptive effect as measured by the tail-flick assay. However, its exact role in the regulation of antinociception in the various types of pain models has not yet been characterized. Thus, we attempted to find antinociceptive profiles of PD in various pain models. PD administered intraperitoneally (i.p.), i.c.v. or intrathecally (i.t.) showed antinociceptive effects in dose-dependent manners as measured by the tail-flick, writhing and formalin tests. In the tail-flick test, PD at the low doses reached the peak after 15 minutes and returned to the control level after 60 minutes. However, higher doses of PD showed a strong antinociception at least for 1 hour. PD administered i.t. showed stronger antinociception than that induced by i.c.v. administration PD in both tail-flick and writhing tests. In the formalin test, PD administered i.p., i.c.v. or i.t. showed antinociceptive effects during both the first (direct nociceptive stimulation) and second (late inflammatory) phases. Pretreatment with naltrexone i.p., i.c.v. or i.t. did not affect PD-induced inhibition of the tail-flick response. Our results suggest that PD shows a strong antinociceptive effect on the tail-flick, writhing and formalin tests, acting on central nervous system. However, PD-induced antinociception may not be mediated by the opioid receptors.

Animals↗

PubMed1981

Screening of the wormicidal Chinese raw drugs on Clonorchis sinensis.

The wormicidal effect on Clonorchis sinensis in boiled water extracts of 223 species (vegetable origin 206, animal origin 10, mineral origin 7) of raw drugs prescribed in Oriental medicine was observed in vitro. The wormicidal substances were detected from 31 of the above-mentioned species. The wormicidal substances extracted from Platycodon grandiflorum (radix), Schizandra chinensis (fruit), Polygala tenuifolia (herb) and Aster tataricus (radix) were most effective. Those from Smilax glabra (radix), Pueraria thunbergiana (flower, radix), Polygala tenuifolia (radix), Scutellaria baicalensis (radix), Prunus mume (fruit), Glycyrrhiza uralensis (radix), Angelica koreana (radix), Phytolacca esculenta (radix) and Cyrtomium fortunei (rhizoma) were effective. The rest of the raw drugs were less effective.

Animals↗

PubMed2004

Chloroplast DNA rearrangements in Campanulaceae: phylogenetic utility of highly rearranged genomes.

BACKGROUND: The Campanulaceae (the "hare bell" or "bellflower" family) is a derived angiosperm family comprised of about 600 species treated in 35 to 55 genera. Taxonomic treatments vary widely and little phylogenetic work has been done in the family. Gene order in the chloroplast genome usually varies little among vascular plants. However, chloroplast genomes of Campanulaceae represent an exception and phylogenetic analyses solely based on chloroplast rearrangement characters support a reasonably well-resolved tree. RESULTS: Chloroplast DNA physical maps were constructed for eighteen representatives of the family. So many gene order changes have occurred among the genomes that characterizing individual mutational events was not always possible. Therefore, we examined different, novel scoring methods to prepare data matrices for cladistic analysis. These approaches yielded largely congruent results but varied in amounts of resolution and homoplasy. The strongly supported nodes were common to all gene order analyses as well as to parallel analyses based on ITS and rbcL sequence data. The results suggest some interesting and unexpected intrafamilial relationships. For example fifteen of the taxa form a derived clade; whereas the remaining three taxa--Platycodon, Codonopsis, and Cyananthus--form the basal clade. This major subdivision of the family corresponds to the distribution of pollen morphology characteristics but is not compatible with previous taxonomic treatments. CONCLUSIONS: Our use of gene order data in the Campanulaceae provides the most highly resolved phylogeny as yet developed for a plant family using only cpDNA rearrangements. The gene order data showed markedly less homoplasy than sequence data for the same taxa but did not resolve quite as many nodes. The rearrangement characters, though relatively few in number, support robust and meaningful phylogenetic hypotheses and provide new insights into evolutionary relationships within the Campanulaceae.

Campanulaceae↗

PubMed1995

Studies on antiinflammatory effect of Japanese Oriental medicines (kampo medicines) used to treat inflammatory diseases.

This study was carried out to examine the antiinflammatory effect of aqueous extracts of Kakkon-to (K), Kakkon-oren-ogon-to (KO), Kikyo-to (KK), Haino-to (H), Haino-san (HS), Mao-to (M) and Senkinkeimei-san (SK), which have been used for the treatment of stomatitis, tonsillitis, cold and chronic inflammatory diseases, and to elucidate the mode of their effects. Oral administration of K, KO, KK, H, HS, M and SK inhibited dose-dependently the increase of dye leakage induced by acetic acid in mice. Further antiinflammatory study was carried out on KK, H and HS which showed potent inhibition. All three extracts significantly inhibited the carrageenin-induced edema and the cotton pellet-induced granuloma formation. From these results, it is suggested that KK, H and HS may inhibit both the early exudative stage and the late proliferative stage in inflammatory processes. These extracts are comprised of Platycodon root as do other crude drugs, and the root may be partly responsible for the antiinflammatory effects induced.

Acetates↗

PubMed1992

Studies on the conformational aspects of inulin oligomers.

The conformational studies of inulin oligomers from G-F2 to G-F9, which isolated from Platycodon grandiflorum, suggested a plausible conformational change between G-F7 and G-F8 from the trends in their chemical shift patterns and molecular rotation; the oligomers higher than G-F8 would form some secondary conformations more rigid than shorter oligomers. On the other hand, spin-lattice relaxation (T1) studies of the protons proposed through-space interactions of 2- and 4-H's of glucose moiety in G-F5, presumably with some atom(s) of the terminal fructose moiety. This would reflect that the inulin molecule adopts a 5/1 helix.

Carbohydrate Conformation↗

PubMed1992

[Studies on the medicinal plant in the "Sambutsu-cho" of Bungo Province possessed by the Kumamoto Clan (II); studies on the medicinal herbs].

In the previous report, I studied the medicinal trees contained in the Sambutsu-cho of the Kumamoto clan in Bungo Province. In this report, I studied the medicinal herbs contained in the same book. There were 259 names in the herbal part. I identified 156 species and found 103 species as the medicinal plants. The ratio of the medicinal plants was 66%. The famous medicinal plants were as follows: Atractilodes japonica, Platycodon gradiflorum, Mentha arvensis var. piperascens, Lisospermum erythrorizon, Pharbitis nil, Gentiana scabra var. buergeri, Cnidium officianal, Angelica acutiloba, Bupleurum falcatum, Pueraria lobata, Paeonia lactiflora, Paeonia suffruticosa, Achyranthes fauriei, Asarum dimidiatum, Ophiopogon japonica, Pinellia ternata and Cyperus rotundus.

Botany↗

PubMed1993

[Studies on the medicinal plant in the "Sambutsu-cho" of Higo Province possessed by the Kumamoto clan (II): on the medicina herbs].

In the previous report, I studied the medicinal trees contained in the Sambutsu-cho of the Kumamoto clan in Higo Province. In this report, I studied the medicinal herbs contained in the same book. There were 439 names in the herbal part. I identified 214 species and found 129 species as the medicinal plants. The ratio of the medicinal plants was 60%. the famous medicinal plants were as follows: Atractilodes japonica, platycodon grandiflorum, prunella vulgaris var. lilacina, pharbitis nil, cnidium officinale, angelica acutiloba, bplerum falcatum, pueraria lobata, sophora flavescens, sinomenium acutum, akebia quinata, paeonia lactiflora, paeonia suffruticosa, achyranthes fauriei, houttuynia cordata, ophiopogon japonica, pinellia ternata and cyperus rotundus.

Botany↗

PubMed1992

[Thin layer chromatography for identification of 9 species of traditional Chinese medicine in baihe gujin tang granules].

Baihe Gujin Tang granules are mainly composed of nine species of traditional Chinese medicine and other admixtures, so the composition is very complex. In order to confirm the presence of each traditional Chinese medicine in the preparation, a thin layer chromatographic method was developed successfully for analysis of Scrophulariae, Platycodon, Paeoniae and Glycyrrhizae.

Chromatography, Thin Layer↗

PubMed2005

[Determination of organochlorine pesticide residues in nine herbs by solid-phase extraction and capillary gas chromatography].

The solid-phase extraction and capillary gas chromatography was introduced for determining 13 organochlorine pesticide residues including alpha-benzene hexachloride (BHC), betaBHC, gamma-BHC, delta-BHC, p,p'-dichloro-diphenyl-dichloroethylene (pp'-DDE), p,p'-dichloro-di-phenyl-dichloroethane (pp'-DDD), o,p'-dichloro-diphenyl-trichloroethane (op'-DDT), pp'-DDT, heptachlor (HEPT), aldrin, heptachlor epoxide (HCE), dieldrin and endrin in Scutellaria baicalensis, Salvia miltiorrhiza, Belamcanda chinensis, Paeoniae lactiflora, Angelica dahurica, Arisaema erubescens, Fructus arctii, Anemarrhena asphodeloides and Platycodon grandiflorum. The organochlorine pesticides were extracted from herbs with mixed solvents of acetone and n-hexane by ultrasonic and cleaned up by Florisil solid-phase extraction column. Then, the extract was separated by capillary column (30 m x 0.25 mm i.d. x 0.25 microm) and detected by electrochemical detector. The carrier gas was N2 (99.999%) with the flow rate of 1.4 mL/min. The split ratio was 1:2.2. The injector temperature was 220 degrees C and the detector temperature was 330 degrees C. The column temperature was increased by the rate of 20 degrees C/min from 100 degrees C to 190 degrees C (hold for 1. 0 min), then to 235 degrees C by the rate of 4 degrees C/min and hold for 7 min at 235 degrees C. The good linearities were obtained for 13 organochlorine pesticides. The detection limits were between 0.064-0.61 microg/L. The average recoveries were between 87.3%-102.3% and relative standard deviations of 1.3%-6.8%. The method is effective, fast and accurate.

Capillary Electrochromatography↗

PubMed2006

[Inhibitory effects of natural plant extracts on Verticillium albo-atrum].

This paper studied the inhibitory effects of 54 kinds of ethanol-extracted plant solutions on Verticillium albo-atrum. The results showed that 15 kinds of these extracts could inhibit the growth of verticillium albo-atrum mycelium, with an inhibitory rate more than 50%, among which, the inhibitory rate of Asarum sieboldii, Coptis chinensis, Magnolia officinalis, Acacia catechu, Sophora flavescens, Glycyrrhiza uralensis, Cnidium monnieri, Platycodon grandiflorum and Allium. cepa. extracts was higher than 65%, and that of Cnidium monnieri extract reached 86.84%. A total of 16 kinds of plant extracts decreased the spore germination of V. albo-atrum, with the inhibitory rate higher than 70%, and there were 7 kinds of plant extracts whose inhibitory rate reached 95%. Almost no spore bourgeon was found after treated with Asarum sieboldii, Coptis chinensis, and Magnolia officinalis extracts. The extract of Acacia catechu did not inhibit the growth of mycelium, but restrained the spore germination by 100%. Cnidium monnieri extract could strongly inhibit the growth of mycelium, but had a less effect on spore germination rate (only by 11.3%). The active substances found in natural plant extracts which had the inhibitory effects on pathogen brought us a new and promising method to deal with V. albo-atrum and other vegetable diseases.

Anti-Bacterial Agents↗

PubMed1991

A study on the mutagenicity of 102 raw pharmaceuticals used in Chinese traditional medicine.

The mutagenic potential of traditional Chinese drugs was studied. After extraction with boiling water and frozen vacuum drying, preparations from 102 raw drugs were tested with the Ames test, and the micronucleus and chromosomal aberration assays in mice in vivo. Astragalus mongholicus Bunge (+S9), Sophora japonica L. (+/- S9) and Eucommia ulmoides Oliv. (+/- S9) were found to significantly induce His+ revertants in Salmonella typhimurium TA98 and/or TA100. Besides these 3, 10 other extracts were positive in the chromosomal aberration and micronucleus assays in mice. They are Datura metal L., Artemisia capillaris Thunb., Carthamus tinctorius L., Forsythia suspensa Thumb., Rehmannia glutinosa f. Hueichingensis (fermented), Paeonia suffruticosa Andr., Platycodon grandiflorum Jacq. DC., Cinnamomum mairei Levl., Notopterygium incisium Ting., and Sophora flavescens Ait. The relevance of these findings is discussed.

Animals↗

PubMed2004

Determination of the kinetic properties of platycodin D for the inhibition of pancreatic lipase using a 1,2-diglyceride-based colorimetric assay.

A 1,2-diglyceride-based multi-step colorimetric assay to measure the pancreatic lipase activity was applied for the determination of the kinetic profiles of the lipase inhibition with a slight modification and the validity verification. With this assay method, our study revealed that platycodin D, one of major constituents of Platycodi Radix, inhibits the pancreatic lipase activity in a competitive type, with the value of KI being 0.18+/-0.02 mM. In addition, PD has affected the values of K(m,app) and Kcat/Km in a dose-dependent manner. The results shed a meaningful light on how PD mediates lipid metabolism in the intestinal tracts. On the other hand, since the revised assay is sensitive, rapid, and does not affect the accuracy to the kinetic properties, it is applicable not only to evaluation of the kinetic properties of the pancreatic lipase, but also to high-throughput screening of pancreatic lipase activity.

Colorimetry↗

PubMed2005

In vitro inhibitory effect of triterpenoidal saponins from Platycodi Radix on pancreatic lipase.

In the process of investigating anti-obesity effect of Platycodi Radix, we found that aqueous extract of Platycodi Radix might inhibit intestinal absorption of dietary fat by inhibiting pancreatic lipase (PL) activity. In order to clarify the anti-obesity mechanism of Platycodi Radix, activity-guided isolation was performed to find active components. The total saponin fraction of Platycodi Radix appeared to have a potent inhibitory activity against the hydrolysis of triolein emulsified with phosphatidycholine by pancreatic lipase in vitro. Based on these results, further purification of active components yielded 10 known triterpenoidal saponins, among these compounds, platycodin A, C, D, and deapioplatycodin D exhibited significant inhibitory effects on PL at the concentration of 500 microg/mL with 3.3, 5.2, 34.8, and 11.67% pancreatic lipase activity vs control, respectively. Platycodin D was found to inhibit the PL activity in a dose-dependent manner. Therefore, the anti-obesity effect of Platycodi Radix might be due to the inhibition of pancreatic lipase by its saponins.

Anti-Obesity Agents↗