Triterpenoid Aglycones Research Articles

Mass spectrometry as a tool for the dereplication of saponins from Ampelozizyphus amazonicus Ducke bark and wood.

Mass spectrometry in natural products research has been used as a first step to identify possible chemical structures and to guide subsequent efforts to isolate novel compounds. Preparations of Ampelozizyphus amazonicus Ducke (AA) are known for their high content of saponins, especially dammarane-type triterpenoid aglycones. In the Amazon, where it is known as "saracura-mirá", roots and bark are widely used for the treatment and prevention of malaria, while the wood is discarded. The extract prepared from the wood is also saponin-rich, but its exact chemical composition has not been described. This study provides information on the chemical profiling and tentative structural identification of the major compounds (saponins) present in aqueous and ethanol extracts of bark and wood of AA by mass spectrometry. The strategy used to identify compounds present in all samples was ultra-high-performance liquid chromatography with an ultraviolet detector coupled to tandem mass spectrometry (UHPLC-UV-MS/MS) for the analysis of fragmentation patterns through product ion scan using MZmine 2 software. Also, direct sample injection and electrospray ionisation combined with high-resolution mass spectrometry (DI-ESI-HRMS) measurements were performed. The extracts showed chemical similarity, and 95 saponins were tentatively identified in AA wood and bark, including 73 which are described for the first time as tentative structures for this plant species. This research describes a useful method for the fast and simultaneous tentative identification of major saponins in AA, contributing to the study of the chemical properties of this genus and family. Furthermore, it demonstrates the importance of the qualitative dereplication process, allowing a straightforward way to propose the tentative identification of compounds.

Abstract A58: HR-ESI-MS identification of novel triterpenoid antitumor substances in securidaca 1, using activity-guided SRB assay

Abstract Background: Securidaca 1 is a triterpenoid saponin fraction obtained from African medicinal plant S. longipedunculata, whose action activated apoptosis via inhibition of PI3K-AKT downstream. Preliminary studies show an IC50 of 7.03 (μg/mL), with RT-qPCR gene expression revealing a fold-change reduction of MCL-1 and BCL2L1 antiapoptotic proteins, as well as the inhibition of AKT-3, VEGFA, and CDH-1. Therefore, considering the role of PI3K-AKT pathway in tumoral resistance of ovarian cancer and epithelial-mesenchymal transition during development, our major aim was to isolate and identify the components of securidaca 1 responsible for the activity. Experimental Procedure: Freeze-dried sample of securidaca 1 was fractionated by FLASH chromatography (RP-C18) and the resultant fractions screened by SRB cytotoxicity assay (96-well format) using HeLa cell line. The most promising subfraction was further purified by semipreparative HPLC (reversed-phase). Isolated substances were identified by HR-ESI-MS and IC50s determined and compared with 5-fluorouracil (5-FU) reference standard. Results: The HR-ESI-MS spectrum under negative ion mode revealed the parent molecular ion peaks of the semipreparative fractions (FR15-6 and FR15-7), whose IC50s were confirmed at 3.84 and 4.83 μg/mL, respectively, on HeLa cell line, more sensitive than 5-FU. MS/MS fragmentation spectra (negative ion mode) show putative fragments of molecular ions 455 and 425 (m/z), respectively, typically indicating oleanine triterpenoid aglycone. Post-TLC derivatization tested positive to Liebermann Burckhard and Carr Price reactions, and sugars. Conclusion: FR15-6 and FR15-7 are potential candidates for anticancer development whose actions may be responsible for antitumor activities previously seen in securidaca 1. Work is ongoing to evaluate their capacities in blocking tumor development via antiapoptotic effectors of PI3K-AKT downstream pathway. Note: This abstract was not presented at the conference. Citation Format: Titus Chukwuemeka Obasi, Radu Oprean. HR-ESI-MS identification of novel triterpenoid antitumor substances in securidaca 1, using activity-guided SRB assay [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A58.

Advances on hormone-like activity of Panax ginseng and ginsenosides.

Traditional Chinese medicine (TCM) has been paid much attentions due to the prevention and treatment of steroid hormone disorders. Ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae), is one of the most valuable herbs in complementary and alternative medicines around the world. A series of dammarane triterpenoid saponins, also known as phytosteroids, were reported as the primary ingredients of Ginseng, and indicated broad spectral pharmacological actions, including anti-cancer, anti-inflammation and anti-fatigue. The skeletons of the dammarane triterpenoid aglycone are structurally similar to the steroid hormones. Both in vitro and in vivo studies showed that Ginseng and its active ingredients have beneficial hormone-like role in hormonal disorders. This review thus summarizes the structural similarities between hormones and dammarane ginsenosides and integrates the analogous effect of Ginseng and ginsenosides on prevention and treatment of hormonal disorders published in recent twenty years (1998-2018). The review may provide convenience for anticipate structure-function relationship between saponins structure and hormone-like effect.

Advances in biosynthesis of triterpenoid saponins in medicinal plants.

In recent years, biosynthesis of triterpenoid saponins in medicinal plants has been widely studied because of their active ingredients with diverse pharmacological activities. Various oxidosqualene cyclases, cytochrome P450 monooxygenases, uridine diphosphate glucuronosyltransferases, and transcription factors related to triterpenoid saponins biosynthesis have been explored and identified. In the biosynthesis of triterpenoid saponins, the progress of gene mining by omics-based sequencing, gene screening, gene function verification, catalyzing mechanism of key enzymes and gene regulation are summarized and discussed. By the progress of the biosynthesis pathway of triterpenoid saponins, the large-scale production of some triterpenoid saponins and aglycones has been achieved through plant tissue culture, transgenic plants and engineered yeast cells. However, the complex biosynthetic pathway and structural diversity limit the biosynthesis of triterpenoid saponins in different system. Special focus can further be placed on the systematic botany information of medicinal plants obtained from omics large dataset, and triterpenoid saponins produced by synthetic biology strategies, gene mutations and gene editing technology.

A Seed-Specific Regulator of Triterpene Saponin Biosynthesis in Medicago truncatula.

Plants produce a vast array of defense compounds to protect themselves from pathogen attack or herbivore predation. Saponins are a specific class of defense compounds comprising bioactive glycosides with a steroidal or triterpenoid aglycone backbone. The model legume Medicago truncatula synthesizes two types of saponins, hemolytic saponins and nonhemolytic soyasaponins, which accumulate as specific blends in different plant organs. Here, we report the identification of the seed-specific transcription factor TRITERPENE SAPONIN ACTIVATION REGULATOR3 (TSAR3), which controls hemolytic saponin biosynthesis in developing M. truncatula seeds. Analysis of genes that are coexpressed with TSAR3 in transcriptome data sets from developing M. truncatula seeds led to the identification of CYP88A13, a cytochrome P450 that catalyzes the C-16α hydroxylation of medicagenic acid toward zanhic acid, the final oxidation step of the hemolytic saponin biosynthesis branch in M. truncatula In addition, two uridine diphosphate glycosyltransferases, UGT73F18 and UGT73F19, which glucosylate hemolytic sapogenins at the C-3 position, were identified. The genes encoding the identified biosynthetic enzymes are present in clusters of duplicated genes in the M. truncatula genome. This appears to be a common theme among saponin biosynthesis genes, especially glycosyltransferases, and may be the driving force of the metabolic evolution of saponins.

Simultaneous determination of various platycosides in Four Platycodon grandiflorum cultivars by UPLC-QTOF/MS

In Platycodi Radix (root of Platycodon grandiflorum), there are a number of platycosides that consist of a pentacyclic triterpenoid aglycone and two sugar moieties. Due to the pharmacological activities of platycosides, it is critical to assess their contents in PR, and develop an effective method to profile various platycosides is required. In this study, an analytical method based on ultra performance liquid chromatography coupled with quadrupole time-of-flight/mass spectrometry (UPLC-QTOF/MS) with an in-house library was developed and applied to profile various platycosides from four different Platycodi Radix cultivars. As a result, platycosides, including six isomeric pairs, were successfully analyzed in the PRs. In the principal component analysis, several platycosides were represented as main variables to differentiate the four Platycodi Radix cultivars. Their different levels of platycosides were also represented by relative quantification. Finally, this study indicated the proposed method based on the UPLC-QTOF/MS can be an effective tool for identifying the detail characterization of various platycosides in the Platycodi Radix.

Identification of oxidosqualene cyclases from the medicinal legume tree Bauhinia forficata: a step toward discovering preponderant α-amyrin-producing activity.

Triterpenoids are widely distributed among plants of the legume family. However, most studies have focused on triterpenoids and their biosynthetic enzymes in model legumes. We evaluated the triterpenoid aglycones profile of the medicinal legume tree Bauhinia forficata by gas chromatography-mass spectrometry. Through transcriptome analyses, homology-based cloning, and heterologous expression, we discovered four oxidosqualene cyclases (OSCs) which are responsible for the diversity of triterpenols in B.forficata. We also investigated the effects of the unique motif TLCYCR on α-amyrin synthase activity. B.forficata highly accumulated α-amyrin. We discovered an OSC with a preponderant α-amyrin-producing activity, which accounted for at least 95% of the total triterpenols. We also discovered three other functional OSCs (BfOSC1, BfOSC2, and BfOSC4) that produce β-amyrin, germanicol, and cycloartenol. Furthermore, by replacing the unique motif TLCYCR from BfOSC3 with the MWCYCR motif, we altered the function of BfOSC3 such that it no longer produced α-amyrin. Our results provide new insights into OSC cyclization, which is responsible for the diversity of triterpenoid metabolites in B.forficata, a non-model legume plant.

Differences in Neuritogenic Activity and Signaling Activation of Madecassoside, Asiaticoside, and Their Aglycones in Neuro-2a cells.

Madecassoside (MS) and asiaticoside (AS) along with their aglycones, madecassic acid (MA) and asiatic acid (AA), are considered the major neuroactive triterpenoid constituents of Centella asiatica. In this study, we aimed to compare MS, AS, MA, and AA for their neurite outgrowth activities and mechanisms in Neuro-2a cells. Immunofluorescent cell staining showed MS and AS significantly increased the percentage of neurite-bearing cells (%NBC) and the neurite length with higher potency than MA and AA. The triterpenoid glycosides induced sustained extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation, while their aglycones activated only transient signaling of ERK1/2. Suppression of ERK1/2 activation significantly abolished not only cAMP response element-binding protein (CREB) phosphorylation but also the increment of %NBC and neurite length in MS- and AS-treated cells. Inhibition of ERK phosphorylation did not produce similar blockage of CREB activation and neurite outgrowth in MA- and AA-treated cells. On the other hand, inactivation of protein kinase B (Akt) resulted in a suppression of neurite lengthening in all studied triterpenoids. This is the first study discerning the different signaling pathways of neurite outgrowth activity induced by C. asiatica triterpenoid glycosides and aglycones. Neurite outgrowth activity of the glycosides MS and AS was found to involve the activation of sustained ERK phosphorylation leading to CREB activation, while ERK activation was not associated with MA- and AA-induced neurite outgrowth. In addition, Akt activation was evident to be more involved in neurite elongation process.

Genotype- and provenance-related variation in the leaf surface secondary metabolites of silver birch

The cuticular wax layer on silver birch (Betula pendula Roth) leaves is rich in cyclic secondary metabolites that provide defense against various environmental factors. Micropropagated trees from the southern (60°N), central (62°N), and northern (66°N) latitudes of Finland were grown in a common garden setup and quantified for variation in leaf surface secondary metabolites and other leaf traits, and their association with genotype and provenance was studied. The 12 genotypes studied differed greatly in the quantity of surface secondary metabolites, both for individual flavonoid and triterpenoid aglycones and for the overall metabolite profile. Qualitative differences were observed for one triterpenoid that was present in a single genotype (R3). The variance explained by the provenance was low (between 1% and 36%) for most metabolites, but the profile showed clear separation by provenance. The contents of two alkyl coumarates, reported for the first time in silver birch leaf waxes, displayed differences a...

Pentacyclic triterpenoids from Cyclocarya paliurus and their antioxidant activities in FFA-induced HepG2 steatosis cells

Six undescribed pentacyclic triterpenoids including four triterpenoid aglycones, 1β,2a,3β,23-tetrahydroxyurs-12-en-28-ursolic acid, 2a,3a,6β,19α,23-pentahydroxyurs-12-en-28-ursolic acid, 2α,3α,20β,23-tetrahydroxyurs-12-en-28-ursolic acid and 1β,2a,3β,23-tetrahydroxyurs-12,20(30)-dien-28-ursolic acid, and two triterpenoid glucosides, 2a,3a,23-trihydroxy-12,20(30)-dien-28-ursolic acid 28-O-β-d-glucopyranoside and 1-oxo-3β,23-dihydroxyolean-12-en-28-oic acid 28-O-β-d-xylopyranoside, along with 5 known triterpenoids were isolated from a CH3Cl-soluble extract of the leaves of Cyclocarya paliurus. Their structures were established on the basis of chemical and spectroscopic approaches. These compounds were assessed for their antioxidant effects on FFA-induced hepatic steatosis in HepG2 cells. The results revealed that three saponins and two aglycones markedly increased SOD activity and reduced MDA level.

LC–MSn characterization of saponins in mate (Ilex paraguariens, St. Hil) and their quantification by HPLC-DAD

Saponins are secondary plant metabolites constituted by a triterpenoid aglycone with one or more sugar chains. There is increasing interest in saponins due to their potential health effects. Yerba mate is an important source of saponins in many South American diets. The aim of this study was to develop a one-step procedure to isolate saponins from yerba mate, followed by their characterization by liquid chromatography/tandem high-resolution mass spectrometry (LC-ESI–MS) and quantification by high performance liquid chromatography-diode array (HPLC-DAD). Methanol extraction proved to be a highly effective method to extract yerba mate saponins. LC/MSn analysis allowed identifying three free triterpenes and 16 saponins of which five were identified for the first time. HPLC-DAD results revealed that ursolic acid was the main free aglycone (1.557–1.807mg/g vs. 0.229–0.294mg/g oleanolic acid and 0.024–0.036mg/g hydroxylated aglycone). Saponin contents varied from 4.4 to 5.5mg/g in four commercial brands, being matesaponin D or J3a the most abundant.

Triterpenoids from Cyclocarya paliurus and their inhibitory effect on the secretion of apoliprotein B48 in Caco-2 cells

Five previously undescribed compounds including two triterpenoid aglycones, 3β,23-dihydroxy-1,12-dioxo-olean-28-oic acid and 3β,23,27-trihydroxy-1-oxo-olean-12-ene-28-oic acid, and three triterpenoid glucosides cyclocarioside L-N, along with 17 known compounds were isolated from a CH3Cl-soluble extract of the leaves of Cyclocarya paliurus. Two 27-nor-triterpenoid glycosides were isolated from the genus for the first time. Furthermore, the characterized compounds were tested for the inhibitory effects on apoliprotein B48 secretion in Caco-2 cells. Seven triterpenoid aglycones together with four triterpenoid saponins significantly decreased the apoliprotein B48 oversecretion induced by oleic acid in Caco-2 cells.

An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents.

Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity.

Low vapor pressure deficit reduces glandular trichome density and modifies the chemical composition of cuticular waxes in silver birch leaves.

Cuticular wax layer is the first barrier against the outside environment and the first defense encountered by herbivores and pathogens. The effects of environmental factors on cuticular chemistry, and on the formation of glandular trichomes that account for the storage and secretion of lipophilic compounds to the leaf surface are poorly understood. Low vapor pressure deficit (VPD) has shown to reduce the nitrogen (N) status of plants. Thus, we studied the effects of elevated air humidity, indicated as VPD, and the effect of N fertilization on cuticular waxes and glandular trichome density in silver birch (Betula pendula Roth). Experiments were carried out in growth chambers with juvenile plants and in a long-term field experiment with older trees. Low VPD reduced the glandular trichome density in both experiments, in chamber and in field. The contents of the major triterpenoid and flavonoid aglycones correlated positively with glandular trichome density, which supports the role of trichomes in the exudation of secondary compounds to the leaf surface. A closer examination of the cuticular wax chemistry in the chamber experiment revealed that low VPD and N supply affected the composition of cuticular waxes, but not the total wax content. The deposition of different wax compounds followed a co-ordinated pattern in birch leaves, but different compound groups varied in their responses to N fertilization and low VPD. Low VPD reduced the hydrophobicity of cuticular waxes, as demonstrated by lower alkane content and less hydrophobic flavonoid profile in low VPD than in high VPD. Reduced hydrophobicity of the wax layer is presumed to increase leaf wettability. Together with reduced trichome density in low VPD it may enhance the susceptibility of trees to fungal pathogens and herbivores. High N supply under low VPD reduced the effect of low VPD on the cuticular wax composition. Total fatty acid content and the expression of β-amyrin synthase were lower under high N supply than under moderate N supply irrespective of VPD treatment. Nitrogen availability and decreasing VPD will modify leaf surface properties in silver birch and thereby affect tree defence against abiotic and biotic stress factors that emerge under climate change.

Saponins from Chinese Medicines as Anticancer Agents.

Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins) and steroid saponins (dioscin, polyphyllin, and timosaponin) isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.

Surface properties of adsorption layers formed from triterpenoid and steroid saponins

Abstract Saponins are natural surfactants with non-trivial surface and aggregation properties which find numerous important applications in several areas (food, pharma, cosmetic and others). In the current paper we study the surface properties of ten saponin extracts, having different molecular structure with respect to the type of their hydrophobic fragment (triterpenoid or steroid aglycone) and the number of sugar chains (1 to 3). We found that the triterpenoid saponins Escin, Tea Saponin and Ginsenosides have area per molecule in the range between 0.5 and 0.7 nm2, and the adsorbed molecules are orientated perpendicularly to the interface. The comparison of the experimentally measured surface elasticities with theoretically estimated ones shows that the saponins with very high dilatational and shear elasticities (up to 2000 mN/m) have molecular interaction parameter in the adsorption layers which is above the threshold value for two-dimensional phase transition. In other words, the highly elastic layers are in surface condensed state, due to strong attraction between the adsorbed molecules. Furthermore, these adsorption layers have non-linear rheological response upon expansion and contraction, even at relatively small deformation. Layers from the other studied saponins (steroids and crude mixtures of triterpenoid saponins), which are unable to form strong intermolecular bonds within the adsorption layer, have zero shear elasticity and viscosity and low dilatational elasticity and viscosity, comparable in magnitude to those reported in literature for protein adsorption layers. The comparison of the results, obtained by several independent experimental methods, allowed us to formulate the conditions under which the results from different interfacial rheology tests could be compared, despite the complex non-linear response of the saponin adsorption layers.

Triterpenoid saponins from the aerial parts of Trifolium argutum Sol. and their phytotoxic evaluation

Four triterpenoid saponins (1–4) were isolated from the aerial parts of Trifolium argutum Sol. (sharp-tooth clover) and their structures were elucidated by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and chemical methods. Two of them are new compounds, characterized as 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,24-dihydroxyolean-12-ene-22-oxo-29-oic acid (1) and 3-O-[β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,24-dihydroxyolean-12-ene-22-oxo-29-oic acid (2). The occurrence of 3β,24-dihydroxyolean-12-ene-22-oxo-29-oic acid (melilotigenin) in its natural form is reported for the first time as a triterpenoid aglycone within Trifolium species. The phytotoxicity of compounds was evaluated on four STS at concentration 1μM to 333μM. Compound 1 was the most active, showing more than 60% inhibition on the root growth of L. sativa at the higher dose, with IC50 (254.1μM) lower than that of Logran® (492.6μM), a commercial herbicide used as positive control. The structure–activity relationships indicated that both aglycones and glycosidic parts may influence the phytotoxicity of saponins.

P450s and UGTs: Key Players in the Structural Diversity of Triterpenoid Saponins

The recent spread of next-generation sequencing techniques has facilitated transcriptome analyses of non-model plants. As a result, many of the genes encoding enzymes related to the production of specialized metabolites have been identified. Compounds derived from 2,3-oxidosqualene (the common precursor of sterols, steroids and triterpenoids), a linear compound of 30 carbon atoms produced through the mevalonate pathway, are called triterpenes. These include essential sterols, which are structural components of biomembranes; steroids such as the plant hormones, brassinolides and the toxin in potatoes, solanine; as well as the structurally diverse triterpenoids. Triterpenoids containing one or more sugar moieties attached to triterpenoid aglycones are called triterpenoid saponins. Triterpenoid saponins have been shown to have various medicinal properties, such as anti-inflammatory, anticancerogenic and antiviral effects. This review summarizes the recent progress in gene discovery and elucidates the biochemical functions of biosynthetic enzymes in triterpenoid saponin biosynthesis. Special focus is placed on key players in generating the structural diversity of triterpenoid saponins, cytochrome P450 monooxygenases (P450s) and the UDP-dependent glycosyltransferases (UGTs). Perspectives on further gene discovery and the use of biosynthetic genes for the microbial production of plant-derived triterpenoid saponins are also discussed.

Chemical constituents from Polygonatum odoratum

Twenty-two compounds, including five homoisoflavanones (1–3, 7 and 8), three isoflavones (9–11), flavone glycoside (19), one triterpenoid aglycon (5), two steroidal sapogenins (4, 6), five steroidal saponins (12, 13, 20–22), three lignanoids (14, 17 and 18) and two fatty acids (15 and 16) were isolated from the rhizomes of Polygonatum odoratum. The structures were elucidated by spectroscopic methods and by comparison of the reported spectral data. Additionally, the relationships between this plant and other species from Liliaceae family have also been discussed on the basis of the given compounds.

도라지의 생산과 가공 향상에 관한 최신 연구 동향

Balloon flower (BF, Platycodon grandiflorum (Jacq.) A.DC.) is a monotypic species of the bellflower family (Campanulaceae), which is native to Asia. In terms of popular culture of east asian country, BF has been in the limelight as flowers, medicine and food. Platycosides (saponins) from the roots of BF are reported to have a wide range of efficacy and characterized by a structure containing a triterpenoid aglycone and two sugar chains. Saponins from BF are of pharmaceutical significance, and their applications are increasing with evidence of their efficacy. As the cultivation area of BF is continually increased in Korea, research for preventing root rot incidence and nitogen fertilizer application on yield of saponin are reported and also storaging, steam heating and bio-transformational method are developed. There are several biological effects of compounds from BF. saponin from BF has cholesterol lowering effects, neuroprotective activity, cytotoxic effects against cancer cells, and polysaccharide has immuno-boosting effects and pheolic compounds from aerial part of BF has anti-oxidative effects. However, The purchase decision factor of consumers in market is cultivate year of BF and producing country are also important as contents of platycodins in BF. This paper reviews the origin of plants, harvest and post harvest processing methods that maximize the value in terms of efficacy of extracts and platicoside from BF. Keywords: Biological effect, Platycodon grandiflorum, Platycoside, Saponin