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There are 176 endemic plants spread in southern Colchis, of which 45 can be used for some medical treatments. The bioecology and detailed phytochemical content of some medicinal plant populations have not been studied so far. The research objectiveis to study the phytochemical content of endemic species of Helleborus caucasicus, Helleborus abchasicus and Ficaria popovii spread in southern Colchis. The research method for the phytochemical content included separation analysis, whichwas performed byusing UPLC-MS (Waters Acquity QDa detector). Three Steroidal glycosideswere isolated from the MeOH extract of the plants of Helleborus caucasicus and Helleborus abchasicus: Hellebrigenin-D-glucose, 20 – Hydroxyecdysone and Hydroxyecdysone – 3 glucoside. Two saponins (Hederagenin 3-O -α-L-arabino pyranoside, Hederagenin28-O-[α-L-rhamno-pyranosyl(1→4)-β-D-glucopyranosyl-(1→6)]β-D-lucopyranoside) and four flavonoids (kaempferol 3-O-β-ᴅ- (6ʺ-α-ʟ-rhamnopyranosyl)-glucopyranoside (nicotiflorin), apigenin 8-C-β-ᴅ-glucopyranoside (vitexin), luteolin 8-C-β-ᴅ-glucopyranoside (orientin), quercetin 3-O-rutinoside) were isolated from the tubers and flowers of Ficaria Popovii. Three Steroidal glycosides and Hydroxyecdysone -3 glucoside were isolated from the MeOH extract of Helleborus caucasicus.In addition, two saponins and four flavonoids were isolated from the tubers and leaves of FicariaPopovii.

Gypsogenin (1) and hederagenin (2) were isolated by extracting the powdered roots of Saponaria officinalis and the pericarp of Sapindus saponaria, respectively. While the gypsophila derived saponin can be obtained easily and in large quantities as a technical product, the plant material from Sapindus saponaria is difficult to obtain in Europe and the North-Americas, whereas in Latin America it is readily available (unlike the gypsophila saponin). In order to achieve a better accessibility of both aglycones, gypsogenin (1) and hederagenin (2), a simple synthesis for their interconversion was developed. Modification of the reaction conditions led to the first synthesis of 4-epi-hedragonic acid (3).

Background. Hederagenin is one of the main components of Tetrapanax papyriferus, and Tetrapanax papyriferus is one of the ingredients of Danggui Sini decoction. To explore whether Tetrapanax papyriferus and hederagenin can alleviate mechanical pain, thermal hyperalgesia, and cold pain at the same time, we comprehensively investigated the effects of two drugs on the levels of p38 MAPK phosphorylation, TRP proteins, and IL1β, IL6, and TNF-α in serum. Methods. Firstly, we obtained pain-related targets and performed KEGG pathway enrichment on these targets. Then, 42 SD rats were separated randomly into six groups: sham operation group, CCI group, pregabalin group, mecobalamin group, Tetrapanax papyriferus group, and hederagenin group. All drugs were given orally. Rats in the sham operation group and CCI group were gavaged with saline. Rats in the pregabalin group were given pregabalin, while rats in the mecobalamin group were given mecobalamin. Rats in the Tetrapanax papyriferus group were given Tetrapanax papyriferus, while rats in the hederagenin group were given hederagenin. Besides, we conducted behavioral tests including acetone test, hot plate experiment, and von Frey filaments, and then dorsal root ganglion neurons were taken out on the 21st day after operation. Then, western blot, ELISA, and hematoxylin-eosin staining were conducted. Results. Rats in the CCI group were more sensitive to hyperalgesia and allodynia to mechanical and thermal stimuli, as well as cold pain. All four drugs could relieve these pains. Pregabalin, mecobalamin, and Tetrapanax papyriferus can reduce the levels of IL1β, IL6, and TNF-α in serum compared to those of the CCI group. The expression of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in DRG increased evidently on the 21st day after the operation in the CCI group. All four drugs could reduce the expressions of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in dorsal root ganglion compared to those of the CCI group. Conclusion. Tetrapanax papyriferus and hederagenin relieved sciatica by reducing inflammation levels, inhibiting p38 MAPK phosphorylation, and decreasing the levels of dorsal root ganglion proteins.

Hit anti-leishmanial saponin structures selected following primary and secondary screening., Leishmaniasis is a neglected tropical disease caused by insect-vector borne protozoan parasites of the, Leishmania species. Whilst infection threatens and affects millions of the global poor, vaccines are absent and drug therapy limited. Extensive efforts have recently been made to discover new leads from small molecule synthetic compound libraries held by industry; however, the number of new chemical entities identified and entering development as anti-leishmanials has been very low. This has led to increased interest in the possibility of discovering naturally derived compounds with potent antileishmanial activity which may be developed towards clinical applications. Plant-derived triterpenoid and steroidal saponins have long been considered as anti-microbials and here we describe an investigation of a library of 137 natural (9) and semi-synthetic saponins (128) for activity against Leishmania mexicana, a causative agent of cutaneous leishmaniasis. The triterpenoid sapogenin, hederagenin, readily obtained in large quantities from Hedera helix (common ivy), was converted into a range of 128 derivatives. These semi-synthetic compounds, as well as saponins isolated from ivy, were examined with a phenotypic screening approach to identify potent and selective anti-leishmanial hits. This led to the identification of 12 compounds, including the natural saponin gypsogenin, demonstrating high potency (ED50 < 10.5 μM) against axenic L. mexicana amastigotes, the mammalian pathogenic form. One of these, hederagenin disuccinate, was sufficiently non-toxic to the macrophage host cell to facilitate further analyses, selectivity index (SI) > 10. Whilst this was not active in an infected cell model, the anti-leishmanial properties of hederagenin-derivatives have been demonstrated, and the possibility of improving the selectivity of natural hederagenin through chemical modification has been established.

Nine different oleanane-type glycosides were extracted and isolated by various chromatographic methods from two Weigela florida cultivars, “Pink Poppet” and “Jean’s Gold”. From the roots of W. florida “Pink Poppet”, three monodesmosidic oleanolic acid saponins 1, 4, 5 were obtained, together with one hederagenin ester 6 from the leaves, and six bidesmosidic saponins 2, 3, 6-9 were isolated from the leaves of W. florida “Jean’s Gold”. Among compounds 1-9, three were previously undescribed (1-3) and six (4-9) were already published in the literature. Their structures were assigned by spectroscopic analysis mainly 2D NMR and mass spectrometry (ESI-MS). The cytotoxicity of the isolated compounds 1, 3, 4, 6, 7, 9, against mouse colon carcinoma (CT26), mouse melanoma (B16) and human liver cancer (HepG2) cell lines, was evaluated by MTS assay. The ester group at C-28 and/or the primary alcohol function at C-23 led to a negative effect, whereas monodesmosidic oleanolic acid glycosides displayed a good cytotoxicity with IC50 ranging from 2.19 to 2.83 μM. A key sequence in the structure of the molecules was proposed for the cytotoxicity.

Background: Based on the biological significance of hederagenin-type saponins found in our previous investigation, a series of new hederagenin derivatives were designed and synthesized. Methods : Their in vitro antiproliferative activities were evaluated against the HepG2 liver cancer cell line and normal cell line L929 by MTT assay. Results: The preliminary bioassay results demonstrated that all the tested compounds 1-7 showed potent anti-hepatoma activities, and some compounds exhibited better effects than 5-fluorouracil against human hepatocellular carcinoma HepG2 cell line. Furthermore, compound 5 showed a significant antihepatoma activity against HepG2 cells with an IC50 value of 1.88 µM. Besides, all of the tested compounds showed a low cytotoxic effect against the normal cell line L929. Conclusion: All the compounds 1-7 displayed superior selectivity against human hepatocellular carcinoma HepG2 cell line, and the results suggest that the structural modifications of C ring on the hederagenin backbone are vital for modulating anti-hepatoma activities.

The paper reports preparation of molecular complexes of cholesterol with dominant triterpene saponins from members of the ivy genus Hedera L. (Araliaceae Juss.), that is, monodesmosidic glycoside α-hederin (hederagenin 3-O-α-L-rhamnopyranosyl-(1→2)-O-α-L-arabinopyranoside) and bisdesmosidic glycoside hederasaponin C (hederagenin 3-O-α-L-rhamnopyranosyl-(1→2)-O-α-L-arabinopyranosyl-28-О-α-L-rhamnopyranosyl-(1→4)-О-β-D-glucopyranosyl-(1→6)-О-β-D-glucopyranoside), as well as with minor monodesmosidic glycoside hederoside F (hederagenin 3-О-β-D-glucopyranosyl-(1→2)-О-β-D-glucopyranoside). The complexation has been investigated by methods of isomolar series in the spectrophotometric version and FT-IR spectroscopy with a universal optical attenuated total reflection (ATR) accessory. It has been shown that α-hederin, hederasaponin C, and hederoside F form 1 : 1 complexes with cholesterol, having a stability constants (5.6 ± 0.1) × 104, (4.7 ± 0.1) × 104 and (6.0 ± 0.6) × 104 M–1, respectively (in 70% aqueous ethanol at 25°С). The constants are calculated on the basis of isomolar curves. The complexes of cholesterol with ivy monodesmosidic glycosides are more stable. Intermolecular interaction in the complexes is carried out by hydrogen bonds formation of type –С=О⋅⋅⋅Н–О– (for monodesmosidic glycosides) and –(Н)О⋅⋅⋅Н–О– (for bisdesmosidic glycoside). Hydrophobic contacts of the aglycone part of glycosides (hederagenin) with a lipophilic cholesterol molecule are possible. As a result, changes in some frequencies of the absorption bands of CH bonds are observed, which was established by IR-spectroscopy.

A UPLC-MS/MS method was developed and validated the determination and pharmacokinetic study of magnoflorine, cauloside C, hederagenin, and oleanolic acid from Caulophyllum robustum. Digoxin was used as the internal standard. The pretreated plasma samples were carried out on a Waters ACQUITYUPLC HSS T3 column at 35 °C with a mobile phase of acetonitrile-water (90:10, v/v) at a flow rate of 0.2 mL/min. This article describes the most simple, sensitive, and validated UPLC-MS/MS method to date for the simultaneous successful determination of four compounds in rat plasma after oral administration of the extract of C. robustum and their pharmacokinetic studies.

Hederagenin, a saponin known for its therapeutic effect was isolated from leaves of Hedera helix. Hederagenin was obtained by repeated maceration of ground plant material in 95% (v/v) ethanol. The ethanolic extract was subjected to acid hydrolysis and purification with acetonitrile. Isolated hederagenin (IHe) was analyzed by HPLC-MS/MS and compared to standard hederagenin. In vitro cytotoxicity of IHe was tested in a culture of fibroblast cells from NCTC clone L929 cell line by MTT assay, using dioscin as positive control. For the determination of IHe antitumor effect, in vitro tests were performed in a culture of human cervix carcinoma Hep-2 cells cultivated in the presence of different concentrations of sample for 48 h. IHe was biocompatible in the range of concentrations 2-200 mg/mL, in NCTC cell culture. The compound showed cell cytotoxicity in the concentration range of 100-400 mg/mL, in Hep-2 cell culture, revealing its antitumor activity. These results demonstrated the possible use of hederagenin isolated from H. helix extract as an antitumor agent.

Eight polyhydroxy triterpenoid acids, hederagenin, (4α)-23-hydroxybetulinic acid, maslinic acid, corosolic acid, arjunolic acid, asiatic acid, caulophyllogenin, and madecassic acid, with 2, 3, and 4 hydroxyl substituents, were identified and quantified in the dichloromethane extract of Eucalyptus globulus wood by comparing their GC-retention time and mass spectra with standards. Two other triterpenoid acids were tentatively identified by analyzing their mass spectra, as (2α)-2-hydroxybetulinic acid and (2α,4α)-2,23-dihydroxybetulinic acid, with 2 and 3 hydroxyl substituents. Two MS detectors were used, a quadrupole ion trap (QIT) and a quadrupole mass filter (QMF). The EI fragmentation pattern of the trimethylsilylated polyhydroxy structures of these triterpenoid acids is characterized by the sequential loss of the trimethylsilylated hydroxyl groups, most of them by the retro-Diels-Alder (rDA) opening of the C ring with a π-bond at C12-C13. The rDA C-ring opening produces ions at m/z 320 (or 318) and m/z 278 (or 277, 276, 366). Sequential losses of the hydroxyl groups produce ions with m/z from [M - 90] to [M - 90*y], where y is the number of hydroxyl substituents present (from 2 to 4). Moreover, specific cleavage in ring E was observed, passing from m/z 203 to m/z 133 and conducting other major fragments such as m/z 189.

Polyscias filicifolia (Araliaceae) is broadly used in traditional medicine in Southeast Asia due to its antimicrobial, immunomodulating and cytotoxic activities. The main groups of compounds responsible for pharmacological effects are believed to be oleanolic triterpene saponins. However, Polyscias plants demonstrate relatively slow growth in natural conditions, which led to applying a developing sustainable source of plant material via primary (PSE), secondary (DSE) and direct somatic embryogenesis from DSE (TSE). The AFLP and metAFLP genotyping resulted in 1277 markers, amplified by a total of 24 pairs of selective primers. Only 3.13% of the markers were polymorphic. The analysis of variance showed that the PSE and TSE regenerants differed only in terms of root number, while the DSE plantlets differed for all studied morphological characteristics. Further, the chemical analysis revealed that oleanolic acid (439.72 µg/g DW), ursolic acid (111.85 µg/g DW) and hederagenin (19.07 µg/g DW) were determined in TSE regenerants. Our results indicate that direct somatic embryogenesis ensures the production of homogeneous plant material, which can serve as a potential source of triterpene compounds. Plants obtained via somatic embryogenesis could also be reintroduced into the natural environment to protect and preserve its biodiversity.

WOS:000709117200027 The study aims to determine the secondary metabolites of Hypericum androsaemum L. extracts by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and investigate the antioxidant and cytotoxic activities of the plant. Cytotoxic activity was evaluated by MTT assay, and apoptosis induction abilities on human prostate adenocarcinoma (PC-3), and hepatocellular carcinoma (Hep G2) cell lines. Accordingly, major secondary metabolites were found as hederagenin (762 +/- 70.10 mu g/g) in the leaves dichloromethane (LD), herniarin (167 +/- 1.50 mu g/g) in fruit dichloromethane (FD), (-)-epicatechin (6538 +/- 235.36 mu g/g) in the leaves methanol (LM), (-)-epigallocatechin gallate (758 +/- 20.46 mu g/g) in the fruit methanol (FM), and caffeic acid (370 +/- 8.88 mu g/g) in the fruit water (FW), and (3313 +/- 79.51 mu g/g) in the leaves water (LW) extracts. LM exerted strong antioxidant activity in DPPH free (IC50 10.94 +/- 0.08 mu g/mL), and ABTS cation radicals scavenging (IC50 9.09 +/- 0.05 mu g/mL) activities. FM exhibited cytotoxic activity with IC50 values of 73.23 +/- 3.06 mu g/mL and 31.64 +/- 2.75 mu g/mL on PC-3 and Hep G2 cell lines, respectively. Being the richest extract in terms of quillaic acid (630 +/- 18.9 mu g/g), which is a well-known cytotoxic triterpenoid with proven apoptosis induction ability on different cells, FM extract showed apoptosis induction activity with 64.75% on PC-3 cells at 50 mu g/mL concentration. The study provides promising results about the potential of Hypericum androsaemum on cancer prevention.

Interest in finding plant-based herbicides to supplement synthesized herbicides is increasing. Although the extract of Sapindus mukorossi Gaertn has been reported to have herbicidal activity, little is known about phytotoxic substances and their efficacy of weed control in the field. To identify phytotoxic substances, the bioassay-guided fractionation by column chromatography and high-speed counter-current chromatography (HSCCC) was carried out. The phytotoxic activity assay, performed by the agar medium method, showed that the 70% ethanol fraction exhibited strong root growth inhibition against Trifolium pratense with an 50% inhibitory concentration (IC50) value of 35.13 mg/L. An active compound was isolated from the 70% ethanol fraction and identified as hederagenin 3-o-β-D-xylopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (Compound A). Compound A had an IC50 value of 16.64 mg/L. Finally, a new formulation was prepared based on the 70% ethanol fraction, which exhibited good efficacy against broadleaf weeds in a carrot field. The fresh weight control efficacy was 78.7% by 45 days after treatment at the dose of 1500 g a. i./ha. Hence, the extract of S. mukorossi pulp could be a promising supplement to the synthesized herbicides. Furthermore, compound A from S. mukorossi may be responsible for its phytotoxic activity.

Streptococcus pneumoniae is an important pathogen that causes otitis media, pneumonia, meningitis and bacteremia. As an important virulence factors of S. pneumoniae, pneumolysin (PLY) can penetrate cell membranes and lead to cell lysis and inflammation, which is one of the main causes of infection and damage of S. pneumoniae. Therefore, using pneumolysin as a target to study its inhibitors can provide a new treatment strategy for pneumococcal disease. This study analyzed the inhibitory effect of the natural compound hederagenin on PLY in vitro. The results show that hederagenin has great potential as a new strategy for the treatment of pneumococcal diseases.

Background. Huangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer’s disease (AD). Methods. The active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE. Results. Compound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells. Conclusion. HQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD.

A new hederagenin-type triterpene saponin; hederagenin 28-O-?-D-galactopyranosyl-(1?6)-?-D-glucopyranosyl ester named sumbulianoside A (1), together with twelve known saponins were isolated from the n-butanol extract of Cephalaria sumbuliana (Caprifoliaceae) from which, one known saponin, dipsacus saponin A (2) was isolated, for the first time from Cephalaria species. The structures of the isolated compounds were elucidated by 1 D and 2 D NMR and HRESIMS analyses. Cytotoxic activities were investigated on A549, Hela, PANC1, SHSY5Y cells and non-cancerous cell HEK293 by MTT method and immunomodulatory activities were evaluated against activated H3N2 seasonal virus in whole blood by measuring IL-4, IFN-?, IL-1? cytokine level with ELISA. According to the cytotoxicity results, compounds 1 and 2 did not possess significant cytotoxicity, while only compound 2 induced significant IL-4 production (** p 0.5). © 2021 Informa UK Limited, trading as Taylor & Francis Group., FYL-2019-20471, The authors would like to thank Research Grant Office of Ege University (FYL-2019-20471) for financial support, acknowledge to Prof. Dr. H. Sumbul and Assoc. Prof. Dr. R. S. Gokturk for collection and identification of the plant. Thanks are also due to TUBITAK (Marmara Research Center, Gebze, Kocaeli, Turkey) for NMR and HR-ESI/MS analysis. And finally, we thank Ege University Science and Technology Centre for running NMR (400?MHz) spectra and Ege University, Central Research Test and Analysis Laboratory Application and Research Center for GC-MS analysis.

Two newly described oleanane-type saponins (1-2), named tchihatchewosides A-B, along with thirteen known compounds, were isolated from the aerial parts of Cephalaria tchihatchewii using several type of chromatography processes. The structures of all compounds (1-15) were determined by spectroscopic (1D-and 2D-NMR, HR-ESI/ MS) and chemical methods. The cytotoxic activities on CCD 34Lu, A549, CRL5807, CRL 5826, HTB-177 and HeLa cell lines of newly described compounds 1-2 and 1a-2a were evaluated by MTT method using doxorubicin as positive control. Immunomodulatory activity was performed with PMA plus ionomycin in stimulated whole blood cells treated with saponins. The supernatant was analyzed for IL-4, IFN-gamma and IL18 cytokines by ELISA. DMSO was considered as the negative control. The results showed that the only compound 1a was exhibited moderate cytotoxicity against CRL 5826 and CCD 34Lu cells. The compounds 1-2 and prosapogenins 1a-2a stimulated IL18 cytokine release, indicating that they might potentially stimulate the innate immune response., Ege University Scientific Research Projects Coordination Unit [FDK-2019-20292], This study was supported by Ege University Scientific Research Projects Coordination Unit (Project Number: FDK-2019-20292). The authors are grateful to Prof. Dr. H. Sumbul and Prof. Dr. R. S. Gokturk for the collection and identification of the plant. We thank TUBITAK National Metrology Institute for running 600 MHz NMR spectra and HRESI/MS spectra, Ege University Science and Technology Centre for running 400 MHz NMR spectra. And finally, we thank Ege University, Central Research Test and Analysis Laboratory Application and Research Center for GC-MS analysis.

Multidrug resistance (MDR) has become a major obstacle to malignancies treatment by chemotherapeutic drugs, therefore, it is important to develop MDR reversal agents with high activity. We have previously found that the hederagenin (HD) derivative HBQ showed good tumor MDR reversal activity in vitro and in vivo but had poor solubility. In this study, to enhance the aqueous solubility and tumor MDR reversal activity of HBQ, three series of HD derivatives were designed and synthesized. Nitrogen-containing heterocyclic-substituted, PEGylated, and ring-A substituted derivatives significantly reversed the MDR phenotype of KBV (multidrug-resistant oral epidermoid carcinoma) cells toward paclitaxel at a concentration of 10 μM in MTT assays. The PEGylated derivatives 10c–10e had increased aqueous solubility compared with HBQ by 18–657 fold, while maintaining tumor MDR reversal activity. The most in vitro active compound 10c possessed good chemical stability to an esterase over 24 h and enhanced the sensitivity of KBV cells to paclitaxel and vincristine with IC50 values of 4.58 and 0.79 nM, respectively. Mechanism studies indicated that compound 10c increased the accumulation of P-glycoprotein (P-gp) substrates rhodamine 123 and Flutax1 in KBV cells and MCF-7T (paclitaxel-resistant breast carcinoma) cells, that is to say, compound 10c exerted the reversal effect of tumor MDR by inhibiting the efflux function of P-gp. Finally, the structure–activity relationships were further investigated by analyzing the relationship between structure and tumor MDR reversal activity of HD derivatives. This study highlights the potential of PEGylated HD derivatives such as compound 10c for the development of tumor MDR reversal agents and provides information for the further improvement of the aqueous solubility and tumor MDR reversal activity of HD derivatives in the future.

Two new dammarane-type triterpenoid saponins, 3β-(α-l-arabinopyranosyloxy)-24,25-dihydroxydammar-20-en-12α-yl 6-deoxy-β-d-glucopyranoside (1) and (24R)-3β-[(4-O-acetyl-α-l-arabinopyranosyl)oxy]-25-hydroxy-20,24-epoxydammaran-12β-yl 6-deoxy-β-d-glucopyranoside (2), and fourteen known triterpenoids were isolated from the 70 % MeOH extract of the leaves of Cyclocarya paliurus. Their structures were established based on analyses of spectroscopic data. All compounds were tested for their inhibitory activities against the 11β-HSD1 enzyme. Hederagenin (13) exhibited moderate inhibitory effect for mouse 11β-HSD1 with an IC50 value of 0.16±0.04 μM.

Autophagy inhibition has been demonstrated to increase the efficacy of conventional chemotherapy. In this study, we identified hederagenin, a triterpenoid derived from Hedera helix, as a potent inhibitor of autophagy and then hypothesized that hederagenin might synergize with chemotherapeutic drugs (e.g., cisplatin and paclitaxel) to kill lung cancer cells. Firstly, we observed that hederagenin induced the increased autophagosomes in lung cancer cells concomitantly with the upregulation of LC3-II and p62, which indicated the impairment of autophagic flux. The colocalization assay indicated hederagenin could not block the fusion of lysosomes and autophagosomes, whereas the lysosomal acidification might be inhibited by hederagenin as revealed by the reduced staining of acidity-sensitive reagents (i.e., Lysotracker and acridine orange). The aberrant acidic environment then impaired the function of lysosome, which was evidenced by the decrease of mature cathepsin B and cathepsin D. Lastly, hederagenin, in agree with our hypothesis, promoted pro-apoptotic effect of cisplatin and paclitaxel with the accumulation of reactive oxygen species (ROS); while the synergistic effect could be abolished by the ROS scavenger, N-acetyl-L-cysteine. These data summarily demonstrated hederagenin-induced accumulation of ROS by blocking autophagic flux potentiated the cytotoxicity of cisplatin and paclitaxel in lung cancer cells.

Chocolate vine (Akebia quinata) is consumed as a fruit and is also used in traditional medicine. In order to identify the bioactive components of A. quinata, a phytosterol glucoside stigmasterol-3-O-&beta, d-glucoside (1), three triterpenoids maslinic acid (2), scutellaric acid (3), and hederagenin (4), and three triterpenoidal saponins akebia saponin PA (5), hederacoside C (6), and hederacolchiside F (7) were isolated from a 70% EtOH extract of the fruits of A. quinata (AKQU). The chemical structures of isolates 1&ndash, 7 were determined by analyzing the 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data. Here, we evaluated the effects of AKQU and compounds 1&ndash, 7 on insulin secretion using the INS-1 rat pancreatic &beta, cell line. Glucose-stimulated insulin secretion (GSIS) was evaluated in INS-1 cells using the GSIS assay. The expression levels of the proteins related to pancreatic &beta, cell function were detected by Western blotting. Among the isolates, stigmasterol-3-O-&beta, d-glucoside (1) exhibited strong GSIS activity and triggered the overexpression of pancreas/duodenum homeobox protein-1 (PDX-1), which is implicated in the regulation of pancreatic &beta, cell survival and function. Moreover, isolate 1 markedly induced the expression of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), insulin receptor substrate-2 (IRS-2), phosphoinositide 3-kinase (PI3K), and Akt, which regulate the transcription of PDX-1. The results of our experimental studies indicated that stigmasterol-3-O-&beta, d-glucoside (1) isolated from the fruits of A. quinata can potentially enhance insulin secretion, and might alleviate the reduction in GSIS during the development of T2DM.

Saponin isolated from medicinal plants is a naturally occurring bioorganic molecule with high molecular weight and its aglycone water non soluble part nucleus having to carbon atoms besides one or two sugar moieties water soluble part containing at least or carbon atoms respectively The complexity of saponin chemistry maybe considered as a gap for many scientists and researchers to understand the relationship between the chemical structure and its medical or pharmaceutical behavior Recently the increase in demand of saponin applications was observed due to various biological medicinal and pharmaceutical actions Therefore this present review article provides detailed information about the chemistry of saponin especially triterpenoid saponin Classifications chemical structure the possible traditional isolation ways qualitative and quantitative determination of saponins were included exclusively Examples of mono and bidesmosidic structure of oleanolic acid and hederagenin also outlined Structural differences between triterpenoid steroid and alkaloid glycosides were summarized according to their atoms rings and functional groups

Natural product studies explore potential and interesting new compounds to discover innovative drugs. Nigella sativa (N. sativa) (Ranunculaceae) is traditionally used to treat diabetes. Flavonoids and triterpenoid mostly show anti-diabetic activity. The current study aim to identify new compounds by a systematic study of the anti-oxidant and anti-diabetic activity of aerial parts of N. sativa concerning. Phytochemicals were isolated from the methanolic extract of aerial parts of the plant by column chromatography and identified by nuclear magnetic resonance spectroscopy and mass spectroscopy. A new triterpenoid saponin glycoside was isolated along with flavonoids. The anti-diabetic study was carried out by DPPH, ABTS, &alpha, glucosidase, and protein tyrosine phosphatase 1B assays at doses of 12.5 to 250 &micro, M. The isolated phytochemicals were identified as 3-O-(&beta, d-xylopyranosyl-(1-3)-&alpha, l-rhamnopyrnaosyl-(1-2)-&alpha, l-arabinopyranosyl]-28-O-(&alpha, l-rhamno-pyranosyl-(1-4)-&beta, d-glucopyranosyl-(1-6)-&beta, d-glucopyranosyl] hederagenin (1), flaccidoside III (2), catechol (3), quercetin-3-gentiobiosides (4), magnoflorine (5), nigelflavonoside B (6), nigelloside (7), quercetin sphorotrioside (8), kaempferol-3, 7-diglucoside (9), kaempferol 3-O-rutinoside (10), rutin (11), 3-O-[&alpha, l-rhamnopyranosyl-(1&rarr, 2)-&alpha, l-arabinopyranpsylhederagenin (12), 3&beta, 23,28-trihydroxyolean-12-ene-3-O-&alpha, l-arabinopyranoside(1&rarr, 4)-a-rhamnopyranosyl,(1&rarr, 4)-&beta, d-gluco-pyranoside (13), 3-O-&alpha, l-arabinopyranpsyl]-28-O-&beta, d-gluco-pyranosyl hederagenin (14), and &alpha, hederin (15). These were isolated and are reported for the first time in this study. Compared 13 was identified as a new compound. Compound 2 was isolated for first time from the genus Nigella. Compound 6 was found to be the most active in the DPPH, and ABTS assays and compound 10 was found to be the most active in the &alpha, glucosidase assay, with IC50 32.7 &plusmn, 0.1, 95.18 &plusmn, 0.9, 214.5 &plusmn, 0.0 &micro, &Mu, respectively. Compound 12, at a dose of 125 &micro, showed anti-diabetic activity in a PTP1B assay with IC50 91.30 &plusmn, 2.5 &micro, In conclusion, the anti-diabetic activity of N. sativa is due to its flavonoids and TTSGs. Therefore, our studies suggest that the aerial parts of N. sativa are also a valuable and alternate source of valuable phytochemicals that could be used to develop anti-oxidant and anti-diabetic medicines.

Ilex asprella is a medicinal plant that is used extensively in southern China. The plant contains ursane-type triterpenoids and triterpenoid saponins which are known to be responsible for its pharmacological activities. Previously, a transcriptomic analysis of I. asprella was carried out and the gene IaAS1, which is important in the formation of the core structure α-amyrin, was identified. However, the genes related to the subsequent derivatization of the core structures of the triterpenoid remain largely unknown. Herein, we describe the cloning and functional characterization of an amyrin 28-carboxylase IaAO1 (designated as IaCYP716A210) and a glycosyltransferase IaAU1 (designated as UGT74AG5), based on transcriptomic data. The expression of IaAO1 in an α-amyrin producing yeast strain led to the accumulation of ursolic acid. An enzyme assay using recombinant protein IaAU1 purified from E. coli revealed that IaAU1 can catalyze the conversion of ursolic acid to ursolic acid 28-O-β-D-glucopyranoside. IaAU1 has regiospecificity for catalyzing the 28-O-glucosylation of ursane-/oleanane-type triterpene acids, as it can also catalyze the conversion of oleanolic acid, hederagenin, and ilexgenin A to their corresponding glycosyl compounds. Moreover, co-expression of IaAO1 and IaAU1 in the α-amyrin-producing yeast strain led to the production of ursolic acid 28-O-β-D-glucopyranoside, although in relatively low amounts. Our study reveals that IaAO1 and IaAU1 might play a role in the biosynthesis of pentacyclic triterpenoid saponins in I. asprella and provides insights into the potential application of metabolic engineering to produce ursane-type triterpene glycosides.

Hederagenin (HED) is a bioactive natural compound of pentacyclic triterpenes extracted from many medicinal plants. It has a wide range of antitumor cytotoxic effects and significant anti-inflammation effects. However, at present, it is unclear whether HED can inhibit cardiac remodelling caused by diabetic cardiomyopathy. In this study, we evaluated the effects of HED on pathological abnormalities in cardiac structures and cardiac insufficiency caused by diabetic cardiomyopathy and focused on the inflammatory signalling pathways of the diabetic heart. Treatment with HED reduced pro-inflammatory cytokines, the heart and body mass of diabetic db/db mice but had no effect on fasting plasma glucose (FPG). Moreover, after HED treatment, the cardiac dysfunction of diabetic mice was relieved, and myocardial hypertrophy and fibrosis decreased. Furthermore, HED inhibited the nuclear translocation of nuclear factor-κB (NF-κB) and Smads and decreased the transcriptional activity of NF-κB and Smads. Additionally, the expression levels of transforming growth factor (TGF)-β1 and collagen I, which are target downstream molecules of the NF-κB and Smads signalling pathways, were also decreased in diabetic hearts. Taken together, our findings suggest that the cardioprotective effect of HED may be achieved by reducing the activation of inflammation-associated NF-κB and Smads signalling. We suggest that the protective effect of HED on the diabetic heart, as revealed in this study, should be further explored in-depth to elucidate its cell biology and molecular mechanisms.

Background: Members of the cytochrome P450 (CYP450) and UDP-glycosyltransferase (UGT) gene superfamily have been shown to play essential roles in regulating secondary metabolite biosynthesis. However, the systematic identification of CYP450s and UGTs has not been reported in Aralia elata (Miq.) Seem, a highly valued medicinal plant. Results: In the present study, we conducted the RNA-sequencing (RNA-seq) analysis of the leaves, stems, and roots of A. elata, yielding 66,713 total unigenes. Following annotation and KEGG pathway analysis, we were able to identify 64 unigenes related to triterpenoid skeleton biosynthesis, 254 CYP450s and 122 UGTs, respectively. A total of 150 CYP450s and 92 UGTs encoding >300 amino acid proteins were utilized for phylogenetic and tissue-specific expression analyses. This allowed us to cluster 150 CYP450s into 9 clans and 40 families, and then these CYP450 proteins were further grouped into two primary branches: A-type (53%) and non-A-type (47%). A phylogenetic analysis of 92 UGTs and other plant UGTs led to clustering into 16 groups (A-P). We further assessed the expression patterns of these CYP450 and UGT genes across A. elata tissues, with 23 CYP450 and 16 UGT members being selected for qRT-PCR validation, respectively. From these data, we identified CYP716A295 and CYP716A296 as the candidate genes most likely to be associated with oleanolic acid synthesis, while CYP72A763 and CYP72A776 were identified as being the most likely to play roles in hederagenin biosynthesis. We also selected five unigenes as the best candidates for oleanolic acid 3-O-glucosyltransferase. Finally, we assessed the subcellular localization of three CYP450 proteins within Arabidopsis protoplasts, highlighting the fact that they localize to the endoplasmic reticulum.Conclusions: This study presents a systematic analysis of the CYP450 and UGT gene family in A. elata and provides a foundation for further functional characterization of these two multigene families.

The study was aimed to estimate the effect of plant secondary metabolites present in ruminants diet and phytogenic feed additives on liver microsomal metabolism of albendazole and fenbendazole. The selected phytocompounds comprised of flavonoids (apigenin, quercetin) and saponins (hederagenin, medicagenic acid). The experiments were performed on liver microsomal fraction obtained from routinely slaughtered cows. The intensity of albendazole and fenbendazole metabolism in the presence of flavonoids and saponins was analyzed in equimolar concentration (100 μM). The obtained results revealed that both flavonoids and saponins intensify the metabolism of albendazole and fenbendazole in bovine microsomes. In the case of albendazole, apigenin and quercetin doubled the amount of degraded drug and the amount of produced albendazole sulfoxide. Additionally, both flavonoids increased the amount of produced albendazole sulfone. Saponins, hederagenin, and medicagenic acid intensified the degradation of albendazole (1.8-fold) and the production of albendazole sulfoxide (twofold). Medicagenic acid inhibited the production of albendazole sulfone. In the case of fenbendazole, the degradation of the drug and the production of oxfendazole were increased four and five times in the presence of saponins and flavonoids, respectively. The enhancement of benzimidazoles' metabolism caused by the studied plant metabolites could change pharmacokinetics and the efficacy of benzimidazoles' treatment in cattle.