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1.
Molecules ; 29(9)2024 Apr 26.
Article En | MEDLINE | ID: mdl-38731501

Bacterial infection is a thorny problem, and it is of great significance to developing green and efficient biological antibacterial agents that can replace antibiotics. This study aimed to rapidly prepare a new type of green antibacterial nanoemulsion containing silver nanoparticles in one step by using Blumea balsamifera oil (BBO) as an oil phase and tea saponin (TS) as a natural emulsifier and reducing agent. The optimum preparation conditions of the AgNPs@BBO-TS NE were determined, as well as its physicochemical properties and antibacterial activity in vitro being investigated. The results showed that the average particle size of the AgNPs@BBO-TS NE was 249.47 ± 6.23 nm, the PDI was 0.239 ± 0.003, and the zeta potential was -35.82 ± 4.26 mV. The produced AgNPs@BBO-TS NE showed good stability after centrifugation and 30-day storage. Moreover, the AgNPs@BBO-TS NE had an excellent antimicrobial effect on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. These results demonstrated that the AgNPs@BBO-TS NE produced in this study can be used as an efficient and green antibacterial agent in the biomedical field.


Anti-Bacterial Agents , Emulsions , Green Chemistry Technology , Metal Nanoparticles , Microbial Sensitivity Tests , Particle Size , Silver , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silver/chemistry , Silver/pharmacology , Metal Nanoparticles/chemistry , Staphylococcus aureus/drug effects , Plant Oils/chemistry , Plant Oils/pharmacology , Pseudomonas aeruginosa/drug effects , Escherichia coli/drug effects , Escherichia coli/growth & development , Saponins/chemistry , Saponins/pharmacology
2.
Nat Prod Res ; 38(11): 1956-1960, 2024 Jun.
Article En | MEDLINE | ID: mdl-38739565

Magonia pubescens is a natural species from the Brazilian cerrado biome. Its fruits and seeds are used in the treatment of seborrheic dermatitis, a common inflammatory skin disease. In this work, the known compounds lapachol, stigmasterol, maniladiol and scopoletin were isolated from hexane and dichloromethane extracts of M. pubescens branches. The aqueous extract of this material was fractioned through a liquid-liquid partition and the obtained fractions were analyzed by UHPLC-MS/MS. The results obtained were compared with data from three databases, leading to the putative identification of 51 compounds from different classes, including flavonoids, saponins and triterpenes. The cytotoxicity of aqueous fractions was assayed against breast cancer (MDA-MB-231) and leukemia (THP-1 and K562) cells. The best activity was observed for fraction AE3 against MDA-MB-231 cells (IC50 30.72 µg.mL-1).


Antineoplastic Agents, Phytogenic , Breast Neoplasms , Phytochemicals , Plant Extracts , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Breast Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Female , Phytochemicals/pharmacology , Phytochemicals/chemistry , Triterpenes/pharmacology , Triterpenes/chemistry , Brazil , Leukemia/drug therapy , Flavonoids/pharmacology , Flavonoids/chemistry , K562 Cells , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Saponins/pharmacology , Saponins/chemistry , THP-1 Cells , Molecular Structure
3.
Chin J Nat Med ; 22(5): 466-480, 2024 May.
Article En | MEDLINE | ID: mdl-38796219

Sixteen new dammarane-type triterpenoid saponins (1-16) featuring diverse structural variations in the side chain at C-17, along with twenty-one known analogues (17-37), have been isolated from the rhizomes of Gynostemma longipes C. Y. Wu, a plant renowned for its medicinal and edible properties. The structural elucidation of these compounds was accomplished through comprehensive analyses of 1D and 2D NMR and HRMS spectroscopic data, supplemented by comparison with previously reported data. Subsequent assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells (PC12 cells) revealed that nine saponins exhibited significant anti-hypoxic activities. Further investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that compounds 22 and 36 markedly reduced the levels of hypoxia-induced apoptosis. Additionally, these compounds were found to decrease the release of lactate dehydrogenase (LDH) and malondialdehyde (MDA), while increasing the activity of superoxide dismutase (SOD), thereby indicating that the saponins could mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative stress. These findings offer substantial evidence for the future utilization and development of G. longipes, identifying dammarane-type triterpenoid saponins as its active anti-hypoxic constituents.


Apoptosis , Dammaranes , Gynostemma , Saponins , Triterpenes , PC12 Cells , Triterpenes/pharmacology , Triterpenes/chemistry , Gynostemma/chemistry , Rats , Animals , Apoptosis/drug effects , Molecular Structure , Saponins/pharmacology , Saponins/chemistry , Saponins/isolation & purification , Oxidative Stress/drug effects , Malondialdehyde/metabolism , Superoxide Dismutase/metabolism , Rhizome/chemistry , Cell Hypoxia/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , L-Lactate Dehydrogenase/metabolism , Protective Agents/pharmacology , Protective Agents/chemistry
4.
Nature ; 629(8013): 937-944, 2024 May.
Article En | MEDLINE | ID: mdl-38720067

QS-21 is a potent vaccine adjuvant and remains the only saponin-based adjuvant that has been clinically approved for use in humans1,2. However, owing to the complex structure of QS-21, its availability is limited. Today, the supply depends on laborious extraction from the Chilean soapbark tree or on low-yielding total chemical synthesis3,4. Here we demonstrate the complete biosynthesis of QS-21 and its precursors, as well as structural derivatives, in engineered yeast strains. The successful biosynthesis in yeast requires fine-tuning of the host's native pathway fluxes, as well as the functional and balanced expression of 38 heterologous enzymes. The required biosynthetic pathway spans seven enzyme families-a terpene synthase, P450s, nucleotide sugar synthases, glycosyltransferases, a coenzyme A ligase, acyl transferases and polyketide synthases-from six organisms, and mimics in yeast the subcellular compartmentalization of plants from the endoplasmic reticulum membrane to the cytosol. Finally, by taking advantage of the promiscuity of certain pathway enzymes, we produced structural analogues of QS-21 using this biosynthetic platform. This microbial production scheme will allow for the future establishment of a structure-activity relationship, and will thus enable the rational design of potent vaccine adjuvants.


Biosynthetic Pathways , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saponins/biosynthesis , Saponins/metabolism , Saponins/chemistry , Metabolic Engineering , Adjuvants, Immunologic/biosynthesis , Adjuvants, Immunologic/metabolism
5.
Bioorg Med Chem ; 106: 117737, 2024 May 15.
Article En | MEDLINE | ID: mdl-38718553

Ursolic acid and uvaol are naturally occurring triterpenoids that exhibit a broad spectrum of pharmacological activities, including cytotoxicity. However, a primary challenge in the development of ursane-type pentacyclic triterpenoids for pharmacological use is their poor aqueous solubility, which can impede their effectiveness as therapeutics agents. In this study, we present the facile synthesis of ursolic acid monodesmosides and uvaol bidesmosides, incorporating naturally occurring and water-soluble pentoses and deoxyhexose sugar moieties of opposite d- and l-configurations at the C3 or C3/C28 positions of the ursane core. The twenty synthetic saponins were evaluated in vitro for their cytotoxicity against lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1) cell lines. Notably, all the bidesmosidic uvaol saponins were shown to be cytotoxic as compared to their non-cytotoxic parent triterpenoid. For each series of ursane-type saponins, the most active compounds were 3-O-α-l-arabinopyranosyl ursolic acid (3h) and 3,28-di-O-α-l-rhamnopyranosyl uvaol (4f), showing IC50 values in the low micromolar range against A549 and DLD-1 cancer lines.


Drug Screening Assays, Antitumor , Saponins , Triterpenes , Humans , Saponins/pharmacology , Saponins/chemical synthesis , Saponins/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Triterpenes/chemical synthesis , Cell Line, Tumor , Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Molecular Structure , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Pentacyclic Triterpenes
6.
Food Chem ; 451: 139521, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38703735

This study explored the use of ionic liquid-ultrasound (ILU)-assisted extraction to enhance the extraction rate of Platycodon grandiflorum saponins (PGSs), and the content, extraction mechanism, antioxidant activity, whitening, and antiaging activity of PGSs prepared using ILU, ultrasound-water, thermal reflux-ethanol, and cellulase hydrolysis were compared. The ILU method particularly disrupted the cell wall, improved PGS extraction efficiency, and yielded a high total saponin content of 1.45 ± 0.02 mg/g. Five monomeric saponins were identified, with platycodin D being the most abundant at 1.357 mg/g. PGSs displayed excellent in vitro antioxidant activity and exhibited inhibitory effects on tyrosinase, elastase, and hyaluronidase. The results suggest that PGSs may have broad antioxidant, skin-whitening, and antiaging potential to a large extent. Overall, this study provided valuable insights into the extraction, identification, and bioactivities of PGSs, which could serve as a reference for future development and application of these compounds in the functional foods industry.


Antioxidants , Ionic Liquids , Plant Extracts , Platycodon , Saponins , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Saponins/pharmacology , Saponins/chemistry , Saponins/isolation & purification , Platycodon/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Ionic Liquids/chemistry , Skin Aging/drug effects , Humans , Ultrasonic Waves
7.
Eur J Pharm Biopharm ; 199: 114309, 2024 Jun.
Article En | MEDLINE | ID: mdl-38704102

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.


Alginates , Chitosan , Colitis, Ulcerative , Drug Delivery Systems , Gels , Microspheres , Saponins , Colitis, Ulcerative/drug therapy , Animals , Rats , Alginates/chemistry , Chitosan/chemistry , Drug Delivery Systems/methods , Male , Saponins/pharmacology , Saponins/administration & dosage , Saponins/chemistry , Particle Size , Humans , Colon/drug effects , Colon/metabolism , Colon/pathology , Rats, Sprague-Dawley , Polymers/chemistry , Disease Models, Animal , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Administration, Oral
8.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2385-2392, 2024 May.
Article Zh | MEDLINE | ID: mdl-38812139

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 µg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 µg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.


Breast Neoplasms , Ferroptosis , Reactive Oxygen Species , Rhizome , Saponins , Humans , Saponins/pharmacology , Saponins/chemistry , Ferroptosis/drug effects , MCF-7 Cells , Rhizome/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Reactive Oxygen Species/metabolism , Female , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Cell Proliferation/drug effects , Primulaceae/chemistry
9.
J Ethnopharmacol ; 331: 118331, 2024 Sep 15.
Article En | MEDLINE | ID: mdl-38734392

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng saponins (PNS), as the main active component of Panax notoginseng, shows broad pharmacological effects but with low oral bioavailability. Borneol (BO) is commonly used as an adjuvant drug in the field of traditional Chinese medicine, which has been proven to facilitate the absorption of ginsenosides such as Rg1 and Rb1 in vivo. The presence of chiral carbons has resulted in three optical isomers of BO commercially available in the market, all of which are documented by national standards. AIM OF THE STUDY: This study aimed to investigate the role of BO in promoting the oral absorption of PNS from the perspective of optical configuration and compatibility ratios. MATERIALS AND METHODS: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) method was validated and applied to determine the concentrations of five main saponins in PNS in rat plasma. The kinetic characteristics of PNS were compared when co-administered with BO based on optical isomerism and different compatibility ratios. RESULTS: The results showed that BO promoted the exposure of PNS in rats. Three forms of BO, namely d-borneol (DB), l-borneol (LB), and synthetic borneol (SB), exhibited different promotion strengths. SB elevated PNS exposure in rats more than DB or LB. It is also interesting to note that under different compatibility ratios, SB can exert a strong promoting effect only when PNS and BO were combined in a 1:1 ratio (PNS 75 mg/kg; BO 75 mg/kg). As a pharmacokinetic booster, the dosage of BO is worthy of consideration and should follow the traditional medication principles of Chinese medicine. CONCLUSIONS: This study shed new light on the compatible use of PNS and BO from the perspective of "configuration-dose-influence" of BO. The results provide important basis for the clinical application and selection of BO.


Camphanes , Panax notoginseng , Rats, Sprague-Dawley , Saponins , Tandem Mass Spectrometry , Animals , Panax notoginseng/chemistry , Camphanes/pharmacokinetics , Saponins/pharmacokinetics , Saponins/chemistry , Saponins/administration & dosage , Saponins/blood , Male , Administration, Oral , Rats , Chromatography, High Pressure Liquid , Adjuvants, Pharmaceutic/chemistry , Adjuvants, Pharmaceutic/pharmacokinetics , Biological Availability
10.
Int J Mol Sci ; 25(9)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38731847

Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on human colon cancer HCT116, gastric cancer AGS, squamous carcinoma UM-SCC-6 cells, and human normal fibroblasts with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The amount of apoptotic and dead AGS cells after treatment with yamogenin was estimated with flow cytometry. Also, in yamogenin-treated AGS cells we investigated the reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activity level of caspase-8 and -9, and gene expression at mRNA level with flow cytometry, luminometry, and RT-PCR, respectively. The antioxidant properties of yamogenin were assessed with DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. The antimicrobial potential of the compound was estimated on Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Helicobacter pylori, Campylobacter coli, Campylobacter jejuni, Listeria monocytogenes, Lactobacillus paracasei, and Lactobacillus acidophilus bacteria strains. Yamogenin showed the strongest cytotoxic effect on AGS cells (IC50 18.50 ± 1.24 µg/mL) among the tested cell lines. This effect was significantly stronger in combinations of yamogenin with oxaliplatin or capecitabine than for the single compounds. Furthermore, yamogenin induced ROS production, depolarized mitochondrial membrane, and increased the activity level of caspase-8 and -9 in AGS cells. RT-PCR analysis revealed that this sapogenin strongly up-regulated TNFRSF25 expression at the mRNA level. These results indicate that yamogenin induced cell death via the extrinsic and intrinsic way of apoptosis. Antioxidant study showed that yamogenin had moderate in vitro potential (IC50 704.7 ± 5.9 µg/mL in DPPH and 631.09 ± 3.51 µg/mL in ABTS assay) as well as the inhibition of protein denaturation properties (with IC50 1421.92 ± 6.06 µg/mL). Antimicrobial test revealed a weak effect of yamogenin on bacteria strains, the strongest one being against S. aureus (with MIC value of 350 µg/mL). In conclusion, yamogenin may be a potential candidate for the treatment and prevention of gastric cancers.


Antioxidants , Apoptosis , Reactive Oxygen Species , Saponins , Stomach Neoplasms , Humans , Antioxidants/pharmacology , Saponins/pharmacology , Saponins/chemistry , Stomach Neoplasms/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Cell Line, Tumor , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Anti-Infective Agents/pharmacology , Membrane Potential, Mitochondrial/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry
11.
J Nat Med ; 78(3): 693-701, 2024 Jun.
Article En | MEDLINE | ID: mdl-38587581

Mountain caviar is a fruit of Kochia scoparia that contains momordin Ic as a major saponin constituent. Its extract (MCE) has been shown to suppress blood glucose elevations in the human oral glucose tolerance test (OGTT) as well as increases in blood glucose in OGTT, gastric emptying (GE), and glucose incorporation in the small intestine in rats. However, the effects of MCE and momordin Ic on glucose absorption in mice and these action mechanisms have not been examined for more than 2 decades. Therefore, we herein investigated the effects of MCE, its saponin fraction, and momordin Ic on blood glucose elevations in mice. Mouse blood glucose elevation tests were performed on carbohydrate-loaded mice. The mountain caviar saponin fraction significantly delayed blood glucose elevations in glucose-, sucrose-, and soluble starch-loaded mice. In glucose-loaded mice, the saponin fraction, MCE, and momordin Ic significantly suppressed rapid glucose elevations after glucose loading, but not sucrose loading. A mouse GE study was performed by loading with glucose and phenolphthalein solution. Momordin Ic and MCE strongly suppressed mouse GE. Intestinal glucose absorption was evaluated by the incorporation of 2-deoxyglucose (2-DG) into Caco-2 cell layers and mouse duodenum wall vesicles. The results obtained showed that momordin Ic inhibited the incorporation of 2-DG into Caco-2 cells and mouse duodenum vesicles. Collectively, these results suggest that MCE, particularly the principal saponin, momordin Ic, preferably suppressed glucose-induced blood glucose elevations and delayed carbohydrate-induced glucose elevations in mice. The underlying mechanism was found to involve the suppression of GE and intestinal glucose absorption.


Blood Glucose , Glucose , Hypoglycemic Agents , Plant Extracts , Saponins , Animals , Mice , Saponins/pharmacology , Saponins/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Humans , Caco-2 Cells , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Male , Blood Glucose/drug effects , Glucose/metabolism , Intestinal Absorption/drug effects , Glucose Tolerance Test , Gastric Emptying/drug effects , Fruit/chemistry , Mice, Inbred ICR
12.
Bioorg Chem ; 147: 107351, 2024 Jun.
Article En | MEDLINE | ID: mdl-38593530

Eleven triterpenoid saponins, including five new compounds, which were named densiflorasides A - E (1 - 5), were isolated from aerial parts of Mussaenda densiflora (Rubiaceae). Their structures were elucidated based on spectroscopic and single-crystal X-ray diffraction analyses and chemical methods. All the isolated compounds and the aglycone heinsiagenin A were evaluated for their immunosuppressive and antiosteoclastogenic activities in vitro. Compounds 6 - 8 and heinsiagenin A inhibited osteoclastogenesis, with IC50 values ranging from 8.24 to 17.7 µM. Furthermore, compounds 3, 6 - 8, and heinsiagenin A significantly inhibited T-cell proliferation, with IC50 values ranging from 2.56 to 8.60 µM, and compounds 3 - 5 and 11 inhibited the proliferation of B lymphocytes, with IC50 values ranging from 1.29 to 8.49 µM. Further in vivo experiments indicated that heinsiagenin A could significantly attenuate IMQ-induced psoriasis and DSS-induced colitis in mice.


Cell Proliferation , Dose-Response Relationship, Drug , Immunosuppressive Agents , Saponins , Triterpenes , Saponins/pharmacology , Saponins/chemistry , Saponins/isolation & purification , Animals , Mice , Cell Proliferation/drug effects , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/pharmacology , Triterpenes/isolation & purification , Molecular Structure , T-Lymphocytes/drug effects , Colitis/drug therapy , Colitis/chemically induced , Male , Osteoclasts/drug effects
13.
J Chromatogr A ; 1723: 464716, 2024 May 24.
Article En | MEDLINE | ID: mdl-38640881

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed. The pharmacokinetic parameters of SR were determined using noncompartmental analyses CCK-8 assays were used to detect the cytotoxicity of ASIV, PAE, cimifugin (CIM), prim-o-glucosylcimifugin (POG) and their combinations. Moreover, drug transport was studied using MDCK-MDR1 cells. Western blotting was performed to measure the protein expression levels of P-GP and MRP1. Claudin-5, ZO-1, and F-actin expression was determined via immunohistochemical staining of MDCK-MDR1 cells. harmacokinetic studies revealed that, compared with those of Huangqi Chifeng Tang-Saposhnikoviae Radix (HQCFT-SR), the Tmax of ASIV increased by 11.11 %, and the MRT0-t and Tmax of PAE increased by 11.19 % and 20 %, respectively, in the HQCFT group. Transport studies revealed that when ASIV was coincubated with 28 µM CIM or POG, the apparent permeability coefficient (Papp) increased by 71.52 % and 50.33 %, respectively. Coincubation of PAE with 120 µM CIM or POG increased the Papp by 87.62 % and 60.95 %, respectively. Moreover, CIM and POG significantly downregulated P-gp and MRP1 (P < 0.05), inhibited the expression of Claudin-5, ZO-1, and F-actin (P < 0.05), and affected intercellular tight junctions (TJs). In conclusion, our study successfully established a selective, sensitive and reproducible UPLC‒MS/MS analytical method to detect drug‒drug interactions between SR, AR and PR in vivo and in vitro, which is beneficial for enhancing the therapeutic efficacies of AR and PR. Moreover, this study provides a theoretical basis for further research on the use of SR as a drug carrier.


Drugs, Chinese Herbal , Glucosides , Monoterpenes , Rats, Sprague-Dawley , Saponins , Tandem Mass Spectrometry , Triterpenes , Animals , Glucosides/pharmacokinetics , Glucosides/analysis , Glucosides/chemistry , Glucosides/pharmacology , Saponins/pharmacokinetics , Saponins/pharmacology , Saponins/chemistry , Saponins/analysis , Monoterpenes/analysis , Triterpenes/pharmacology , Triterpenes/pharmacokinetics , Triterpenes/chemistry , Triterpenes/analysis , Dogs , Rats , Madin Darby Canine Kidney Cells , Tandem Mass Spectrometry/methods , Male , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Apiaceae/chemistry , Herb-Drug Interactions , Drug Interactions , Reproducibility of Results
14.
J Nanobiotechnology ; 22(1): 206, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658950

The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.


Carcinoma, Hepatocellular , Liver Neoplasms , Metal-Organic Frameworks , Programmed Cell Death 1 Receptor , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Liver Neoplasms/drug therapy , Carcinoma, Hepatocellular/drug therapy , Animals , Mice , Humans , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Cell Line, Tumor , Immune Checkpoint Inhibitors/pharmacology , Tumor Microenvironment/drug effects , Mice, Inbred BALB C , Saponins/pharmacology , Saponins/chemistry , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunology
15.
J Agric Food Chem ; 72(18): 10339-10354, 2024 May 08.
Article En | MEDLINE | ID: mdl-38682702

The current study aimed to assess the effectiveness of pharmacological intervention with Platycodin D (PD), a critically active compound isolated from the roots of Platycodon grandiflorum, in mitigating cardiotoxicity in a murine model of type 2 diabetes-induced cardiac injury and in H9c2 cells in vitro. Following oral administration for 4 weeks, PD (2.5 mg/kg) significantly suppressed the elevation of fasting blood glucose (FBG) levels, improved dyslipidemia, and effectively inhibited the rise of the cardiac injury markers creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT). PD treatment could ameliorate energy metabolism disorders induced by impaired glucose uptake by activating AMPK protein expression in the DCM mouse model, thereby promoting the GLUT4 transporter and further activating autophagy-related proteins. Furthermore, in vitro experiments demonstrated that PD exerted a concentration-dependent increase in cell viability while also inhibiting palmitic acid and glucose (HG-PA)-stimulated H9c2 cytotoxicity and activating AMPK protein expression. Notably, the AMPK activator AICAR (1 mM) was observed to upregulate the expression of AMPK in H9c2 cells after high-glucose and -fat exposure. Meanwhile, we used AMPK inhibitor Compound C (20 µM) to investigate the effect of PD activation of AMPK on cells. In addition, the molecular docking approach was employed to dock PD with AMPK, revealing a binding energy of -8.2 kcal/mol and indicating a tight interaction between the components and the target. PD could reduce the expression of autophagy-related protein p62, reduce the accumulation of autophagy products, promote the flow of autophagy, and improve myocardial cell injury. In conclusion, it has been demonstrated that PD effectively inhibits cardiac injury-induced type 2 diabetes in mice and enhances energy metabolism in HG-PA-stimulated H9c2 cells by activating the AMPK signaling pathway. These findings collectively unveil the potential cardioprotective effects of PD via modulation of the AMPK signaling pathway.


AMP-Activated Protein Kinases , Diabetes Mellitus, Type 2 , Mice, Inbred C57BL , Platycodon , Saponins , Signal Transduction , Triterpenes , Animals , Saponins/pharmacology , Saponins/chemistry , Saponins/administration & dosage , Mice , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/administration & dosage , Male , Signal Transduction/drug effects , Platycodon/chemistry , Humans , Cell Line , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Rats , Glucose/metabolism
16.
Phytochemistry ; 223: 114099, 2024 Jul.
Article En | MEDLINE | ID: mdl-38641143

Panax notoginseng (Burk.) F.H. Chen is a traditional medicinal herb known as Sanqi or Tianqi in Asia and is commonly used worldwide. It is one of the main raw ingredients of Yunnan Baiyao, Fu fang dan shen di wan, and San qi shang yao pian. It is also a source of cardiotonic pill used to treat cardiovascular diseases in China, Korea, and Russia. Approximately 270 Panax notoginseng saponins have been isolated and identified as the major active components. Although the absorption and bioavailability of saponins are predominantly dependent on the gastrointestinal biotransformation capacity of an individual, minor saponins are better absorbed into the bloodstream and act as active substances than major saponins. Notably, minor saponins are absent or are present in minimal quantities under natural conditions. In this review, we focus on the strategies for the enrichment and production of minor saponins in P. notoginseng using physical, chemical, enzyme catalytic, and microbial methods. Moreover, pharmacological studies on minor saponins derived from P. notoginseng over the last decade are discussed. This review serves as a meaningful resource and guide, offering scholarly references for delving deeper into the exploration of the minor saponins in P. notoginseng.


Drugs, Chinese Herbal , Panax notoginseng , Saponins , Saponins/chemistry , Panax notoginseng/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Molecular Structure
17.
Phytochemistry ; 223: 114104, 2024 Jul.
Article En | MEDLINE | ID: mdl-38657884

Phytochemical investigation on aerial parts of Lysimachia atropurpurea L. (Myrsinaceae), guided by NMR methods, resulted in the isolation and characterization of three previously undescribed triterpenoid saponins named stralysaponins A-C along with five known compounds. Their structures were elucidated by 1D and 2D NMR spectroscopy and HR-ESI-MS. Stralysaponins A-C were categorized into 13ß-28-epoxyoleanane-type triterpenoid saponins, reaffirming their prevalent presence of this type in the Myrsinaceae family and the genus Lysimachia. The identified derivatives share a common four-unit branched sugar chain, with rhamnose as the terminal sugar linked at C-3 of the aglycone. The presence of triterpenoid saponins in L. atropurpurea is reported herein for the first time. This study enriched the chemical diversity of triterpenoid saponins of the genus Lysimachia. Additionally, it demonstrates the effectiveness of NMR-profiling in isolating previously undescribed triterpenoid saponins from Lysimachia spp.


Primulaceae , Saponins , Triterpenes , Saponins/chemistry , Saponins/isolation & purification , Triterpenes/chemistry , Triterpenes/isolation & purification , Primulaceae/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Lysimachia
18.
Food Chem ; 450: 139333, 2024 Aug 30.
Article En | MEDLINE | ID: mdl-38636384

Camellia saponins are important by-products of Camellia Oleifer Abel. processing. In this study, an eco-friendly method based on natural deep eutectic solvents (NaDESs, proline and glycerol at a molar ratio of 2:5) was established to extract saponins from C.oleifera cakes. The content of saponin (702.22 ± 1.28 mg/g) obtained using NaDES was higher than those extracted using water or methanol. UPLC-Q-TOF MS analysis of chemical structure showed that the difference in the extraction technique alter individual saponins. A widely targeted metabolomic approach and KEGG metabolic pathway analysis showed that the upregulated metabolites in the NaDES-based extract mainly included flavonoids, alkaloids, and phenolic acids; and they were involved in arginine and proline metabolism, metabolic pathways, phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, and flavonoid biosynthesis. The present study proposes a selective substitute for use in the extraction of camellia saponins with composition analysis.


Camellia , Metabolomics , Plant Extracts , Saponins , Camellia/chemistry , Camellia/metabolism , Saponins/chemistry , Saponins/metabolism , Saponins/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/metabolism , Solvents/chemistry , Chromatography, High Pressure Liquid , Mass Spectrometry
19.
Food Chem ; 450: 139319, 2024 Aug 30.
Article En | MEDLINE | ID: mdl-38640538

Saponins are considered the main source of the bitter taste of quinoa, however, it has not been confirmed by Song et al. (2024). These authors suggested that saponin extracts contribute to the umami taste, however, the stronger source of the bitter taste may be the flavonoids contained in the extracts. It is an interesting finding in view of the flavonoids role in the field of food sciences. The UPLC-MS results showed that besides saponins, also polyphenols were present in the analyzed samples. However, the presented results of UPLC-MS analysis should be substantially improved, mainly with respect to the reported accurate masses and retention times, as described in details in this comment.


Chenopodium quinoa , Saponins , Taste , Chenopodium quinoa/chemistry , Saponins/chemistry , Chromatography, High Pressure Liquid , Plant Extracts/chemistry , Humans , Mass Spectrometry , Flavoring Agents/chemistry , Flavonoids/chemistry , Flavonoids/analysis
20.
Molecules ; 29(8)2024 Apr 09.
Article En | MEDLINE | ID: mdl-38675511

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.


Antioxidants , Astragalus propinquus , Drugs, Chinese Herbal , Antioxidants/pharmacology , Antioxidants/chemistry , Astragalus propinquus/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Astragalus Plant/chemistry , Oxidative Stress/drug effects , Animals , Flavonoids/chemistry , Flavonoids/pharmacology , Medicine, Chinese Traditional , Saponins/pharmacology , Saponins/chemistry
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