RESUMEN
We evaluated the performance of Zybio EXS2600 matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Zybio Inc., Chongqing, China) for the identification of bacteria from positive blood culture (BC) bottles using Blood Culture Positive Sample Pretreatment Kit (Zybio Inc., Chongqing, China) in comparison to an in-house saponin method. Following a positive signal by the BACTEC™ FX system, confirmation of identification was achieved using subcultured growing biomass used for MALDI-TOF MS analysis. A total of 94 positive BC bottles with 97 bacterial isolates were analyzed. The overall identification rates at the genus and species levels for the saponin method were 89.7% (87/97) and 74.2% (72/97), respectively. With the Zybio Kit, 88.7% (86/97) and 80.4% (78/97) of microorganisms were correctly identified to the genus and species levels, respectively. The saponin method identified 65.3% (32/49) of Gram-positive bacteria at the species level, whereas the Zybio Kit achieved a higher species-level identification rate of 79.6% (39/49) (p = 0.1153). The saponin method with additional on-plate formic acid extraction showed a significantly higher overall identification rate in comparison to the saponin method without that step for both genus (87.6% [85/97] vs. 70.1% [68/97], p = 0.0029) and species level (70.1% [68/97] vs. 46.4% [45/97], p = 0.0008). Identification rates of Gram-negative bacteria showed a higher identification rate, however, not statistically significant with additional Zybio Kit protocol step on both genus (85.4% [41/48] vs. 81.3% [39/48], p = 0.5858) and species level (77.1% [37/48] vs. 75% [36/48], p = 0.8120). Zybio Kit could offer an advantage in species-level identification, particularly for Gram-positive bacteria. The inclusion of on-plate formic acid extraction in the saponin method notably enhanced identification at both genus and species levels for Gram-positive bacteria. The extended protocol provided by the Zybio Kit could potentially offer an advantage in the identification of Gram-negative bacteria at both genus and species levels. Enhancements to the Zybio EXS2600 MALDI-TOF instrument software database are necessary.
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Bacterias , Cultivo de Sangre , Saponinas , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Saponinas/química , Saponinas/análisis , Humanos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/química , Cultivo de Sangre/métodos , Bacterias Gramnegativas/aislamiento & purificación , Juego de Reactivos para Diagnóstico , Bacterias Grampositivas/aislamiento & purificación , Bacterias Grampositivas/clasificación , Técnicas de Tipificación Bacteriana/métodosRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases encountered in clinical practice, which is characterized by the excessive accumulation of triglycerides (steatosis), and a variety of metabolic abnormalities including lipid metabolism and bile acid metabolism are closely related to NAFLD. In China, Gynostemma pentaphyllum is used as functional food and Chinese medicine to treat various diseases, especially NAFLD, for a long time. However, the active components that exert the main therapeutic effects and their mechanisms remain unclear. In this study, Gypensapogenin A was isolated from the total saponins of G. pentaphyllum and prepared as a liposomal delivery system. Gypensapogenin A liposomes could activate FXR, inhibit the expression of CYP7A1 and CYP8B1, increase the expression of CYP27A1, modulate the ratio of CA and CDCA, decrease the content of CA, and increase the content of CDCA, thus forming a virtuous cycle of activating FXR to play a role in lowering blood lipid levels.
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Gynostemma , Metabolismo de los Lípidos , Liposomas , Receptores Citoplasmáticos y Nucleares , Receptores Citoplasmáticos y Nucleares/metabolismo , Liposomas/química , Metabolismo de los Lípidos/efectos de los fármacos , Humanos , Animales , Gynostemma/química , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Saponinas/farmacología , Saponinas/química , Células Hep G2 , Ratones , Ácidos y Sales Biliares/metabolismo , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacosRESUMEN
Platycodon grandiflorum roots (PGR), a widely recognized edible herbal medicine, are extensively used in traditional Chinese medicine for respiratory ailments. PGR are rich in bioactive compounds, particularly triterpenoid saponins, which possess significant pharmaceutical properties, including anti-inflammatory, antifungal, and antioxidant activities. Despite their recognized bioactivity, the purification and enrichment processes of triterpenoid saponins remain underexplored. This study aimed to optimize the extraction and purification of triterpenoid saponins from PGR to enhance resource utilization and minimize waste. Our method involved n-butanol extraction and macroporous adsorption resin, yielding four extracts with varying saponins contents. Qualitative analysis using LC-MS identified 8 triterpenoid saponins across the extracts. Further fragmentation analysis delineated characteristic ion patterns and cleavage pathways for these compounds. Quantitative analysis demonstrated that the separation and purification process effectively increased the triterpenoid saponins content, with the highest levels obtained through 30 % ethanol elution. Notably, the absence of Platycodin D in the 30 % ethanol eluate highlighted potential variations due to the origin, processing, and purification methods. These findings provide theoretical support for the development and utilization of triterpenoid saponins in PGR.
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Raíces de Plantas , Platycodon , Saponinas , Triterpenos , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/análisis , Platycodon/química , Raíces de Plantas/química , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/análisis , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Cromatografía Liquida/métodosRESUMEN
Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and human immunodeficiency virus (HIV). Herein, we developed a highly modular saponin-based nanoparticle platform incorporating Toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, and TLR7/8a adjuvants and their mixtures. These various TLRa-saponin nanoparticle adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific T helper responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform that could improve the design of vaccines and affect modern vaccine development.
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Adyuvantes Inmunológicos , Vacunas contra la COVID-19 , Nanopartículas , SARS-CoV-2 , Saponinas , Agonistas de los Receptores Toll-Like , Animales , Humanos , Ratones , Adyuvantes Inmunológicos/farmacología , Adyuvantes de Vacunas/química , Vacunas contra el SIDA/inmunología , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Citocinas/metabolismo , Nanopartículas/química , Saponinas/farmacología , Saponinas/química , Saponinas/inmunología , SARS-CoV-2/inmunologíaRESUMEN
We present a practical and convergent synthesis of glycoalkaloids solasonine 1 and its saponin derivative 2, incorporating a {3-O-α-L-rhamnopyranosyl-(1â2)-O-[ß-D-glucopyranosyl-(1â3)]-ß-D-galactopyranoside} moiety. The key features of this strategy include the following: (1) AuCl3-tBuCN cooperative catalysis enabling 1,2-trans stereoselective glycosidation of 2-branched trisaccharide trichloroacetimidate donors with steroidal aglycons, in the absence of neighboring group participation; (2) "cyanide effect" mediated regioselective benzoylation of the 4- and 6-hydroxyl groups of galactopyranosyl disaccharide; and (3) an effective approach to prevent orthoester byproduct formation.
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Saponinas , Saponinas/síntesis química , Saponinas/química , Estereoisomerismo , Alcaloides Solanáceos/síntesis química , Alcaloides Solanáceos/química , Alcaloides/síntesis química , Alcaloides/química , CatálisisRESUMEN
As one of a traditional Chinese medicine with dual applications in both medicinal treatment and dietary consumption, the mature seeds of D. lablab were reported to be rich in saponins and have a good effect on inflammatory related diseases. However, the substance basis for its anti-inflammatory activity remains unclear. Thus, a comprehensive phytochemical investigation on triterpenoid saponins from D. lablab seeds was carried out, resulting in the isolation and identification of twenty-one new triterpenoid saponins including dolilabsaponins A1-A4, B, C, D1-D3, E-M, N1, N2 and O (1-21) along with thirteen known analogs (22-34). Notably, the known saponins, 31, 32, and 34 were obtained from Leguminosae family for the first time. The 1H and 13C NMR data of saponins 24 and 28 were firstly reported here. Additionally, lipopolysaccharide (LPS)-stimulated RAW264.7 cells model was utilized to assess inhibitory activities of compounds 1-34 on nitric oxide (NO) production. The results revealed that compounds 1-3, 9, 10, 13-15, 18, 22, 23 and 28-34 significantly suppressed the elevation of NO levels in LPS-induced RAW264.7 cells at the concentration of 30 µM, exhibiting a concentration-dependent manner at 3, 10, and 30 µM. The results suggested that compounds 1-3, 9, 10, 13-15, 18, 22, 23, and 28-34 possessed potential anti-inflammatory activity. Further western blot assay demonstrated that 1, 9, 10, 13, 14, and 18 suppressed inflammatory response via down-regulated the expression levels of inflammatory factors, tumor necrosis factor-alpha and interleukin-6.
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Dolichos , Lipopolisacáridos , Óxido Nítrico , Saponinas , Semillas , Saponinas/farmacología , Saponinas/química , Saponinas/aislamiento & purificación , Ratones , Células RAW 264.7 , Animales , Semillas/química , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Estructura Molecular , Dolichos/química , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificaciónRESUMEN
Gastric cancer (GC)-diabetes co-morbidity is nowadays growing into a rising concern. However, no separate treatment procedures have been outlined for such patients. Phytochemicals and their derivatives can therefore be used as therapeutics as they have greater effectiveness, reduced toxicity, and a reduced likelihood of developing multi-drug resistance in cancer treatments. The present study intended to assess the therapeutic efficacy of Shatavarin-IV - a major steroidal saponin from the roots of Asparagus racemosus, in human gastric adenocarcinoma cell line under hyperglycemic conditions and explore its mechanism of action in controlling GC progression. For the present study, AGS cells were incubated in high glucose-containing media and the effects of Shatavarin-IV therein have been evaluated. Cell proliferation, confocal microscopic imaging, flow-cytometric analysis for cell cycle and apoptosis, immunoblotting, zymography, reverse zymography, wound-healing, colony formation, and invasion assays were performed. Shatavarin-IV has a prominent effect on AGS cell proliferation; with IC50 of 2.463 µ M under hyperglycemic conditions. Shatavarin-IV induces cell cycle arrest at the G0/G1 phase, thereby preventing hyperglycemia-induced excessive cell proliferation that later on leads to apoptotic cell death at 36 h of incubation. Shatavarin-IV further inhibits the migratory and invasive potential of AGS cells by altering the expression patterns of different EMT markers. It also inhibits MMP-9 while promoting TIMP-1 activity and expression; thereby regulating ECM turnover. This is the first report demonstrating the therapeutic efficacy of Shatavarin-IV against AGS cells grown in hyperglycemic conditions, implicating new insights into the treatment paradigm of patients with GC-diabetes co-morbidity.
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Asparagus , Proliferación Celular , Transición Epitelial-Mesenquimal , Hiperglucemia , Saponinas , Humanos , Saponinas/farmacología , Saponinas/química , Saponinas/aislamiento & purificación , Asparagus/química , Transición Epitelial-Mesenquimal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Hiperglucemia/tratamiento farmacológico , Línea Celular Tumoral , Ciclo Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias Gástricas/patología , Neoplasias Gástricas/tratamiento farmacológico , Movimiento Celular/efectos de los fármacosRESUMEN
Gynostemma pentaphyllum has been used as an herbal tea, vegetable, and dietary supplement for hundreds of years in East Asia. The sweet variety, grown in large areas in Fujian Province, China, is an essential source of "Jiaogulan" herbal tea. However, its sweet components are unknown. To investigate the sweet constituents of Fujian "Jiaogulan" and discover new natural high-potency sweeteners, phytochemical and sensory evaluations were combined to obtain 15 saponins, of which 11 (1-11) were sweet-tasting, including 2 new ones with sweetness intensities 20-200 times higher than that of sucrose, and four (12-15) were bitter-tasting. Their structures were elucidated using spectroscopic methods (NMR, MS, IR, UV), hydrolysis, and comparison with literature data. The contents of the 15 saponins were quantitatively analyzed using UPLC-MS/MS in multiple reaction monitoring mode. The contents of 1 and 2 sweet-tasting gypenosides were 9.913 ± 1.735 and 35.852 ± 1.739 mg/kg, respectively. The content of the sweetest compound (6) was 124.969 ± 0.961 mg/kg. Additionally, compound 4 was the most abundant sweet component (422.530 ± 3.702 mg/kg). Furthermore, molecular docking results suggested interactions of sweet saponins with sweet taste receptors. In general, this study revealed the material basis of the Fujian "Jiaogulan" taste.
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Gynostemma , Extractos Vegetales , Receptores Acoplados a Proteínas G , Edulcorantes , Gusto , Gynostemma/química , Humanos , Edulcorantes/química , Extractos Vegetales/química , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Estructura Molecular , Espectrometría de Masas en Tándem , Simulación del Acoplamiento Molecular , Saponinas/química , ChinaRESUMEN
The plant genus Tacca comprises twenty species including Tacca plantaginea, essentially distributed in the Indo-China region. Medicinal preparations from the rhizomes are used traditionally to treat gastrointestinal ailments, stomach aches and inflammatory disorders. A variety of bioactive molecules have been isolated from T. plantaginea, including potent anticancer steroids such as the taccanolides which interfere with microtubules dynamic. Other efficient anticancer natural products have been isolated from the plant, in particular a series of diosgenin/yamogenin-type sapogenins including taccaoside (monodesmosidic) and taccaoside A (bidesmosidic). Taccaoside A displays marked anticancer properties through two complementary mechanisms: a direct action on cancer stem cells via HRas and Pi3K/Akt signaling and an indirect immunomodulatory action via activation of cytotoxic T cells. A similar mechanism of action has been invoked with a total saponin extract from Schizocapsa plantaginea Hance (synonym to T. plantaginea) and the saponin SSPH 1. This saponin reduced tumor growth in mice through stimulation of cytotoxic T lymphocytes. Other bioactive products have been isolated from T. plantaginea, including withanolide-type steroids (plantagiolides, chantriolides), diarylheptanoids (plantagineosides) and different saponins (diosbulbisides, lieguonins). The discussion centers around the mechanism of action of spirostanol saponins, with the objective to promote their study as immuno-active anticancer agents.
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Antineoplásicos Fitogénicos , Saponinas , Espirostanos , Saponinas/farmacología , Saponinas/aislamiento & purificación , Saponinas/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Humanos , Espirostanos/farmacología , Espirostanos/química , Espirostanos/aislamiento & purificación , Animales , Dioscoreaceae/química , Productos Biológicos/farmacología , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Estructura MolecularRESUMEN
Bentonite is a non-metallic mineral with montmorillonite as the main component. It is an environmentally friendly mineral material with large reserves, wide distribution, and low price. Bentonite can be easily modified organically using the surfactant saponin to obtain saponin-modified bentonite (Sap-BT). This study investigates the immobilization of crude enzymes obtained from Trametes versicolor by physical adsorption with Sap-BT. Thus, saponin-modified bentonite immobilized crude enzymes (CE-Sap-BT) were developed to remove benzo[a]pyrene. Immobilization improves the stability of free enzymes. CE-Sap-BT can maintain more than 80% of activity at 45 °C and after storage for 15 d. Additionally, CE-Sap-BT exhibited a high removal rate of benzo[a]pyrene in soil, with 65.69% after 7 d in highly contaminated allotment soil and 52.90% after 6 d in actual soil contaminated with a low concentration of benzo[a]pyrene at a very low laccase dosage (0.1 U/3 g soil). The high catalytic and removal performance of CE-Sap-BT in contaminated sites showed more excellent practical application value.
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Bentonita , Benzo(a)pireno , Enzimas Inmovilizadas , Saponinas , Contaminantes del Suelo , Bentonita/química , Benzo(a)pireno/química , Contaminantes del Suelo/química , Adsorción , Saponinas/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismoRESUMEN
The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of ß-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/ß-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion.
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Alopecia , Emulsiones , Folículo Piloso , Panax notoginseng , Saponinas , Tensoactivos , Alopecia/tratamiento farmacológico , Alopecia/inducido químicamente , Animales , Ratones , Saponinas/administración & dosificación , Saponinas/farmacología , Saponinas/química , Folículo Piloso/efectos de los fármacos , Panax notoginseng/química , Tensoactivos/química , Tensoactivos/administración & dosificación , Femenino , Piel/efectos de los fármacos , Piel/metabolismo , Movimiento Celular/efectos de los fármacos , Masculino , Absorción Cutánea/efectos de los fármacos , Agua/química , Administración CutáneaRESUMEN
Saikosaponins (SS), which are major bioactive compounds in Radix Bupleuri, have long been used clinically for multicomponent, multitarget, and multipathway therapeutic strategies. Programmed cell death (PCD) induction is among the multiple mechanisms of SS and mediates the anticancer efficacy of this drug family. Although SS show promise for anticancer therapy, the available data to explain how SS mediate their key anticancer effects through PCD (apoptosis, autophagy, ferroptosis, and pyroptosis) remain limited and piecemeal. This review offers an extensive analysis of the key pathways and mechanisms involved in PCD and explores the importance of SS in cancer. We believe that high-quality clinical trials and a deeper understanding of the pharmacological targets involved in the signalling cascades that govern tumour initiation and progression are needed to facilitate the development of innovative SS-based treatments. Elucidating the specific anticancer pathways activated by SS and further clarifying how comprehensive therapies lead to cross-link among the different types of cell death will inspire the clinical translation of SS as cancer treatments.
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Apoptosis , Neoplasias , Ácido Oleanólico , Saponinas , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Ácido Oleanólico/química , Humanos , Saponinas/farmacología , Saponinas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Apoptosis/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Transducción de Señal/efectos de los fármacosRESUMEN
Plants from the Amaranthaceae family are a source of oleanolic acid (OA)-type saponins with cytotoxic activity. Two known OA-type saponins, calenduloside E and chikusetsusaponin IVa, were isolated from the roots of Chenopodium strictum Roth. Their structures were confirmed using MS and NMR techniques. This constitutes the inaugural report of the saponins in Ch. strictum. Both the isolated saponins and structurally similar compounds, momordin Ic and OA, were compared for their cytotoxicity against various cancer and normal cell lines (including skin, breast, thyroid, gastrointestinal, and prostate panels). Their effects were dose- and time-dependent, varying with the specific cell line and compound structure. A chemometric approach demonstrated the effects of the compounds on the cell lines. The study discusses the structure-activity observations. The key structural elements for potent cytotoxic activity included the free carboxyl group 28COOH in the sapogenin structure (OA) and the presence of a sugar moiety. The monodesmosides with glucuronic acid (GlcA) at the C3 position of OA were generally more cytotoxic than bidesmosides or OA alone. The addition of xylose in the sugar chain modified the activity towards the cancer cells depending on the specific cell line. OA-type saponins with GlcA (particularly calenduloside E and momordin Ic) represent a promising avenue for further investigation as potential anticancer agents.
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Antineoplásicos Fitogénicos , Ácido Oleanólico , Saponinas , Humanos , Saponinas/farmacología , Saponinas/química , Saponinas/aislamiento & purificación , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Línea Celular Tumoral , Relación Estructura-Actividad , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Amaranthaceae/química , Estructura Molecular , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ensayos de Selección de Medicamentos Antitumorales , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
OBJECTIVE: Solanum nigrum L. (SNL) is a natural drugwith diverse bioactive components and multi-targeted anti-tumor effects, gaining increasing attention in clinical application. METHOD AND RESULTS: This paper reviews the studies on SNL by searching academic databases (Google Scholar, PubMed, Science Direct,and Web of Science, among others), analyzing its chemical compositions (alkaloids, saponins, polysaccharides, and polyphenols, among others), andbriefly describes the anti-tumor mechanisms of the main components. DISCUSSION: This paper discusses the shortcomings of the current research on SNL and proposes corresponding solutions, providing theoretical support for further research on its biological functions and clinical efficacy.
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Antineoplásicos Fitogénicos , Solanum nigrum , Solanum nigrum/química , Humanos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Neoplasias/tratamiento farmacológico , Polisacáridos/farmacología , Polisacáridos/química , Saponinas/farmacología , Saponinas/química , Fitoquímicos/farmacología , Fitoquímicos/química , Polifenoles/farmacología , Polifenoles/química , Animales , Alcaloides/farmacología , Alcaloides/químicaRESUMEN
Some species of the Gentianaceae family are a valuable source of secondary metabolites. However, the phytochemical knowledge of some of these species remains insufficient. Therefore, this work focused on the isolation of the two main secondary metabolites in the methanolic extract from a Gentiana capitata cell suspension using preparative HPLC and the determination of their structure using UHPLC-DAD-IT-MS/MS and NMR methods. Their content in the methanolic extract was quantified using a previously validated HPLC method. The toxicity of the extract and two isolated compounds was also tested on the PC-12 cell line. The structures of the main secondary metabolites were identified as isosaponarin and 3,7,8-Trimethoxy-9-oxo-9H-xanthen-1-yl 6-O-ß-D-ribopyranosyl-ß-D-allopyranoside by comparing the UHPLC-DAD-IT-MS/MS and NMR results with the literature data. The content of isosaponarin was determined to be 0.76 ± 0.04%, and the content of 3,7,8-trimethoxy-9-oxo-9H-xanthen-1-yl 6-O-ß-D-ribopyranosyl-ß-D-allopyranoside was found to be 0.31 ± 0.02% in the dry extract. Additionally, a two-fold increase in the viability of the PC-12 cell line was observed compared to the control after treatment with the methanolic extract at a concentration of 500 µg/mL. These results suggest the potential use of G. capitata cell suspension methanolic extract as a new source of isosaponarin and 3,7,8-trimethoxy-9-oxo-9H-xanthen-1-yl 6-O-ß-D-ribopyranosyl-ß-D-allopyranoside, highlighting their lack of toxicity to the PC-12 (rat pheochromocytoma) cell line.
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Supervivencia Celular , Gentiana , Extractos Vegetales , Animales , Ratas , Células PC12 , Supervivencia Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Gentiana/química , Saponinas/farmacología , Saponinas/química , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem , Espectroscopía de Resonancia MagnéticaRESUMEN
This paper investigated the effect of total saponins from Rhizoma Panacis Majoris on the proliferation, apoptosis, and autophagy of human cervical carcinoma HeLa cells. The saponin content was detected by ultraviolet-visible spectrophotometry. Cell coun-ting kit-8(CCK-8) assay, 4,6-diamidino-2-phenylindole(DAPI) staining, and flow cytometry were used to detect the effects of total saponins of Panacis Majoris Rhizoma on cell viability, morphology, cell cycle and apoptosis of HeLa cells. Western blot was used to detect the expression of apoptosis-related proteins B cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved caspase-9, and cleaved caspase-3, autophagy-related proteins Beclin-1 and SQSTM1(p62), and the proteins related to the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) and mitogen-activated protein kinase(MAPK) signaling pathways. It was found that the yield and saponin content of total saponins from Rhizoma Panacis Majoris were 6.3% and 78.3%, respectively. Total saponins from Rhizoma Panacis Majoris could significantly inhibit the proliferation(P<0.001), effect the nuclear morphology, block the G_0/G_1 cycle, and induce cell apoptosis in HeLa cells with a concentration-dependent manner. In addition, total saponins from Rhizoma Panacis Majoris up-regulated the expression of pro-apoptotic proteins Bax, cleaved caspase-9, and cleaved caspase-3, and autophagy-related protein p62(P<0.05), while down-regulated the expression of anti-apoptotic protein Bcl-2 and autophagy-related protein Beclin-1(P<0.01). Total saponins from Rhizoma Panacis Majoris could promote the expression of p-p38/p38, p-Jun N-terminal kinase(JNK)/JNK, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR proteins in PI3K/Akt/mTOR and MAPK signaling pathways(P<0.05). In contrast, the effect on p-ERK/ERK expression was not obvious. Therefore, total saponins from Rhizoma Panacis Majoris may inhibit autophagy and promote apoptosis of HeLa cells through the activation of the PI3K/Akt/mTOR, c-JNK, and p38 MAPK signaling pathways, which indicates that total saponins from Rhizoma Panacis Majoris may have a potential role in cervical cancer treatment.
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Apoptosis , Autofagia , Proliferación Celular , Rizoma , Saponinas , Neoplasias del Cuello Uterino , Humanos , Saponinas/farmacología , Saponinas/química , Células HeLa , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Autofagia/efectos de los fármacos , Rizoma/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Femenino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Supervivencia Celular/efectos de los fármacosRESUMEN
Four previously unreported triterpenoid saponins named 3ß-hydroxy-23-oxours-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside G) (1), 23-O-acetyl-3ß-hydroxyurs-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside H) (2), ursolic acid 28-O-[α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranosyl] ester (mannioside I) (3), and 3ß-hydroxy-23-oxolup-20(29)-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (mannioside J) (4) were isolated as minor constituents from the EtOAc soluble fraction of the MeOH extract of the leaves of Schefflera mannii along with the known compounds 23-hydroxyursolic acid 28-O-ß-D-glucopyranosyl ester (5), ursolic acid 28-O-ß-D-glucopyranosyl ester (6), pulsatimmoside B (7) betulinic acid 28-O-[α-L-rhamnopyranosyl-(1â4)-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranosyl] ester (8), 23-hydroxy-3-oxo-urs-12-en-28-oic acid (9), hederagenin (10), ursolic acid (11), betulinic acid (12), and lupeol (13). Their structures were elucidated by a combination of 1D and 2D NMR analysis and mass spectrometry. The MeOH extract, the EtOAc and n-BuOH fractions, and some of the isolated compounds were evaluated for their antibacterial activity against four bacteria: Staphylococcus aureus ATCC1026, Staphylococcus epidermidis ATCC 35984, Escherichia coli ATCC10536, and Klepsiella pnemoniae ATCC13882. They were also screened for their antioxidant properties, but no significant results were obtained.
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Antibacterianos , Saponinas , Triterpenos , Triterpenos/química , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Saponinas/química , Saponinas/farmacología , Saponinas/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estructura Molecular , Hojas de la Planta/química , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Araliaceae/químicaRESUMEN
The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.
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Administración Intranasal , Epilepsia , Geles , Mucosa Nasal , Triterpenos , Animales , Administración Intranasal/métodos , Epilepsia/tratamiento farmacológico , Geles/química , Mucosa Nasal/metabolismo , Mucosa Nasal/efectos de los fármacos , Masculino , Triterpenos/administración & dosificación , Triterpenos/farmacocinética , Triterpenos/farmacología , Triterpenos/química , Temperatura , Saponinas/administración & dosificación , Saponinas/química , Saponinas/farmacología , Saponinas/farmacocinética , Química Farmacéutica/métodos , Disponibilidad Biológica , Ratas , Poloxámero/química , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/farmacología , Anticonvulsivantes/químicaRESUMEN
Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug's retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications.
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Micelas , Saponinas , Triterpenos , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Saponinas/farmacología , Saponinas/administración & dosificación , Saponinas/química , Triterpenos/farmacología , Triterpenos/química , Triterpenos/administración & dosificación , Animales , Ratones , Humanos , Línea Celular Tumoral , Nanopartículas/química , Ensayos Antitumor por Modelo de Xenoinjerto , Inhibidores de Puntos de Control Inmunológico/farmacología , Sistemas de Liberación de Medicamentos , FemeninoRESUMEN
The aim of this study is to optimize the extraction process of oat saponins (Os) and to evaluate their antioxidant potential. Single factor experiment, response surface optimization design, and orthogonal test were employed to optimize the process of ultrasonic-assisted extraction of Os, and the optimal extraction conditions were as followed: ethanol volume fraction of 80 %, material-solvent ratio of 1:14, ultrasonic power of 400 W, ultrasonic time of 25 min, extraction temperature of 60â, extraction time of 180 min, and the extraction rate of Os was 0.317 %±0.105 %. Using the method, the crude extract of Os was prepared and its abilities of scavenging radicals in vitro and inhibiting protein oxidation in pork were determined, with ascorbic acid (Vc) as the control. Results revealed that the scavenging ability of Os against DPPH radical, hydroxyl radical (·OH) and superoxide anion (O2-) increased with the concentration of Os. Interestingly, the scavenging abilities of Os against DPPH and O2- were far lower than that of Vc, but its scavenging ability against ·OH was very close to that of Vc, reaching 84.59 % and 96.33 %, respectively. Furthermore, the experiments of pork storage and Fenton oxidation system showed that Os with 0.09-0.72 mg/mL could reduce the production of carbonyl (8.49 %-50.05 %) and the oxidation of total sulfhydryl (1.29 %-25.86 %), and effectively inhibit the oxidation of protein in pork by 7.82 %-22.53 %. The results of this study will provide a theoretical basis for the application of oat saponins as a natural anti-protein oxidant in meat processing and storage.