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1.
Molecules ; 27(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36080237

RESUMO

Bupleurum chinense is an important medicinal plant in China; however, little is known regarding how this plant transcribes and synthesizes saikosaponins under drought stress. Herein, we investigated how drought stress stimulates the transcriptional changes of B. chinense to synthesize saikosaponins. Short-term drought stress induced the accumulation of saikosaponins, especially from the first re-watering stage (RD_1 stage) to the second re-watering stage (RD_2 stage). Saikosaponin-a and saikosaponin-d increased by 84.60% and 75.13%, respectively, from the RD_1 stage to the RD_2 stage. Drought stress also stimulated a rapid increase in the levels of the hormones abscisic acid, salicylic acid, and jasmonic acid. We screened 49 Unigenes regarding the terpenoid backbone and triterpenoid biosynthesis, of which 33 differential genes were significantly up-regulated during drought stress. Moreover, one P450 and two UGTs are possibly involved in the synthesis of saikosaponins, while some transcription factors may be involved in regulating the expression of key enzyme genes. Our study provides a reference for the cultivation of B. chinense and a practical means to ensure the quality (safety and effectiveness) of B. chinense for medicinal use, as well as insights into the modernization of the China Agriculture Research System.


Assuntos
Bupleurum , Ácido Oleanólico , Saponinas , Bupleurum/genética , Secas , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/metabolismo , Raízes de Plantas/genética , Saponinas/metabolismo , Terpenos/metabolismo
2.
Molecules ; 27(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36080314

RESUMO

The leaves of Panax species (e.g., Panax ginseng-PGL, P. quinquefolius-PQL, and P. notoginseng-PNL) can serve as a source for healthcare products. Comprehensive characterization and unveiling of the metabolomic difference among PGL, PQL, and PNL are critical to ensure their correct use. For this purpose, enhanced profiling and chemometrics were integrated to probe into the ginsenoside markers for PGL/PQL/PNL by ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS). A hybrid scan approach (HDMSE-HDDDA) was established achieving the dimension-enhanced metabolic profiling, with 342 saponins identified or tentatively characterized from PGL/PQL/PNL. Multivariate statistical analysis (33 batches of leaf samples) could unveil 42 marker saponins, and the characteristic ginsenosides diagnostic for differentiating among PGL/PQL/PNL were primarily established. Compared with the single DDA or DIA, the HDMSE-HDDDA hybrid scan approach could balance between the metabolome coverage and spectral reliability, leading to high-definition MS spectra and the additional collision-cross section (CCS) useful to differentiate isomers.


Assuntos
Ginsenosídeos , Panax notoginseng , Panax , Saponinas , Biomarcadores/metabolismo , Quimiometria , Cromatografia Líquida de Alta Pressão/métodos , Ginsenosídeos/análise , Espectrometria de Massas/métodos , Panax/química , Folhas de Planta/química , Reprodutibilidade dos Testes , Saponinas/análise
3.
Hematology ; 27(1): 977-986, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36053135

RESUMO

OBJECTIVES: Multiple myeloma (MM) is an incurable plasma cell malignancy associated with poor survival. Novel therapeutic drugs are urgently needed to improve MM therapy and patient outcomes. This study aimed to investigate the effect of formosanin C (FC), a Chinese medicine monomer, on MM in vitro and disclose the underlying molecular mechanism. METHODS: The effect of FC on the viability, proliferation, apoptosis, and autophagy of MM cell lines (NCI-H929 and ARP1) was studied through CCK-8, colony formation, flow cytometry, GFP-LC3, and western blotting assays, respectively. A pharmacological approach and network pharmacology technology were implemented to explore the potential mechanisms of the action of FC on MM cells. RESULTS: FC efficiently suppressed the viability and colony-forming capacity, but promoted the number of autophagic vacuoles with GFP-LC3 localization and the percentage of apoptotic cells in MM cells. Additionally, FC significantly increased the levels of the autophagy-related proteins LC3-Ⅱ and Beclin 1, as well as the apoptosis-related proteins Bax and cleaved caspase-3, but blocked the expression of the proapoptotic protein Bcl-2 in the cells; these effects were reversed by an inhibitor of autophagy, 3-methyladenine. What's more, we found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was involved in the FC-mediated inhibition of MM. Pharmacological inhibition of this pathway dramatically relieved FC-triggered excessive expression of autophagy-related proteins and rescued MM cells from FC-induced apoptosis. CONCLUSION: Our findings indicate that FC exhibits an anti-MM effect by activating cell autophagy through the PI3K/AKT/mTOR signaling pathway.


Assuntos
Mieloma Múltiplo , Proteínas Proto-Oncogênicas c-akt , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteínas Relacionadas à Autofagia/farmacologia , Linhagem Celular Tumoral , Diosgenina/análogos & derivados , Humanos , Mieloma Múltiplo/tratamento farmacológico , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
4.
Ann Palliat Med ; 11(8): 2695-2708, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36064360

RESUMO

BACKGROUND: Ischaemic stroke is a common neurological disease and a leading cause of severe disability and death in developed countries. In most cases, stroke is thought to be a multifactorial disorder or complex trait for which classic patterns of inheritance cannot be shown. Xuesaitong is one of the most commonly used medicines for treating ischemic stroke in China. However, compared to the conventional therapy, the effectiveness and safety of Xuesaitong for ischemic stroke needs to be further systematically reviewed and determined. METHODS: Relevant randomized controlled trials (RCTs) examining the use of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke were identified from databases, including the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science databases. Next, 2 researchers independently extracted information from the included studies, analyzed the data using STATA 15.0 software, and evaluated the quality of the included studies using RevMan 5.3. RESULTS: A total of 17 RCTs (comprising 1,942 patients with ischemic stroke) were included in the meta-analysis. The meta-analysis results showed that the Xuesaitong soft capsule treatment increased patients' total effective rate compared to conventional or other drug treatments, and improved patients' Clinical Severity Score (CSS scores) or Barthel index (BI) score. A further subgroup analysis stratified by different treatment times showed that Xuesaitong soft capsule treatment at 4 and 8 weeks improved CSS scores more than treatment at 2 weeks in patients with ischemic stroke. Additionally, the Xuesaitong soft capsule also significantly improved plasma viscosity, whole-blood viscosity at high and low shear rates, fibrinogen, hematocrit, and the effect on traditional Chinese medicine (TCM) single symptoms or signs in patients with ischemic stroke. DISCUSSION: In summary, compared to conventional or other drug treatments, the Xuesaitong soft capsule treatment was beneficial in improving patients' TCM symptoms (e.g., crooked mouth and tongue, and dizziness) and various indicators. Further, Xuesaitong soft capsule may be a safe and effective drug for the treatment of ischemic stroke. And large-scale randomized clinical trials are needed to further confirm our findings.


Assuntos
Medicamentos de Ervas Chinesas , AVC Isquêmico , Saponinas , Acidente Vascular Cerebral , Cápsulas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Saponinas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico
5.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4411-4417, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046870

RESUMO

This study investigated the anti-ascites effect of the total saponins of Phytolaccae Radix(PRTS) and the mechanism.H22 cell suspension was used(ip) to induce ascites in ICR male mice, and the model mice were randomized into model group, positive drug group(furosemide, 6 mg·kg~(-1)), total extract of Phytolaccae Radix(PRTE) group, and PRTS(1.29 g·kg~(-1)).Another 10 male mice were selected as the blank group.Mice in the blank group and model group were given(ig) normal saline containing 0.5% CMC-Na, and those in the positive drug group, PRTE group, and PRTS group received(ig) corresponding doses of drugs, once a day, for 8 consecutive days.The ascites volume, urine volume, and fecal water content in mice with ascites, serum levels of antidiure-tic hormone(ADH), renin in renin-angiotensin-aldosterone system(RAAS), angiotensin Ⅱ(AngⅡ), and aldosterone(ALD), expression of aquaporin(AQP)1-AQP4 in kidney, expression of AQP1, AQP3 in colon, and expression of phosphatidylinositol 3-kinase/protein kinase B(PI3 K/Akt) pathway-related proteins were detected to explore the anti-ascites mechanism of PRTS.The results showed that the PRTS can increase the urine volume and fecal water content and decrease the ascites volume of ascites mice.Moreover, PRTS significantly reduced the expression of AQP1-AQP4 in kidney and AQP1, AQP3 in colon, serum levels of renin, AngⅡ, ALD, and ADH, and the expression of p-PI3 K and p-Akt in the kidney of ascites mice.PRTS exerts anti-ascites effect by promoting urination and defecation.The mechanism is that it inhibits the activities of RAAS and ADH and suppresses the phosphorylation of PI3 K/Akt signaling pathway, thereby restricting the expression of AQPs in the kidney and colon.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Saponinas , Animais , Aquaporina 1 , Ascite/tratamento farmacológico , Ascite/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Renina/metabolismo , Saponinas/farmacologia , Água/metabolismo
6.
Neuroreport ; 33(15): 656-662, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36126263

RESUMO

OBJECTIVES: To determine the effects of astragaloside IV on cerebral ischemic-reperfusion injury in rats and to explore underlying mechanisms of brain protection. METHODS: Sixty Sprague-Dawley rats were randomized into four groups: Sham, cerebral ischemia-reperfusion (I/R group), I/R+astragaloside IV (I/R+AST-IV group) and I/R+astragaloside IV+PKA kinase inhibitor H-89 (I/R+AST-IV+H-89 group). All I/R rats were subjected to 2 h cerebral ischemia, followed by 24 h reperfusion and scored for neurobehavior. Cerebral infarct volume, pathomorphological changes and brain apoptosis, in addition to changes in expression of Cx36, PKA, Bax and Bcl-2 proteins, were assessed. RESULTS: Astragaloside IV treatment reduced neurobehavioral score and percentage volume of cerebral infarct, reducing pathomorphological injury and brain apoptosis. Expressions of Cx36 and PKA protein were increased and the Bax/Bcl-2 ratio decreased. All astragaloside IV effects were reversed by the PKA inhibitor and H-89. CONCLUSIONS: Astragaloside IV attenuated cerebral I/R injury in rats by increasing Cx36 and PKA protein expression and reducing the Bax/Bcl-2 ratio.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/metabolismo , Infarto Cerebral , Isoquinolinas , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Saponinas , Sulfonamidas , Triterpenos , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo
7.
Pharm Biol ; 60(1): 1781-1789, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36102594

RESUMO

CONTEXT: Polyphyllin II (PPII) is a steroidal saponin isolated from Rhizoma Paridis. It exhibits significant antitumor activity such as anti-proliferation and pro-apoptosis in lung cancer. OBJECTIVE: To explore whether PPII induce autophagy and the relationship between autophagy and apoptosis in non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: The effects of PPII (0, 1, 5, and 10 µM) were elucidated by CCK8 assay, colony formation test, TUNEL staining, MDC method, and mRFP-GFP-LC3 lentivirus transfection in A549 and H1299 cells for 24 h. DMSO-treated cells were selected as control. The protein expression of autophagy (LC3-II, p62), apoptosis (Bcl-2, Bax, caspase-3) and p-mTOR was detected by Western blotting. We explored the relationship between autophagy and apoptosis by autophagy inhibitor CQ (10 µM) and 3-MA (5 mM). RESULTS: PPII (0, 1, 5, and 10 µM) inhibited the proliferation and induced apoptosis. The IC50 values of A549 and H1299 cells were 8.26 ± 0.03 and 2.86 ± 0.83 µM. We found that PPII could induce autophagy. PPII promoted the formation of autophagosome, increased the expression of LC3-II/LC3-I (p < 0.05), while decreased p62 and p-mTOR (p < 0.05). Additionally, the co-treatment with autophagy inhibitors promoted the protein expression of c-caspase-3 and rate of Bax/Bcl-2 (p < 0.05), compared with PPII-only treatment group. Therefore, our results indicated that PPII-induced autophagy may be a mechanism to promote cell survival, although it can also induce apoptosis. CONCLUSIONS: PPII-induced apoptosis exerts its anticancer activity by inhibiting autophagy, which will hopefully provide a prospective compound for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Saponinas , Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/farmacologia , Transdução de Sinais , Esteroides , Serina-Treonina Quinases TOR/metabolismo , Proteína X Associada a bcl-2
8.
Pharm Biol ; 60(1): 1812-1818, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36121248

RESUMO

CONTEXT: Astragaloside IV (AS-IV) is extracted from Astragalus membranaceus (Fisch.) Bunge (Fabaceae). However, its effects on endothelial cell injury remain unclear. OBJECTIVE: To investigate the mechanisms underlying the effects of AS-IV on lipopolysaccharide (LPS)-induced endothelial injury in vitro. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were pre-treated with AS-IV (100 µmol/mL), 4-hydroxy-3-methoxyacetophenone (APO, 10 µmol/mL), N-acetylcysteine (NAC, 50 µmol/mL) and Ac-YVAD-cmk (AC, 5 µmol/mL) for 2 h before 1 µg/mL LPS 24 h exposure. Untreated cells cultured without any exposure were used as controls. Cell viability, reactive oxygen species (ROS) and pyroptosis assays were performed. The pyroptosis related proteins were detected by western blot. RESULTS: The rate in late pyroptosis (Q2-2) of AS-IV (13.65 ± 0.74%), APO (13.69 ± 0.67%) and NAC (15.87 ± 0.46%) groups was lower than the LPS group (21.89 ± 0.66%, p < 0.05), while the rate in early pyroptosis (Q2-4) of AS-IV group (12.00 ± 0.26%) was lower than other groups (p < 0.05). The expression of NOX4, GSDMD, NLRP3, ASC and caspase-1 decreased after AS-IV, NAC or AC intervention (p < 0.05). The ROS production in AS-IV (4664 ± 153.20), APO (4094 ± 78.37), NAC (5103 ± 131.10) and AC (3994 ± 102.50) groups was lower than the LPS (5986 ± 127.30) group, while the mitochondrial BCL2/BAX protein expression ratio increased in AS-IV, APO and NAC groups (p < 0.05). DISCUSSION AND CONCLUSIONS: AS-IV suppressed pyroptosis in LPS-activated HUVECs by inducing ROS/NLRP3-mediated inhibition of the inflammatory response, providing a scientific basis for clinical applications of AS-IV.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Acetilcisteína/farmacologia , Caspase 1/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipopolissacarídeos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2 , Espécies Reativas de Oxigênio/metabolismo , Saponinas , Triterpenos , Proteína X Associada a bcl-2
9.
Chem Biodivers ; 19(9): e202200590, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36070411

RESUMO

Three new furostane saponins, ramofurosides A-C (1-3), and two known saponins, fistulosaponin B (4) and (25R)-26-O-ß-D-glucopyranosyl-1ß,3ß,26-trihydroxyfurosta-5,20(22)-diene-1-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside (5) were isolated from the methanol extract of Allium ramosum seeds. Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for reduction of lipid accumulation in HepG2 cell lines. As a result, compounds 1 and 3 showed a significant reduction in total lipid content by 27.93±3.05 and 27.54±1.68 %, respectively, at a concentration of 100 µM.


Assuntos
Allium , Saponinas , Allium/química , Lipídeos/análise , Metanol , Estrutura Molecular , Extratos Vegetais/química , Saponinas/química , Sementes/química
10.
Front Immunol ; 13: 976968, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119058

RESUMO

Various chemical adjuvants are available to augment immune responses to non-replicative, subunit vaccines. Optimized adjuvant selection can ensure that vaccine-induced immune responses protect against the diversity of pathogen-associated infection routes, mechanisms of infectious spread, and pathways of immune evasion. In this study, we compare the immune response of mice to a subunit vaccine of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) spike protein, stabilized in its prefusion conformation by a proprietary molecular clamp (MERS SClamp) alone or formulated with one of six adjuvants: either (i) aluminium hydroxide, (ii) SWE, a squalene-in-water emulsion, (iii) SQ, a squalene-in-water emulsion containing QS21 saponin, (iv) SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); (v) LQ, neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21, (vi) or LMQ, neutral liposomes containing cholesterol, DOPC, QS21, and 3D6AP. All adjuvanted formulations induced elevated antibody titers which where greatest for QS21-containing formulations. These had elevated neutralization capacity and induced higher frequencies of IFNƔ and IL-2-producing CD4+ and CD8+ T cells. Additionally, LMQ-containing formulations skewed the antibody response towards IgG2b/c isotypes, allowing for antibody-dependent cellular cytotoxicity. This study highlights the utility of side-by-side adjuvant comparisons in vaccine development.


Assuntos
Saponinas , Receptor 4 Toll-Like , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Hidróxido de Alumínio , Animais , Linfócitos T CD8-Positivos , Dissacarídeos , Emulsões , Imunoglobulina G , Interleucina-2 , Lipossomos , Camundongos , Fosforilcolina , Saponinas/farmacologia , Glicoproteína da Espícula de Coronavírus , Esqualeno , Vacinas de Subunidades , Água
11.
Mol Med Rep ; 26(5)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36069235

RESUMO

Platyconic acid A (PA), the active component of Platycodi radix­derived saponin, exerts ameliorating effects on liver fibrosis. Platycodon grandiflorum is used to treat lung disease. Therefore, the present study evaluated the effects of PA on pulmonary fibrosis. Transforming growth factor­ß1 (TGF­ß1) was used to induce MRC­5 cells to establish an in vitro pulmonary fibrosis model. The viability of MRC­5 cells in the presence or absence of TGF­ß1 induction was examined using a Cell Counting Kit­8 assay and the results demonstrated that PA markedly decreased viability of TGF­ß1­induced MRC­5 cells in a dose­dependent manner. Wound healing analysis, immunofluorescent staining and western blotting were performed to determine the levels of cell migration and expression of α­smooth muscle actin and extracellular matrix (ECM)­associated proteins. The results of the present study demonstrated that PA significantly suppressed the migration and ECM deposition of TGF­ß1­induced MRC­5 cells. Furthermore, results obtained from ELISA and western blotting demonstrated that PA exerted suppressive effects on the inflammation of MRC­5 cells following TGF­ß1 stimulation. The mRNA and protein expression levels of protein phosphatase Mg2+/Mn2+­dependent 1A (PPM1A) before and after transfection were assessed using reverse transcription­quantitative PCR and western blotting and the results demonstrated that the mRNA and protein expression levels of PPM1A were significantly decreased following transfection with small interfering RNA targeting PPM1A. Moreover, following PPM1A knockdown, PA significantly inhibited the proliferation, migration, inflammation and ECM deposition of TGF­ß1­induced MRC­5 cells via activation of the SMAD/ß­catenin signaling pathway. In conclusion, PA activated PPM1A to ameliorate TGF­ß1­elicited lung fibroblast injury via modulating SMAD/ß­catenin signaling.


Assuntos
Fibrose Pulmonar , Saponinas , Proliferação de Células , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Humanos , Inflamação/metabolismo , Pulmão/metabolismo , Proteína Fosfatase 2C/genética , Proteína Fosfatase 2C/metabolismo , Fibrose Pulmonar/metabolismo , RNA Mensageiro/metabolismo , Saponinas/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Triterpenos , Regulação para Cima , beta Catenina/metabolismo
12.
Food Funct ; 13(18): 9208-9225, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36047380

RESUMO

Increasing evidence has been reported regarding phytochemicals, plant secondary metabolites, having therapeutic functions against numerous human diseases. Recently, phytochemicals (flavonoids, polyphenols, terpenoids, alkaloids, saponins, coumarins and so on) have shown promising anti-cancer efficacy with their distinct advantages of high efficiency and low toxicity. They regulate programmed cell death (apoptosis, pyroptosis, and autophagy), migration and senescence-related signaling pathways of cancer via the modulation of reactive oxygen species (ROS), mitogen activated protein kinase (MAPK) pathway, deleted in liver cancer 1 (DLC1), nuclear factor κ light-chain-enhancer of activated B cell (NF-κB) pathways and glycolytic enzymes. Here, we review the molecular mechanisms by which phytochemicals prevent the development of cancer. Furthermore, phytochemicals combined with chemotherapeutic agents could target the crosstalk among multiple signal cascades to block chemoresistance and attenuate carcinogenic properties, and can be considered as a novel and potential therapeutic strategy. Our review highlights that the mechanisms and promising applications are required to be understood to decisively establish the anti-cancer efficacy of natural phytochemicals.


Assuntos
Alcaloides , Neoplasias , Saponinas , Cumarínicos , Proteínas Ativadoras de GTPase , Humanos , Proteínas Quinases Ativadas por Mitógeno , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Polifenóis , Espécies Reativas de Oxigênio/metabolismo , Terpenos , Proteínas Supressoras de Tumor
13.
Molecules ; 27(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36080144

RESUMO

Due to their particular structural characteristics, the extraction and isolation of saponins from plants present a serious challenge. In this study, specific extraction protocols were first implemented to extract the secondary metabolites from Astragalus hamosus and, more precisely, the saponins. Subsequent purification of the extracts was based on a single chromatographic technique, high-performance thin-layer chromatography, applying two development systems: a one-step system that separated molecules according to their polarity and a multiple development system that made it possible to detect the triterpenoid saponins, azukisaponin or soyasapogenol at a retarded Rf of 0.2. The difficulties of detecting the Astragalus hamosus saponins encountered during the extraction and purification of the extracts have been highlighted and the strategy carried out to isolate the saponins has been discussed.


Assuntos
Astrágalo (Planta) , Saponinas , Triterpenos , Astrágalo (Planta)/química , Cromatografia em Camada Delgada/métodos , Extratos Vegetais/química , Saponinas/química , Triterpenos/química
14.
Oxid Med Cell Longev ; 2022: 3617086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36132224

RESUMO

Heart failure occurs because of various cardiovascular pathologies, such as coronary artery disease or cardiorenal syndrome, eventually reaching end-stage disease. Various factors contribute to cardiac structural or functional changes that result in systolic or diastolic dysfunction. Several studies have confirmed that the key factor in heart failure progression is myocardial cell death, and mitophagy is the major mechanism regulating myocardial cell death in heart failure. The clinical mechanisms of heart failure are well understood in practice. However, the essential role of mitophagic regulation in heart failure has only recently received widespread attention. Receptor-mediated mitophagy is involved in various mitochondrial processes like oxidative stress injury, energy metabolism disorders, and calcium homeostasis, which are also the main causes of heart failure. Understanding of the diverse regulatory mechanisms in mitophagy and the complexity of its pathophysiology in heart failure remains incomplete. Related studies have found that various natural medicinal plants and active ingredients, such as flavonoids and saponins, can regulate mitophagy to a certain extent, improve myocardial function, and protect myocardial cells. This review comprehensively covers the relevant mechanisms of different types of mitophagy in regulating heart failure pathology and controlling mitochondrial adaptability to stress injury. Further, it explores the relationship between mitophagy and cardiac ejection dysfunction. Natural medicinal plant-targeted regulation strategies and scientific evidence on mitophagy were provided to elucidate current and potential strategies to apply mitophagy-targeted therapy for heart failure.


Assuntos
Insuficiência Cardíaca , Plantas Medicinais , Saponinas , Cálcio/metabolismo , Flavonoides/metabolismo , Insuficiência Cardíaca/patologia , Homeostase , Mitofagia/fisiologia , Miócitos Cardíacos/metabolismo
15.
Biomed Pharmacother ; 153: 113404, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076531

RESUMO

Cone cell-enriched macular degeneration is a major cause of functional vision deterioration. Astragaloside IV (Asg IV), an active triterpenoid saponin component with properties of anti-oxidative and anti-apoptotic damage, which benefit retinal tissue and capillaries. But, the nutraceutical therapeutic effects on functional vision have not been fully evaluated. In this study, mice were administrated to high-intensity light exposure after either receiving a vehicle or Asg IV (0.05, 0.5, and 50 mg/kg, BID). During this time, their spatial-visual performance, visual acuity (VA), and visual contrast sensitivity function (VCSF) were measured using the behavioral optomotor reflex method. Morphological changes in the retina were determined by histological examination. High energy light-evoked visual damage was confirmed by the loss in structural tissue integrity in the retina accompanied by a decline in both VA and VCSF, whereas the retina tissue exhibited loss of cone cell density and severe cone-specific opsin misplacement. In contrast, prophylactic oral Asg IV (0.5, and 50 mg/kg, BID)-treated exerted protective and improvement effects against light-evoked deterioration of functional vision. Asg IV treatment significantly improved the thresholds of VA and VCSF. In particular, Asg IV (50 mg/kg, BID) modulated and increased the survival of the photoreceptors, especially the cone cells, which targeted and enhanced the high spatial frequency-characterized VCSF. In contrast, the cellular protective effect of Asg IV (50 mg/kg, BID) on photoreceptors was significantly reversed by synchronous injection of a glucocorticoid receptor (GR) antagonist (mifepristone). This study demonstrated the major neuroretina-protective effect and functional vision-improving effect of Asg IV in vivo.


Assuntos
Degeneração Retiniana , Saponinas , Triterpenos , Animais , Modelos Animais de Doenças , Camundongos , Células Fotorreceptoras Retinianas Cones/patologia , Saponinas/farmacologia , Saponinas/uso terapêutico , Triterpenos/farmacologia , Triterpenos/uso terapêutico
16.
Acta Virol ; 66(3): 197-205, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36029082

RESUMO

Vaccination is one of the basic strategies in the fight against foot-and-mouth disease (FMD) in endemic regions. Today, commercially available FMD vaccines are prepared with inactive whole virion, which has low immunogenicity. Therefore, considerable effort has been devoted to finding novel adjuvants. Although mineral oils are among the most common adjuvants, it is still difficult to provide a long-term and robust immune response. Combined adjuvant systems are currently being studied to solve the problem. Saponins and CpG-ODNs have been shown to increase the immune response to vaccines individually in various studies. In this study, the effect of different adjuvants and their combinations (Quil-A, E. coli DNA, and MontanideTM ISA 206) on total and neutralizing antibody response in sheep was investigated. According to the results, the Quil-A group induced the highest antibody level, followed by the combination of Quil-A and the E. coli DNA group. The group containing E. coli DNA also caused a higher antibody response than the group containing only MontanideTM ISA 206 for certain days of sampling. These affordable alternatives of saponin and CpG sources can be used individually to increase the potency of the FMD vaccine for mass vaccinations of sheep. Keywords: foot-and-mouth disease; vaccine; adjuvant; Quil-A; E. coli DNA; combination of adjuvants.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Saponinas , Vacinas Virais , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , DNA , Escherichia coli/genética , Febre Aftosa/prevenção & controle , Vírus da Febre Aftosa/genética , Minerais , Óleos , Saponinas de Quilaia , Ovinos , Vacinação/veterinária
17.
J Ethnopharmacol ; 298: 115605, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35973627

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum sisymbriifolium Lam., is used in Paraguayan folk medicine claiming antihypertensive and diuretic properties. AIM OF THE STUDY: This study aimed to determine the influence of chronic oral administration of the crude root extract and saponins obtained from S. sisymbriifolium Lam., on the blood pressure of male and female rats with hypertension induced by L-NAME, and its consequences on diuresis, the body weight, blood glucose, and level of serum parameters of liver and kidney functionality. MATERIALS AND METHODS: Wistar rats were randomly divided into seven male, and seven female groups (8 animals each), which received as 6-week pretreatment, 0.9% saline solution (two groups; 0.1mL/10 g of b.w.), L-arginine (100.0 mg/kg/day), enalapril (15.0 mg/kg/day), crude extract (CESs 100.0 mg/kg/day), and saponin purified fraction (1.0, and 10.0 mg/kg/day), and treated with L-NAME (20 mg/kg/day/i.p.) twice, 1, and 6 h after pre-treatment. The animals' body weight, glycemia, and blood pressure were recorded weekly, while serum, hepatic, renal, and histological parameters were analyzed at the end of 6-week of treatment. RESULTS: A protective effect of CESs (100.0 mg/kg/day), and saponins (1.0, and 10.0 mg/kg/day) against hypertension induced by L-NAME was verified in the systolic, diastolic, and mean blood pressure values, which were significantly lower than the positive L-NAME-hypertensive control group (male and female) at the end of the 6-week treatment. Also, pretreatment with enalapril (15.0 mg/kg/day) induced an efficient protective activity, which validates the method used. Likewise, the volume of urine, creatinine, uric acid, urea, and electrolyte excretion was enhanced at the end of 6-week of treatment in concordance with the reduction in serum level of the same parameters, compatible with the improvement of the diuretic activity. The glycemia, body weight, heart rate, and functional hepato-renal parameters were not modified after a 6-week of treatment, in comparison to the control group, indicating relatively acceptable harmless properties of CESs and saponins. Interestingly, the HDL level in females was increased in contrast to male rats by chronic saponins treatment when compared with the negative control group. CONCLUSIONS: It can be concluded that either the increment in blood pressure (systolic, diastolic, and median) or cardiorenal remodeling effects in male and female rats submitted to L-NAME-induced hypertensive condition, were prevented and well-preserved without a significant variation during a period of 6-week of pretreatment with CESs and saponins pretreatments. Likewise, an important diuretic effect was revealed after this period of treatment.


Assuntos
Hipertensão , Saponinas , Solanum , Animais , Anti-Hipertensivos , Pressão Sanguínea , Peso Corporal , Diuréticos/farmacologia , Enalapril , Feminino , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Extratos Vegetais , Ratos , Ratos Wistar , Saponinas/farmacologia , Saponinas/uso terapêutico
18.
Drug Deliv ; 29(1): 2743-2750, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35999702

RESUMO

Liposomes have been widely used for targeted drug delivery, but the disadvantages caused by cholesterol limit the application of conventional liposomes in cancer treatment. The compatibility basis of couplet medicines and the compatibility principle of the traditional Chinese medicine principle of 'monarch, minister, assistant and guide' are the important theoretical basis of Chinese medicine in the treatment of tumor and the important method to solve the problem of high toxicity. In this study, the active ingredients of the couplet medicines Platycodon grandiflorum and Glycyrrhiza uralensis were innovatively utilized, and glycyrrhizic acid (GA) was encapsulated in liposomes constructed by mixing saponin and lecithin, and cholesterol was replaced by platycodin and ginsenoside to construct saponin liposomes (RP-lipo) for the drug delivery system of Chinese medicine. Compared with conventional liposomes, PR-lipo@GA has no significant difference in morphological characteristics and drug release behavior, and also shows stronger targeting of lung cancer cells and anti-tumor ability in vitro, which may be related to the pharmacological properties of saponins themselves. Thus, PR-lipo@GA not only innovatively challenges the status of cholesterol as a liposome component, but also provides another innovative potential system with multiple functions for the clinical application of TCM couplet medicines.


Assuntos
Glycyrrhiza uralensis , Neoplasias Pulmonares , Platycodon , Saponinas , Ácido Glicirrízico/farmacologia , Humanos , Lipossomos , Neoplasias Pulmonares/tratamento farmacológico , Raízes de Plantas , Saponinas/farmacologia
19.
Fish Shellfish Immunol ; 128: 67-73, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35921931

RESUMO

The sea cucumber Apostichopus japonicus is one of the most dominant and economically important aquaculture species in China. Saponin, which possesses notable biological and pharmacological properties, is a key determinant of the nutritional and health value of A. japonicus. In the present study, we amplified the full-length cDNA of a phosphomevalonate kinase (PMK) gene (named AjPMK) using rapid amplification of cDNA ends (RACE). Subsequently, we engineered a recombinant AjPMK (rAjPMK) protein and assessed its enzymatic activity by enzyme-linked immunosorbent assay (ELISA). Proteins that interact with rAjPMK were screened and identified via pull-down assay combined with liquid chromatography with tandem mass spectrometry (LC-MS/MS). We found that the full-length cDNA of AjPMK contained 1354 bp and an open reading frame (ORF) of 612 bp. The AjPMK protein was predicted not to contain a signal peptide but to contain a phosphonolate kinase domain seen in higher eukaryotes and a P-loop with a relatively conserved nucleoside triphosphate hydrolase domain. The molecular weight of the AjPMK protein was estimated to be 23.81 kDa, and its isoelectric point was predicted to be 8.72. Phylogenetic analysis showed that AjPMK had a closer evolutionary relationship with genes from starfish than with those of other selected species. Besides, we found that rAjPMK synthesized mevalonate-5-diphosphate, interacted either directly or indirectly with crucial pattern recognition receptors (PRRs) and was regulated by immune-related processes, including antioxidative reactions, stress resistance responses and enzyme hydrolysis. Moreover, AjPMK also interacted with farnesyl pyrophosphate synthase, an enzyme reported to be involved in saponin biosynthesis. Together, our findings implied that AjPMK may be directly involved in saponin biosynthesis and the regulation of various innate immune processes.


Assuntos
Saponinas , Pepinos-do-Mar , Stichopus , Sequência de Aminoácidos , Animais , Sequência de Bases , Cromatografia Líquida , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Difosfatos , Hidrolases/genética , Hidrolases/metabolismo , Imunidade Inata/genética , Ácido Mevalônico/análogos & derivados , Nucleosídeos , Fosfotransferases (Aceptor do Grupo Fosfato) , Filogenia , Sinais Direcionadores de Proteínas/genética , Pepinos-do-Mar/genética , Espectrometria de Massas em Tandem
20.
Chem Biodivers ; 19(9): e202100961, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35979749

RESUMO

Herba Patriniae (HP) is widely used as a medicinal and edible material in China. Besides food value, HP attracts more attention due to its medicinal potential. Patrinia villosa Juss. (PV) and Patrinia scabiosaefolia Fisch. (PS) are the two species origins of HP. These two of HP show different effects on cell proliferation, migration, angiogenesis and anti-diabetic. As we have previously reported, PV and PS show significant differences on their anti-inflammatory ability in the same experimental model. Comparing the ingredient profiles of two different sources will not only facilitate the understanding of their medicinal effects, but also help the development and research of new activities. However, still now, there is no systematic and detailed study to compare the components of PV and PS. In present study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed to achieve a high-throughput qualitative and thorough analysis of the chemical composition spectrum of HP. A total of 164 compounds were identified, among these compounds, 127 compounds were identified from PV, and 107 compounds were identified from PS. Most of the chemical components was discovered for the first time. Flavonoids, saponins, terpenoids and organic acids, as the main ingredients in PV and PS were 45.45 %vs 28.46 %, 12.61 % vs. 32.09 %, 14.33 % vs. 22.38 % and 14.58 % vs. 6.79 %, respectively. Flavonoids are the main components of PV, while PS is rich in saponins. PV and PS were classified into two groups by principal component analysis (PCA) and screened out the main molecular differences responsible by orthogonal partial least squares discriminant analysis (OPLS-DA). All the results will be a guide for the quality control, functional activity research, or better clinic use based on the ingredients profile between these two species. Besides, this first study on ingredients profile of two species origins will be beneficial for potential and best resources utilization of both PV and PS.


Assuntos
Patrinia , Saponinas , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Análise Discriminante , Flavonoides/química , Análise dos Mínimos Quadrados , Patrinia/química , Espectrometria de Massas em Tandem/métodos , Terpenos
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