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1.
Am J Chin Med ; 48(6): 1331-1351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32907361

RESUMO

Panax notoginseng is the most widely used Chinese medicinal herb for the prevention and treatment of ischemic diseases. Its main active ingredients are saponins, including ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1, among others. This review provides an up-to-date overview on the pharmacological roles of P. notoginseng constituents in cerebral ischemia. The saponins of P. notoginseng induce a variety of pharmacological effects in the multiscale mechanisms of cerebral ischemic pathophysiology, including anti-inflammatory activity, reduction of oxidative stress, anti-apoptosis, inhibition of amino acid excitotoxicity, reduction of intracellular calcium overload, protection of mitochondria, repairing the blood-brain barrier, and facilitation of cell regeneration. Regarding cell regeneration, P. notoginseng not only promotes the proliferation and differentiation of neural stem cells, but also protects neurons, endothelial cells and astrocytes in cerebral ischemia. In conclusion, P. notoginseng may treat cerebrovascular diseases through multiple pharmacological effects, and the most critical ones need further investigation.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Panax notoginseng/química , Fitoterapia , Saponinas/farmacologia , Saponinas/uso terapêutico , Aminoácidos/toxicidade , Animais , Anti-Inflamatórios , Antioxidantes , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Cálcio/metabolismo , Autorrenovação Celular/efeitos dos fármacos , Depuradores de Radicais Livres , Ginsenosídeos/isolamento & purificação , Humanos , Fármacos Neuroprotetores , Estresse Oxidativo/efeitos dos fármacos , Saponinas/isolamento & purificação
2.
Environ Sci Pollut Res Int ; 27(32): 40787-40794, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32677014

RESUMO

Studies from our group and others have reported that 30 mW/cm2 microwave could damage the structures of rat hippocampus, as well as impair the neuronal functions. The neuroprotective effects of astragaloside, purified from Astragalus membranaceus, have been demonstrated in animal models of neurodegenerative diseases. In this study, we found that 30 mW/cm2 microwave impaired spatial learning and memory ability in rats, while astragaloside could significantly alleviate the injuries. The pathological analysis also showed that astragaloside protected neurons from microwave-induced damages, such as mitochondrial swelling and cavitation, rough endoplasmic reticulum swelling and dilation, synaptic gap disappearing, and vesicle aggregation. Moreover, microwave-induced structural damage of synapse resulted in downregulation of acetylcholine, an important neurotransmitter for information transmission, while astragaloside could protect the structure of synapse, as well as restore the acetylcholine level in rat hippocampus. Furthermore, astragaloside also accelerated the recovery of brain electroencephalogram (EEG) after microwave exposure, indicating that astragaloside could promote the normalization of neuronal functions. In conclusion, astragaloside protected the morphological structures and restored acetylcholine level in rat hippocampus, which could improve brain functions via normalizing brain EEG. Therefore, astragaloside might be a promising candidate to treat microwave-induced injuries of central nervous system (CNS).


Assuntos
Saponinas , Triterpenos , Acetilcolina , Animais , Encéfalo , Eletroencefalografia , Memória , Micro-Ondas , Ratos , Saponinas/farmacologia , Triterpenos/farmacologia
3.
Life Sci ; 257: 118040, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622943

RESUMO

AIMS: Timosaponin AIII (TAIII), an active component with anti-tumor activity from Anemarrhena asphodeloides Bunge, can induce both autophagy and apoptosis of cancer cells. The present study aimed to reveal the promoting or inhibiting role of TAIII-induced autophagy on TAIII-induced apoptosis, to determine the respective upstream signaling pathways for TAIII-induced autophagy and apoptosis; and to observe the therapeutic potential of TAIII in human non-small cell lung cancer in vivo. METHODS AND MATERIALS: WST-1 assay was used to determine the effect of TAIII on cell growth and proliferation. Apoptosis was detected by DAPI staining and flow cytometry. Autophagy was verified by immunofluorescence and transmission electron microscopy. Western blot was used to determine the levels of protein expression. Furthermore, the anti-tumor activity of TAIII was observed in nude mice. KEY FINDINGS: TAIII at high concentrations from 10 µM to 30 µM induced both autophagy and apoptosis in human non-small cell lung cancer cells in a time- and concentration-dependent manner. TAIII at low concentration (1 µM) only induced autophagy. The AMP-activated protein kinase (AMPK) signaling pathway was identified to be responsible for TAIII-induced autophagy both at high or low concentrations. The MAPK/Erk1/2 signaling pathway was identified to be responsible for TAIII-induced apoptosis at the high concentration (20 µM). TAIII-induced autophagy protected cancer cells from apoptosis, and combination of TAIII and autophagy inhibitor showed higher anti-cancer activity.


Assuntos
Autofagia/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Saponinas/farmacologia , Esteroides/farmacologia , Células A549 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antineoplásicos , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Saponinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esteroides/metabolismo
4.
Biochim Biophys Acta Bioenerg ; 1861(10): 148251, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32598881

RESUMO

Saponins are a diverse group of secondary plant metabolites, some of which display hemolytic toxicity due to plasma membrane permeabilization. This feature is employed in biological applications for transferring hydrophilic molecules through cell membranes. Widely used commercial saponins include digitonin and saponins from soap tree bark, both of which constitute complex mixtures of little definition. We assessed the permeabilization power of pure saponins towards cellular membranes in an effort to detect novel properties and to improve existing applications. In a respirometric assay, we characterized half-maximal permeabilization of the plasma membrane for different metabolites, of the mitochondrial outer membrane for cytochrome C and the full solubilization of mitochondrial inner membrane protein complexes. Beyond the complete list as repository for the field, we highlight several findings with direct applicability. First, we identified and validated α-chaconine as alternative permeabilization agent in respirometric assays of cultured cells and isolated synaptosomes, superior to digitonin in its tolerability for mitochondria. Second, we identified glycyrrhizic acid to form exceptionally small pores impermeable for adenosine diphosphate. Third, in a concentration dependent manner, tomatine proved to be able to selectively permeabilize the mitochondrial outer, but not inner membrane, allowing for novel states in which to determine cytochrome C oxidase activity. In summary, we provide a list of the permeabilization properties of 18 pure saponins. The identification of two saponins, namely tomatine and chaconine, with direct usability in improved or novel cell biological applications within this small subgroup demonstrates the tremendous potential for further functional screening of pure saponins.


Assuntos
Metabolismo/efeitos dos fármacos , Saponinas/farmacologia , Animais , Calorimetria , Permeabilidade da Membrana Celular/efeitos dos fármacos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Células HEK293 , Humanos , Camundongos
6.
Am J Chin Med ; 48(4): 1021-1034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32471314

RESUMO

Codonopsis lanceolata roots have been widely used in Korean cuisine and traditional medicine. This study aimed to investigate the antimetastatic effects of lancemaside A, a major triterpenoid saponin, isolated from the roots of C. lanceolata, in human ovarian cancer cells. Lancemaside A significantly suppressed the migration and invasion and the expression of matrix metalloproteinases (MMPs)-2 and -9 in ovarian cancer A2780 and SKOV3 cells. Treatment with lancemaside A generated reactive oxygen species (ROS) in ovarian cancer cells. However, treatment with anti-oxidant N-acetyl-L-cysteine (NAC) significantly negated the anti-invasive activity of lancemaside A. Additionally, lancemaside A activated p38 MAP kinase, which is mediated by ROS generation. This is the first study, to our knowledge, to reveal that lancemaside A isolated from the roots of C. lanceolata exerts antimetastatic activity through inhibition of MMP expression and cancer cell invasion via activation of the ROS-mediated p38 pathway.


Assuntos
Codonopsis/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias Ovarianas/patologia , Raízes de Plantas/química , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antineoplásicos Fitogênicos , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Humanos , Saponinas/isolamento & purificação , Proteínas Quinases p38 Ativadas por Mitógeno/genética
7.
Food Chem ; 327: 127029, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32450486

RESUMO

Platycodonis Radix, the root of Platycodon grandiflorum (Jacq.) A. DC., is a well-known edible herbal medicine. It is a common vegetable used for the preparation of side dish, kimchi, dessert, and tea. Besides, it has been used to treat respiratory disease including cough, excessive phlegm, and sore throat for a long history. In the past decades, the bioactive components and the pharmacological activities of Platycodonis Radix have been widely investigated. Thereinto, platycodins, the oleanane-type triterpenoid saponins were demonstrated to be the main bioactive components in Platycodonis Radix, and more than 70 platycodins have been identified up to date. This paper mainly reviewed the phytochemistry, pharmacological activities (apophlegmatic, anti-tussive, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, immunomodulatory, cardiovascular protective, and hepatoprotective activities, etc.), toxicology and pharmacokinetics of platycodins isolated from Platycodonis Radix, aiming to promote further investigation on therapeutic potential of these platycodins.


Assuntos
Platycodon/química , Saponinas/química , Saponinas/farmacologia , Animais , Humanos , Fitoterapia , Saponinas/farmacocinética , Saponinas/toxicidade
8.
Chem Biol Interact ; 326: 109141, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32454006

RESUMO

This study was aimed to investigate the cytotoxic potential of a natural compound, progenin III on a broad range of cancer cell lines, including various sensitive and drug-resistant phenotypes. The cytotoxicity, progenin III-induced autophagic, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). Spectrophotometric analysis of caspases activity was performed using caspase-Glo assay. Flow cytometry was applied for cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). Progenin III and the reference molecule, doxorubicin exerted cytotoxic effects towards the 18 cancer cell lines tested including animal and human cell lines. The IC50 values obtained ranged from 1.59 µM (towards CCRF-CEM leukemia cells) to 31.61 µM (against the BRAF-V600E homozygous mutant SKMel-28 melanoma cells) for progenin III. Normal sensitivity was achieved with CEM/ADR5000 cells and HCT116p53-/- adenocarcinoma cells respectively compared to their sensitive congeners CCRF-CEM cells and HCT116 p53+/+ cells. Progenin III induced apoptosis in CCRF-CEM cells mediated by caspases 3/7 activation, MMP alteration and increase ROS production, and otherwise autophagy and necroptosis. Progenin III is a potential anticancer molecule that deserves further investigations to develop a novel drug to combat malignant diseases including refractory cancers.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Saponinas/farmacologia , Espirostanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células HCT116 , Células Hep G2 , Humanos , Melanoma Experimental , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-32348180

RESUMO

The ubiquitous calpains, calpain-1 and -2, play important roles in Ca2+-dependent membrane repair. Mechanically active tissues like skeletal muscle are particularly reliant on mechanisms to repair and remodel membrane injury, such as those caused by eccentric damage. We demonstrate that calpain-1 and -2 are master effectors of Ca2+-dependent repair of mechanical plasma membrane scrape injuries, although they are dispensable for repair/removal of small wounds caused by pore-forming agents. Using CRISPR gene-edited human embryonic kidney 293 (HEK293) cell lines, we established that loss of both calpains-1 and -2 (CAPNS1-/-) virtually ablates Ca2+-dependent repair of mechanical scrape injuries but does not affect injury or recovery from perforation by streptolysin-O or saponin. In contrast, cells with targeted knockout of either calpain-1 (CAPN1-/-) or -2 (CAPN2-/-) show near-normal repair of mechanical injuries, inferring that both calpain-1 and calpain-2 are equally capable of conducting the cascade of proteolytic cleavage events to reseal a membrane injury, including that of the known membrane repair agent dysferlin. A severe muscular dystrophy in a murine model with skeletal muscle knockout of Capns1 highlights vital roles for calpain-1 and/or -2 for health and viability of skeletal muscles not compensated for by calpain-3 (CAPN3). We propose that the dystrophic phenotype relates to loss of maintenance of plasma membrane/cytoskeletal networks by calpains-1 and -2 in response to directed and dysfunctional Ca2+-signaling, pathways hyperstimulated in the context of membrane injury. With CAPN1 variants associated with spastic paraplegia, a severe dystrophy observed with muscle-specific loss of calpain-1 and -2 activity identifies CAPN2 and CAPNS1 as plausible candidate neuromuscular disease genes.


Assuntos
Calpaína/deficiência , Membrana Celular/enzimologia , Músculo Esquelético/enzimologia , Distrofia Muscular do Cíngulo dos Membros/enzimologia , Distrofia Muscular Animal/enzimologia , Animais , Proteínas de Bactérias/farmacologia , Sinalização do Cálcio , Calpaína/genética , Membrana Celular/efeitos dos fármacos , Membrana Celular/patologia , Modelos Animais de Doenças , Disferlina/deficiência , Disferlina/genética , Feminino , Células HEK293 , Humanos , Masculino , Camundongos Knockout , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/patologia , Saponinas/farmacologia , Índice de Gravidade de Doença , Estreptolisinas/farmacologia
10.
Chin J Nat Med ; 18(3): 161-168, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245585

RESUMO

The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins (SIRTs), Forkhead box O (FoxO), Sterol-regulatory element-binding proteins (SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.


Assuntos
Fígado Gorduroso Alcoólico/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fitoterapia , Alcaloides/farmacologia , Animais , Citocinas/metabolismo , Dislipidemias , Flavonoides/farmacologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Insulina/metabolismo , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Saponinas/farmacologia , Sirtuínas/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Hormônios Tireóideos/metabolismo
11.
Adv Exp Med Biol ; 1221: 461-470, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32274722

RESUMO

Heparanase regulates multiple biological activities that enhance tumor growth and metastatic spread. Heparanase cleaves and degrades heparan sulfate (HS), a key structural component of the extracellular matrix that serves as a barrier to cell invasion and also as a reservoir for cytokines and growth factors critical for tumor growth and metastasis. For this reason, heparanase is an attractive target for the development of novel anti-cancer therapies. Pixatimod (PG545), a heparanase inhibitor, has shown promising results in the treatment of multiple tumor types. PG545 offers a diversity of mechanisms of action in tumor therapy that include angiogenic inhibition, inhibition of growth factor release, inhibition of tumor cell migration, tumor cell apoptosis, activation of ER stress response, dysregulation of autophagy, and NK cell activation. Further investigation into the role that heparanase and its inhibitors play in tumor therapy can lead to the development of effective tumor therapies.


Assuntos
Glucuronidase/antagonistas & inibidores , Heparitina Sulfato/imunologia , Heparitina Sulfato/farmacologia , Neoplasias/tratamento farmacológico , Saponinas/imunologia , Saponinas/farmacologia , Humanos , Neoplasias/enzimologia , Neoplasias/imunologia , Neoplasias/patologia
12.
Adv Exp Med Biol ; 1221: 539-565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32274726

RESUMO

Pixatimod is an inhibitor of heparanase, a protein which promotes cancer via its regulation of the extracellular environment by enzymatic cleavage of heparan sulfate (HS) and non-enzymatic signaling. Through its inhibition of heparanase and other HS-binding signaling proteins, pixatimod blocks a number of pro-cancerous processes including cell proliferation, invasion, metastasis, angiogenesis and epithelial-mesenchymal transition. Several laboratories have found that these activities have translated into potent activity using a range of different mouse cancer models, including approximately 30 xenograft and 20 syngeneic models. Analyses of biological samples from these studies have confirmed the heparanase targeting of this agent in vivo and the broad spectrum of anti-cancer effects that heparanase blockade achieves. Pixatimod has been tested in combination with a number of approved anti-cancer drugs demonstrating its clinical potential, including with gemcitabine, paclitaxel, sorafenib, platinum agents and an anti-PD-1 antibody. Clinical testing has shown pixatimod to be well tolerated as a monotherapy, and it is currently being investigated in combination with the anti-PD-1 drug nivolumab in a pancreatic cancer phase I trial.


Assuntos
Antineoplásicos/farmacologia , Glucuronidase/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Saponinas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/patologia , Saponinas/uso terapêutico
13.
Nutr Metab Cardiovasc Dis ; 30(5): 829-842, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32278611

RESUMO

BACKGROUND AND AIM: The transcription factor GATA-4 plays an important role in myocardial protection. Astragaloside IV (Ast-IV) was reported with the effects on improving cardiac function after ischemia. In this study, we explored how Ast-IV interacts with GATA-4 to protect myocardial cells H9c2 against Hypoxia/Reoxygenation (H/R) stress. METHODS AND RESULTS: H9c2 cells were cultured under the H/R condition. Various cell activity and morphology assays were used to assess the rates of apoptosis and autophagy. In these H/R injured H9c2 cells, increased apoptosis (P < 0.01) and autophagosome number (P < 0.01) were observed, and the addition of Ast-IV ameliorated this tendency. Mechanistically, we used the RT-qPCR and Western blot to evaluate the expressions of various molecules. The results showed that Ast-IV treatment upregulated gene expression of GATA-4 (P < 0.01) and the survival factors (Bcl-2, P < 0.05; p62, P < 0.01), but suppressed apoptosis and autophagy related genes (PARP, Caspase-3, Beclin-1, and LC3-II; All P < 0.01). Furthermore, overexpressing of GATA-4 by its agonist phenylephrine can also protect H/R injured H9c2 cells, and the addition of Ast-IV further enhanced this protection of GATA-4. In contrast, silencing GATA-4 expression abolished the H/R protection of Ast-IV, which demonstrated that the myocardial protection of Ast-IV is mediated by GATA-4. Lastly, along with GATA overexpression, enhanced interactions between Bcl-2 and Beclin-1 were detected by Chromatin immunoprecipitation (P < 0.01). CONCLUSION: Ast-IV rescued the H/R injury induced apoptosis and autophagy in H9c2 cells. Ast-IV treatment can stimulate the overexpression of GATA-4, and further enhanced the myocardial protection effect of GATA-4.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Fator de Transcrição GATA4/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Hipóxia Celular , Linhagem Celular , Citoproteção , Fator de Transcrição GATA4/genética , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Transdução de Sinais , Regulação para Cima
14.
Poult Sci ; 99(4): 1921-1927, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241472

RESUMO

The present study aimed to evaluate the immunopotentiating effect of plant-derived soyasaponin and its immunogenicity in chickens challenged with Newcastle disease virus (NDV). Soyasaponin was extracted from soybean seeds and detected using the phytochemical tests, followed by quantification through the dry-weight method. One-day-old broiler chicks (n = 90) were divided into 3 groups, named as A, B, and C. Group A birds were orally administrated with soyasaponin (5 mg/kg), followed by immunization with inactivated ND vaccine intramuscularly (IM), whereas group B birds were vaccinated with inactivated ND vaccine alone. Group C birds were kept unvaccinated. A booster dose on day 21 was also administered IM to group A and B birds. At day 35, all 3 groups were challenged with NDV. To determine the immunogenicity potential of soyasaponin, antibody titer was measured using the hemagglutination inhibition test before and after the NDV challenge. Histochemical examination was performed to determine the pathological changes associated with NDV infection. Foam formation and hemolytic activity confirmed the presence of saponin in soya bean extract. Group A birds showed a higher antibody response compared with group B and C birds. The disease challenge study showed that soyasaponin-adjuvanted NDV vaccine provided complete protection to group A birds against ND. Moreover, no side effects of soyasaponin were observed on the growth performance of birds during the experiment. Therefore, we can conclude that soyasaponin is a potential immunogenic agent and therefore could be a promising candidate to launch a protective humoral response against ND in chickens.


Assuntos
Galinhas , Imunidade Humoral/efeitos dos fármacos , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Substâncias Protetoras/farmacologia , Saponinas/farmacologia , Vacinas Virais/administração & dosagem , Administração Oral , Animais , Substâncias Protetoras/administração & dosagem , Saponinas/administração & dosagem , Soja/química , Vacinas de Produtos Inativados/administração & dosagem
15.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1418-1422, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281356

RESUMO

Polyphyllin D is a steroid saponin monomer in Polyphyllin, with antibacterial, analgesic, sedative, anti-tumor and other pharmacological effects, but is rarely reported in pancreatic cancer. This study detected apoptosis-relevant indicators, in order to explore the effect of polyphyllin D on the proliferation and apoptosis of human pancreatic cancer Panc-1 cells and relevant mechanisms of action. After pancreatic cancer Panc-1 cells were treated with polyphyllin D(0, 1, 2, 3, 4, 5 µg·µL~(-1)) for 24, 48 and 72 hours, CCK-8 method was used to detect the effect of polyphyllin D on the proliferation of pancreatic cancer Panc-1 cells. Flow cytometry was used to detect cell cycle and changes in mitochondrial membrane potential(MMP). The apoptosis was detected by Annexin V-FITC/PI staining, and Western blot was used to detect the protein expressions of cytochrome C(Cyto C), Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9. The results indicated that compared with the control group, polyphyllin D could inhibit the proliferative activity of Panc-1 cells in a time and concentration-dependent manner. Flow cytometry results showed that polyphyllin D could block the cells in S and G_2/M phase in a concentration manner, the MMP of the cells was significantly reduced, and the apoptosis rate increased with the concentration of polyphyllin D. Western blot results showed that polyphyllin D could concentration-dependently up-regulate the protein expression levels of Bax, Cyto C, cleaved caspase-3 and cleaved caspase-9, and down-regulate the protein expression level of Bcl-2. The above findings suggested that polyphyllin D could effectively inhibit the proliferation of Panc-1 cells, and its mechanism may be related to the blocking of cell growth cycle and the apoptosis induced by mitochondrial pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose , Diosgenina/análogos & derivados , Neoplasias Pancreáticas/patologia , Saponinas/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Diosgenina/farmacologia , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
16.
Phytomedicine ; 69: 153193, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32120245

RESUMO

BACKGROUND: Although mechanical barriers and modern surgical techniques have been developed to prevent postoperative adhesion formation, high incidence of adhesions still represents an important challenge in abdominal surgery. So far, there has been no available therapeutic drug in clinical practice. PURPOSE: In this study, we explored the efficacy of sodium aescinate (AESS) treatment against postoperative peritoneal adhesions, the potential molecular mechanism was also investigated. STUDY DESIGN AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into 6 groups for the study: the blank, vehicle, positive control and three AESS administration groups (0.5, 1 and 2 mg/kg/d, intravenous administration for 7 days). Adhesions were induced by discretely ligating peritoneal sidewall. An IL-1ß-induced HMrSV5 cell model was also performed to explore possible functional mechanism. RESULTS: The results indicated that the incidence and severity of peritoneal adhesions were significantly lower in the AESS-treated groups than that in the vehicle and positive control group. AESS-treated groups showed that the secretion, activity, and expression of tPA in rat peritoneum were notably increased. The FIB levels in rat plasma were decreased. The immunohistochemical staining analysis demonstrated that collagen I and α-SMA deposition were significantly attenuated in AESS-treated peritoneal tissues. Besides, we found that AESS treatment reduced the protein levels of p-MYPT1. To further explore the mechanisms of AESS, both activator and inhibitors of RhoA/ROCK pathway were employed in this study. It was found that AESS-induced up-regulation of tPA was reversed by activator of ROCK, but the effects of ROCK inhibitors were consistent with AESS. CONCLUSION: Taken together, the findings of in vivo and in vitro experiments proved that AESS could significantly suppress postoperative peritoneal adhesion formation through inhibiting the RhoA/ROCK signaling pathway. Our researches provide important pharmacological basis for AESS development as a potential therapeutic agent on peritoneal adhesions.


Assuntos
Doenças Peritoneais/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Saponinas/farmacologia , Triterpenos/farmacologia , Proteínas rho de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Linhagem Celular , Colágeno Tipo I/metabolismo , Fibrinogênio/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Masculino , Doenças Peritoneais/patologia , Doenças Peritoneais/prevenção & controle , Peritônio/citologia , Peritônio/cirurgia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/prevenção & controle , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Aderências Teciduais
17.
J Nat Med ; 74(3): 591-598, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32200514

RESUMO

Three new steroidal saponins, aspiletreins A-C (1-3), together with 2H-chromen-2-one (4), and α-tocopherol (5), were isolated from whole Aspidistra letreae plants collected in Vietnam. Their structures were elucidated by a combination of spectroscopic analyses, including 1D- and 2D-NMR, IR, and HRESIMS, and by comparison with the reported data in the literature. Compounds 1-3 exhibited moderate cytotoxicities against the LU-1, HeLa, MDA-MB-231, HepG2, and MKN-7 human cancer cell lines, with IC50 values ranging from 7.69 ± 0.40 to 20.46 ± 3.11 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Asparagaceae/química , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Células HeLa , Células Hep G2 , Humanos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Extratos Vegetais/química , Saponinas/química , Vietnã
18.
Phytother Res ; 34(5): 1096-1107, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32197276

RESUMO

Astragaloside III (AS-III) is a triterpenoid saponin contained in Astragali Radix and has potent anti-inflammatory effects on vascular endothelial cells; however, underlying mechanisms are unclear. In this study, we provided the first piece of evidence that AS-III induced phosphorylation of TNF-α converting enzyme (TACE) at Thr735 and enhanced its sheddase activity. As a result, AS-III reduced surface TNFR1 level and increased content of sTNFR1 in the culture media, leading to the inhibition of NF-κB signaling pathway and attenuation of downstream cytokine gene expression. Furthermore, AS-III induced TACE-dependent epidermal growth factor receptor (EGFR) transactivation and activation of downstream ERK1/2 and AKT pathways. Finally, AS-III induced activation of p38. Both TACE activation and EGFR transactivation induced by AS-III were significantly inhibited by p38 inhibitor SB203580. Taken together, we concluded that AS-III activates TACE-dependent anti-inflammatory and growth factor signaling in vascular endothelial cells in a p38-dependent fashion, which may contribute to its cardiovascular protective effect.


Assuntos
Proteína ADAM17/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Saponinas/uso terapêutico , Animais , Humanos , Camundongos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos
19.
J Immunol Res ; 2020: 2714257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149156

RESUMO

Pseudorabies is an important infectious disease of swine, and immunization using attenuated pseudorabies virus (aPrV) vaccine is a routine practice to control this disease in swine herds. This study was to evaluate a saline solution containing ginseng stem-leaf saponins (GSLS) and sodium selenite (Se) as a vaccine adjuvant for its enhancement of immune response to aPrV vaccine. The results showed that aPrV vaccine diluted with saline containing GSLS-Se (aP-GSe) induced significantly higher immune responses than that of the vaccine diluted with saline alone (aP-S). The aP-GSe promoted higher production of gB-specific IgG, IgG1, and IgG2a, neutralizing antibody titers, secretion of Th1-type (IFN-γ, IL-2, IL-12), and Th2-type (IL-4, IL-6, IL-10) cytokines, and upregulated the T-bet/GATA-3 mRNA expression when compared to aP-S. In addition, cytolytic activity of NK cells, lymphocyte proliferation, and CD4+/CD8+ ratio was also significantly increased by aP-GSe. More importantly, aP-GSe conferred a much higher resistance of mice to a field virulent pseudorabies virus (fPrV) challenge. As the present study was conducted in mice, further study is required to evaluate the aP-GSe to improve the vaccination against PrV in swine.


Assuntos
Adjuvantes Imunológicos , Panax/química , Saponinas/farmacologia , Selênio/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Vacinas/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Biomarcadores , Relação CD4-CD8 , Citocinas/metabolismo , Feminino , Expressão Gênica , Imunoglobulina G/imunologia , Camundongos , Vacinas contra Pseudorraiva/imunologia , Saponinas/química , Selênio/química , Soluções , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Suínos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo
20.
Biol Pharm Bull ; 43(3): 463-473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115504

RESUMO

Choline as a quaternary amine nutrient is metabolized to trimethylamine by gut microbiota and subsequently oxidized to circulating trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with liver toxicity and cardiovascular disease. The study was to probe the possible vasoprotective and hepatoprotective effects of total saponins of Gynostemma pentaphyllum (TSGP) in 3% high-choline water-feeding mice. The purified TSGP was obtained with content of 83.0% saponins, and its antioxidant activities were evaluated in vitro. Furthermore, the mice fed with high choline for 8 weeks significantly expressed vascular endothelial dysfunction and liver oxidative stress (p < 0.01 vs. Normal). Administration of TSGP at 400 and 800 mg/kg·body weight (b.w.) significantly lowered the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), endothelin-1 (ET-1) and thromboxane A2 (TXA2) levels, as well as hepatic malondialdehyde (MDA) formation, but effectively elevated the serum nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and prostaglandin I2 (PGI2) levels, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), T-superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in high choline-fed mice. Hematoxylin-eosin (H&E) and oil red O staining also suggested that TSGP could exert the significant protection against endothelial dysfunction and liver injury in high choline-treated mice. These findings suggest that TSGP is of the saponins-enriched extract, and is a good candidate of dietary supplement and therapeutic application in vascular and hepatic oxidative injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Colina/farmacologia , Gynostemma , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , LDL-Colesterol/sangue , Endotélio Vascular/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Metilaminas , Camundongos , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tromboxano A2/sangue , Triglicerídeos/sangue
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