Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.981
Filtrar
1.
Phytochemistry ; 176: 112392, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32512361

RESUMO

Multiple sclerosis (MS) in a multifactorial autoimmune disease in which reliable biomarkers are needed for therapeutic monitoring and diagnosis. Autoantibodies (autoAbs) are known biomarker candidates although their detection in biological fluids requires a thorough characterization of their associated antigens. Over the past twenty years, a reverse chemical-based approach aiming to screen putative autoantigens has underlined the role of glycans, in particular glucose, in MS. Despite the progress achieved, a lack of consensus regarding the nature of innate antigens as well as difficulties proposing new synthetic glucose-based structures have proved to be obstacles. Here is proposed a strategy to extend the current methodology to the field of natural glycosides, in order to dramatically increase the diversity of glycans that could be tested. Triterpene saponins from the Sapindaceace family represent an optimal starting material as their abundant description in the literature has revealed a prevalence of glucose-based oligosaccharides. Blighia welwitschii (Sapindaceae) was thus selected as a case study and twelve triterpene saponins were isolated and characterized. Their structures were elucidated on the basis of 1D and 2D NMR as well as mass spectrometry, revealing seven undescribed compounds. A selection of natural glycosides exhibiting various oligosaccharide moieties were then tested as antigens in enzyme-linked immunosorbent assay (ELISA) to recognize IgM antibodies (Abs) in MS patients' sera. Immunoassay results indicated a correlation between the glycan structures and their antibody recognition capacity, allowing the determination of structure-activity relationships that were coherent with previous studies. This approach might help to identify sugar epitopes putatively involved in MS pathogenesis, which remains poorly understood.


Assuntos
Blighia , Esclerose Múltipla , Saponinas , Triterpenos , Glicosídeos , Humanos
2.
Braz J Med Biol Res ; 53(7): e9628, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520209

RESUMO

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-ß1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inflamação/prevenção & controle , Ophiopogon/química , Estresse Oxidativo/efeitos dos fármacos , Saponinas/uso terapêutico , Espirostanos/uso terapêutico , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina
3.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1648-1656, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489045

RESUMO

To enrich the transcriptome data in rhizome of Polygonatum cyrtonema seedlings, identify candidate functional genes involved in steroidal saponin biosynthesis and provide genetic resources for the research on anabolism pathway and regulatory mechanism of active components in P. cyrtonema, Illumina platform was applied to perform transcriptomic sequencing of rhizome of P. cyrtonema, followed by a series of bioinformatics analysis on RNA-seq data, including de novo assembly, annotation, classification and metabolic pathway analysis of the assembled unigene. Meanwhile, a deep analysis on the steroidal saponin biosynthesis in secondary metabolism pathway was performed. The results showed a total of 126 546 unigene were obtained by de novo transcriptome assembly, of which 47 226 were annotated. Of these, 16 499 unigene were mapped to 132 specific pathways, of which 2 768 were identified to be involved in 22 secondary metabolic pathways. One hundred and thirteen unigene were identified from the transcriptome database, which encoded 27 metabolic enzymes associated with steroidal saponin biosynthesis and shared similarity with 45 functional genes in Arabidopsis thaliana. In conclusion, a series of candidate functional genes, which might be involved in steroidal saponin biosynthesis, were selected from the transcriptome database of P. cyrtonema rhizome. Further investigation of these candidate genes will provide insight into their actual functions in the steroidal saponin biosynthetic pathway in P. cyrtonema. In addition, this study also provide abunant reference data for transcriptome characterization of P. cyrtonema and has important significance for functional genomics of P. cyrtonema.


Assuntos
Polygonatum , Vias Biossintéticas , Perfilação da Expressão Gênica , Rizoma , Saponinas , Transcriptoma
4.
Phytochemistry ; 176: 112404, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447090

RESUMO

Silene species are known for their use in traditional medicine in treating several diseases. To the authors' knowledge there is no report on the chemical composition of S. odontopetala. Therefore, the phytochemical investigation of the methanol extract of S. odontopetala was carried out, leading to the isolation of six undescribed oleanane-type glycosides along with the known saponin azukisaponin IV. Their structures were elucidated by the analysis of 1D and 2D-NMR experiments, along with mass spectrometry analysis. The cytotoxic activity of oleanane-type saponins was evaluated against a small panel of cancer cell lines, including PC-3 (prostate carcinoma cells), MCF-7 (breast cancer cells), A549 (alveolar basal carcinoma cells), and HeLa (cervical carcinoma cells). Furthermore, the activity of isolated compounds against a normal cell line HEK-293, used for assessing their cytotoxicity, was evaluated.


Assuntos
Antineoplásicos Fitogênicos , Saponinas , Silene , Triterpenos , Linhagem Celular Tumoral , Glicosídeos , Células HEK293 , Humanos , Estrutura Molecular
5.
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
6.
Phytochemistry ; 175: 112363, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32278135

RESUMO

Three undescribed seco-ursane stereoisomers, ilexcornutosides A-C, two undescribed triterpenoid saponins, ilexcornutosides D-E, and 11 known triterpenoids were isolated from the leaves of Ilex cornuta Lindl. & Paxton. Ilexcornutosides A-C and F with the same planar structures are unique 13(18)-ene-18,19-seco-ursane skeleton triterpenoids, identified as (3S,12R)-3-O-[ß-d-glucopyranosyl-(1 â†’ 2)-α-l-arabinopyranosyl]-12-hydroxyl-19-oxo-18,19-secours-13(18)-en-28,21-lactone. Among them, ilexcornutosides A and F (or ilexcornutosides B and C) are a pair of diastereomers at the C-20 position; ilexcornutosides A and C (or ilexcornutosides B and F) are a pair of diastereomers with epimerization at the C-21. Their structures were established by extensive spectroscopic (IR, 1D and 2D NMR, and HR-ESI-MS) and chemical analyses. The absolute configurations of ilexcornutosides A, B, D and F were determined by a single crystal X-ray diffraction analysis with a Cu Kα radiation. The inhibitory effect of ilexcornutosides A-F on the PPARγ expression was assessed in the 3T3-L1-Lenti-PPARγ-Luc cells using a single luciferase reporter assay. Ilexcornutosides A and C showed a comparable activity in decrease of the PPARγ expression to the positive control (T0070907) at 5 µM.


Assuntos
Ilex , Saponinas , Triterpenos , Estrutura Molecular , Folhas de Planta , Estereoisomerismo
7.
Phytochemistry ; 175: 112367, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32339958

RESUMO

Phytochemical investigation of the ethanolic extract of Glandularia x hybrida roots resulted in the isolation and identification of five previously undescribed saponins, 3-O-ß-ᴅ-xylopyranosyl-hederagenin-28-O-ß-ᴅ-glucopyranosyl (1→2)-O-ß-ᴅ-glucopyranosyl ester, 3-O-ß-ᴅ-xylopyranosyl-hederagenin-28-O-ß-ᴅ-glucopyranosyl (1→2)-[ß-ᴅ-glucopyranosyl (1→6)]-ß-ᴅ-glucopyranosyl ester, hederagenin-28-O-ß-ᴅ-glucopyranosyl (1→2)-[ß-ᴅ-glucopyranosyl (1→6)]-ß-ᴅ-glucopyranosyl ester, 23-O-acetyl-3-O-ß-ᴅ-xylopyranosyl-pomolic acid-28-O-ß-ᴅ-glucopyranosyl ester, and 23-O-acetyl-pomolic acid-3-O-ß-ᴅ-xylopyranoside, along with eleven structurally diverse compounds. The structural characterizations of the isolated compounds were determined using physical data, comprehensive 1D and 2D NMR spectral analysis, and HRESIMS. All isolated saponins are hederagenin or pomolic acid glycosides conjugated with differentiable sugar units bound to C-3 and/or C-28 of the aglycone through ether and/or ester glycosidic linkages, respectively. Structural diversity of these isolated secondary metabolites would have a great impact on the future chemosystematic studies of this plant. Four saponins, obtained in good yield were evaluated for their anti-inflammatory activities in a rat model using the carrageenan-induced paw edema protocol. Two of these exhibited significant anti-inflammatory activities demonstrated through inhibition of the paw edema by 64 and 60%.


Assuntos
Saponinas , Triterpenos , Verbenaceae , Animais , Glicosídeos , Espectroscopia de Ressonância Magnética , Raízes de Plantas , Ratos
8.
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
9.
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
10.
Am J Physiol Cell Physiol ; 318(6): C1226-C1237, 2020 06 01.
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
11.
Zhongguo Zhong Yao Za Zhi ; 45(1): 157-162, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237425

RESUMO

This paper was aimed to observe the effect of anemoside B4(hereinafter referred to as B4) on cisplatin-induced acute kidney injury in mice, and to investigate its possible mechanism in renal protection from inflammation and apoptosis aspects. Mice were divided into normal group, model group, dexamethasone positive group and B4 high, middle and low dose groups(5, 2.5, and 1.25 mg·kg~(-1 )doses). All the other mice groups except normal group were given with tail vein injection of cisplatin(15 mg·kg~(-1)) to induce acute kidney injury models. The drug administration was started on the day of modeling, and lasted for 4 days. After 1 hour of the last injection, orbital blood was collected. After the serum was separated, serum urea nitrogen(BUN), creatinine(Cre), total protein(TP), and albumin(ALB) were tested by using an automatic biochemical analyzer; the changes of kidney pathological morphology were observed by PAS staining; the protein expression levels of inflammatory factors including nucleotide binding oligomerization domain-like receptor(NLRP3), cysteinyl aspartate specific proteinase 1(caspase-1), interleukin-18(IL-18), interleukin-1ß(IL-1ß), tumor necrosis factor(TNF-α), and interleukin-6(IL-6) and apoptosis factors including p53, caspase-3, cleaved-caspase-3, Bcl-2 associated X protein(Bax), and B-cell lymphoma-2(Bcl-2) were analyzed by Western blot. The results showed that B4 significantly reduced the serum BUN and Cre contents, and alleviated pathological changes in renal tissues, such as the shedding and degeneration of renal tubular epithelial cells, tubulin tubule type. B4 significantly down-regulated the protein expressions of p53, Bax, cleaved-caspase-3 in the kidney and up-regulated the expression of Bcl-2/Bax. In model group, however, no significant up-regulation was observed in the protein expression levels of inflammatory cytokines(NLRP3, pro-caspase-1, IL-18, IL-1ß, TNF-α, IL-6). The results suggested that B4 had a certain protective effect on cisplatin-induced acute kidney injury, and could activate p53 signaling pathway related apoptotic factors. B4 renal protective effect was mainly related to the regulation of p53 signaling pathway, while NLRP3 inflammasome and related inflammatory factors had no obvious response in this model.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Apoptose , Inflamação , Saponinas/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Animais , Proteínas Reguladoras de Apoptose , Citocinas , Rim , Camundongos
12.
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
13.
Food Chem ; 321: 126706, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32234636

RESUMO

The purpose of this study was to fabricate ternary complexes composed of pea protein isolate (PPI), high methoxyl pectin (HMP) and individual surfactants including rhamnolipid (Rha), tea saponin (TS) and Ethyl lauroyl arginate (LAE), for the delivery of resveratrol (Res). A combination of electrostatic attraction and hydrophobic interaction was dominantly responsible for the formation of HMP-surfactant-PPI complexes. The physicochemical properties of the ternary complexes were affected by surfactant types as well as mass ratios of individual surfactant to PPI. HMP-Rha-PPI1:1, HMP-TS-PPI1:1 and HMP-LAE-PPI1:25 complexes had higher denaturation temperatures of 82.78 ± 0.31, 80.21 ± 0.02 and 79.98 ± 0.86 ℃, respectively. The HMP-Rha-PPI1:1 ternary complex could be an effective delivery system, which were effective to retard photo- and thermal- degradation of Res as well as delayed the release of Res in in vitro digestion.


Assuntos
Glicolipídeos/química , Proteínas de Ervilha/química , Pectinas/química , Resveratrol/química , Tensoativos/química , Interações Hidrofóbicas e Hidrofílicas , Saponinas/química
14.
Zhongguo Zhong Yao Za Zhi ; 45(3): 513-517, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237507

RESUMO

Cerebral ischemia is also known as ischemic stroke. In recent years, research on neuroprotection after ischemia has became a hot spot as stroke can result in symptoms of nerve damages such as hemiplegia, learning and memory disorders. The key factors that cause the death of cells include excitotoxicity, oxidative damage, nitrosative stress and inflammation. However, there is no effective preparation for the treatment of post-ischemic nerve defects at present, so it is urgent to find and develop effective drugs for the treatment of nerve damages after ischemia. Traditional Chinese medicine has advantages and potentials in the treatment of neurological diseases. Many scholars have carried out related researches on the active ingredients of traditional Chinese medicine and achieved some good results. In this context, the researches on the neuroprotective effects of traditional Chinese medicines such as tetramethylpyrazine, butylphthalide and total saponins of Panax notoginseng were reviewed. The author found that the neuroprotective researches of traditional Chinese medicine mostly focused on anti-apoptosis, anti-inflammatory and anti-oxidative stress, but those effects were not sounique to the nervous system. Furthermore, most ingredients of traditional Chinese medicine showed a poor water-soluble property. In view of the research status and existing problems of traditional Chinese medicine in nerve injury, the suggestions for the research and development of the potent neuroprotective agents were proposed in this study from the perspective of pharmacological mechanism research and preparation theory.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Infarto Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Benzofuranos/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Panax notoginseng , Pirazinas/uso terapêutico , Saponinas/uso terapêutico
15.
Zhongguo Zhong Yao Za Zhi ; 45(3): 617-622, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237521

RESUMO

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.


Assuntos
Artéria Renal/patologia , Traumatismo por Reperfusão/tratamento farmacológico , Saponinas/uso terapêutico , Transdução de Sinais , Animais , Rim , Ligadura , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Receptor 4 Toll-Like/metabolismo
16.
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
17.
Planta Med ; 86(8): 565-570, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32325509

RESUMO

Bacopa monnieri is an Ayurvedic plant with rising interest in the pharmacological effects of its extract and constituents, including flavonoids, saponins, and triterpenes such as cucurbitacins, betulinic acid, and bacosine. The latter two compounds are isomeric 3-hydroxy lupenoic acids, which vary only in the arrangement of the carboxylic acid group and the methyl group at C-27 and C-28 and the orientation of the hydroxy group at C-3. In this study, we have reinvestigated the contents of betulinic acid and bacosine, respectively, in extracts from various commercially available B. monnieri powders and food supplements. To our surprise, HPLC-ion trap time-of-flight analyses identified only betulinic acid, but not bacosine, in all extracts under study, which was verified by GC-MS, HPLC-ELSD, 1D NMR (1H,13C), and 2D NMR (1H,1H COSY, 1H,13C HMBC, 1H,13C HSQC, 1H,1H NOESY) experiments. Moreover, it turned out that commercially available reference samples of bacosine were structurally identical with betulinic acid.


Assuntos
Bacopa , Saponinas , Triterpenos , Cromatografia Líquida de Alta Pressão , Extratos Vegetais
18.
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
19.
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
20.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA