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1.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445384

RESUMO

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague-Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fígado Gorduroso/prevenção & controle , Inulina/administração & dosagem , Saponinas/administração & dosagem , Tribulus/química , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/análise , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Inulina/farmacologia , Fígado/química , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia , Estreptozocina , Resultado do Tratamento
2.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3672-3677, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402291

RESUMO

To explore the effect of ophiopogonin D on main fatty acid metabolic enzymes in human cardiomyocyte AC-16,so as to provide reference for cardiovascular protection mechanism and safe clinical application of Ophiopogon japonicus.CCK-8 (cell counting kit-8) was used to detect the effect of different concentrations of ophiopogonin D on the viability of cardiomyocytes.Meanwhile,the effect of different concentrations of ophiopogonin D on the morphology and quantity of cardiomyocytes was observed under microscope.The effect of ophiopogonin D on the mRNA expression of CYP2J2,CYP4F3,CYP4A11,CYP4A22 and CYP4F2 in cardiomyocytes was detected by RT-PCR.Western blot was used to detect the protein expression of CYP4F3 in different concentrations of ophiopogonin D.Compared with the control group,low-concentration ophiopogonin D had no effect on the viability of cardiomyocytes.However,ophiopogonin D with a concentration of higher than 20µmol·L~(-1)could promote the viability.Under the microscope,ophiopogonin D with a concentration of below 100µmol·L~(-1)had no significant effect on the morphology and number of cardiomyocytes.RT-PCR results showed that compared with the control group,5µmol·L~(-1)ophiopogonin D could slightly up-regulate mRNA expressions of CYP2J2 and CYP4F3,while high-concentration ophiopogonin D (10 and 20µmol·L~(-1)) could significantly induce mRNA expressions of CYP2J2and CYP4F3 in a dose-dependent manner (P<0.05).The same concentration of ophiopogonin D had a little effect on the mRNA expressions of CYP4A11,CYP4A22 and CYP4F2.Western blot results showed that 20µmol·L~(-1)ophiopogonin D could significantly induce the protein expression of CYP4F3 in a dose-dependent manner (P<0.05).Based on the above results,ophiopogonin D (less than100µmol·L~(-1)) has no effect on the viability of AC-16 cardiomyocytes.Ophiopogonin D (less than 100µmol·L~(-1)) can selectively induce the expressions of CYP2J2 and CYP4F3,regulate the metabolic pathway of fatty acid signaling molecules,and thus protecting the cardiovascular system.


Assuntos
Saponinas , Espirostanos , Ácidos Graxos , Humanos , Miócitos Cardíacos , Saponinas/farmacologia , Espirostanos/farmacologia
3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 397-401, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374260

RESUMO

Objective: To study the protective effects and mechanisms of total saponins of Codonopsis (TSC) on ulcerative colitis in rats. Methods: Fifty male Wistar rats were randomly divided into 5 groups: control group, model group, salazosulfadiazine (SASP) positive control group (0.3 g/kg), TSC high- and low-dose experimental groups(1.2, 0.4 g/kg). UC rat model was established by trinitrobenzene sulfonic acid (TNBS)/ ethanol enema. After administration for 21 days, the rats' symptoms and signs, disease activity index (DAI), colonic mucosal injury index (CMDI) and colonic tissue morphology were observed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α) in colon tissues were determined. Protein expression of nuclear nuclear transcription factor-κB (NF-κB) in colon tissues was detected. Finally, the effect of TCS therapy was evaluated. Results: Compared with the control group, the DAI and CMDI scores of the rats in the model group were increased significantly, meanwhile the colonic mucosa was seriously damaged, indicating that the model was successful. Compared with the model group, the TSC high and low dose groups could significantly reduce the DAI and CMDI score (P<0.05) and improve the colonic mucosa form. TSC also could increase the SOD activity and decrease MDA content in colon tissues(P<0.05), while inhibit the levels of IL-6 and TNF-α mRNA in the colon tissues and promote the expression of IL-10 mRNA (P<0.01). At the same time, TSC reduced the expressions of NF-κB protein in the colon (P<0.01). The TSC high-dose group was superior to the low-dose group (P<0.05). Conclusion: TSC has significant protective effects on ulcerative colonic mucosal damage in UC rats, and there is a dose-dependent relationship; its mechanism may be related to anti-lipid peroxidation and inhibiting the NF-κB signaling pathway to regulate the release of inflammatory factors.


Assuntos
Codonopsis , Colite Ulcerativa , Saponinas , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Masculino , NF-kappa B , Ratos , Ratos Wistar , Saponinas/farmacologia , Ácido Trinitrobenzenossulfônico
4.
Biomed Pharmacother ; 139: 111665, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243607

RESUMO

Multicomponent herbal formulas (MCHFs) have earned a wide reputation for their definite efficacy in preventing or treating chronic complex diseases. However, holistic elucidation of the causal relationship between the bioavailable ingredients of MCHFs and their multitarget interactions is very challenging. To solve this problem, pharmacokinetics/pharmacometabolomics-pharmacodynamics (PK/PM-PD) combined with a multivariate biological correlation-network strategy was developed and applied to a classic MCHF, Baoyuan decoction (BYD), to clarify its active components and synergistic mechanism against cardiac hypertrophy (CH). First, multiple plasma metabolic biomarkers for ß-adrenergic agonist-induced CH rats were identified by using untargeted metabolomic profiling, and then, these CH-associated endogenous metabolites and the absorbed BYD-compounds in plasma at different treatment stages after oral administration of BYD were analyzed by using targeted PK and PM. Second, the dynamic relationship of BYD-related compounds and CH-associated endogenous metabolites and signaling pathways was built by using multivariate and bioinformatic correlation analysis. Finally, metabolic-related PD indicators were predicted and further verified by biological tests. The results demonstrated that the bioavailable BYD-compounds, such as saponins and flavonoids, presented differentiated and distinctive metabolic features and showed positive or negative correlations with various CH-altered metabolites and PD-indicators related to gut microbiota metabolism, amino acid metabolism, lipid metabolism, energy homeostasis, and oxidative stress at different treatment stages. This study provides a novel strategy for investigating the dynamic interaction between BYD and the biosystem, providing unique insight for disclosing the active components and synergistic mechanisms of BYD against CH, which also supplies a reference for other MCHF related research.


Assuntos
Cardiomegalia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacologia , Extratos Vegetais/farmacocinética , Aminoácidos/metabolismo , Animais , Biomarcadores/metabolismo , Cardiomegalia/metabolismo , Sinergismo Farmacológico , Flavonoides/farmacocinética , Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Saponinas/farmacocinética , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos
5.
Phytochemistry ; 190: 112870, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34271297

RESUMO

Six undescribed oleanane-type saponins, named as Hylomeconosides L-Q, were isolated from the whole herb of Hylomecon Japonica, their structures were determined by analysis of 1D and 2D-NMR (1H-1H COSY, HSQC, and HMBC) spectroscopic data, mass spectrometry (HRESI-MS) and chromatographic data (GC and LC). Their structures were identified as 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-galactopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-L-arabinopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-glucuronopyranosyl gypsogenin 28-O-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-rhamnopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-quinovopyranoside; 3-O-ß-D-galactopyranosyl-(1 â†’ 2)-[α-L-rhamnopyranosyl-(1 â†’ 3)]-ß-D-glucuronopyranosyl quillaic acid 28-O-ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 4)-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-galactopyranoside. Hylomeconosides L-Q showed selective cytotoxicities against human cancer cell lines A549, AGS, HeLa, Huh 7, HT29 and K562. These results represent a contribution to the chemotaxonomy of the saponins of Hylomecon Japonica and their bioactivities.


Assuntos
Saponinas , Triterpenos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Triterpenos/farmacologia
6.
Plant Physiol Biochem ; 166: 857-873, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34237604

RESUMO

Urochloa ruziziensis, a cover plant used in no-till systems, can suppress weeds in the field through their chemical compounds, but the mode of action of these compounds is still unknown. The present study aimed to investigate the effects of a saponin-rich butanolic extract from U. ruziziensis straw (BfUr) and one of its components, protodioscin on an eudicot Ipomoea grandifolia and a monocot Digitaria insularis weed. The anatomy and the morphology of the root systems and several parameters related to energy metabolism and antioxidant defense systems were examined. The IC50 values for the root growth inhibition by BfUr were 108 µg mL-1 in D. insularis and 230 µg mL-1 in I. grandifolia. The corresponding values for protodioscin were 34 µg mL-1 and 54 µg mL-1. I. grandifolia exhibited higher ROS-induced peroxidative damage in its roots compared with D. insularis. In the roots of both weeds, the BfUr and protodioscin induced a reduction in the meristematic and elongation zones with a precocious appearance of lateral roots, particularly in I. grandifolia. The roots also exhibited features of advanced cell differentiation in the vascular cylinder. These alterations were similar to stress-induced morphogenic responses (SIMRs), which are plant adaptive strategies to survive in the presence of toxicants. At concentrations above their IC50 values, the BfUr or protodioscin strongly inhibited the development of both weeds. Such findings demonstrated that U. ruziziensis mulches may contribute to the use of natural and renewable weed control tools.


Assuntos
Diosgenina , Saponinas , Diosgenina/análogos & derivados , Diosgenina/farmacologia , Plantas Daninhas , Poaceae , Saponinas/farmacologia
7.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202717

RESUMO

Timosaponin BII is one of the most abundant Anemarrhena saponins and is in a phase II clinical trial for the treatment of dementia. However, the pharmacological activity of timosaponin BII does not match its low bioavailability. In this study, we aimed to determine the effects of gut microbiota on timosaponin BII metabolism. We found that intestinal flora had a strong metabolic effect on timosaponin BII by HPLC-MS/MS. At the same time, seven potential metabolites (M1-M7) produced by rat intestinal flora were identified using HPLC/MS-Q-TOF. Among them, three structures identified are reported in gut microbiota for the first time. A comparison of rat liver homogenate and a rat liver microsome incubation system revealed that the metabolic behavior of timosaponin BII was unique to the gut microbiota system. Finally, a quantitative method for the three representative metabolites was established by HPLC-MS/MS, and the temporal relationship among the metabolites was initially clarified. In summary, it is suggested that the metabolic characteristics of gut microbiota may be an important indicator of the pharmacological activity of timosaponin BII, which can be applied to guide its application and clinical use in the future.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Saponinas/farmacocinética , Esteroides/farmacocinética , Animais , Biotransformação , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia , Esteroides/farmacologia
8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(8): 716-721, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34236031

RESUMO

Objective To explore the effects of Panax notoginseng saponins (PNS) on the proliferation, apoptosis, migration and invasion of osteosarcoma cell line U2OS and its possible molecular mechanism. Methods Human osteosarcoma cell line U2OS was cultured and treated with (0, 200, 400, 600, 800, 1000) µg/mL PNS. The proliferation of U2OS was detected by CCK-8 method. Annexin V-FITC/PI double labeling combined with flow cytometry was used to analyze cell apoptosis. Clone formation assay was used to detect the clone formation ability of the cells. TranswellTM invasion assay was performed to detect cell invasion. TranswellTM migration assay and wound-healing assay were used to determine cell migration. Western blotting was used to detect the expression of Notch1 and downstream protein Hes1 in U2OS cells. Results Compared with the control group, PNS could inhibit the proliferation of U2OS cells and the formation of clonal plaques, increase cell apoptosis rate, weaken the ability of migration and invasion and decrease the expression levels of Notch1 and Hes1 in the cells in a dose-dependent manner. Conclusion PNS can significantly inhibit the proliferation, migration and invasion and promote cell apoptosis of U2OS cells by blocking Notch1 signaling pathway.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Panax notoginseng , Saponinas , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Osteossarcoma/tratamento farmacológico , Receptor Notch1/genética , Saponinas/farmacologia
9.
Int J Biol Macromol ; 185: 31-39, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34144063

RESUMO

This study was aimed to determine the efficacy of combination of fucoidan from the brown algae Fucus evanescens (FeF) or its derivatives with thornasteroside A (ThA) or asteropsiside A (AsA) from the starfish Asteropsis carinifera in combating human melanoma cells. In vitro MTS and soft agar methods were performed to determine effect of FeF, its derivatives, ThA, AsA or their combination on proliferation and colony formation of SK-MEL-28 cells in 2D and 3D culture. Desulfation of FeF, but not deacetylation, led decreasing of its Mw and anti-proliferative activity. The combinatorial effect of FeF with ThA and AsA depended on the sequences of treatment by compounds. There was additive anticancer effect of FeF with ThA or AsA during simultaneous treatment of cells. ThA and AsA were not active against SK-MEL-28 cells after their pre-treatment with FeF. Potential synergism of action was identified only when SK-MEL-28 cells were pre-treated with ThA and AsA and then by FeF. This process going through the regulation of MEK1/2/ERK1/2/MSK1 pathway and expression of the cell cycle proteins as determined by Western Blot. Thus, the combination of fucoidan with the asterosaponins opens up the prospects for the development of effective combined chemotherapeutic methods for melanoma treatment.


Assuntos
Antineoplásicos/farmacologia , Fucus/química , Melanoma/metabolismo , Polissacarídeos/farmacologia , Saponinas/farmacologia , Estrelas-do-Mar/química , Animais , Antineoplásicos/química , Carbazóis/química , Carbazóis/farmacologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/tratamento farmacológico , Modelos Biológicos , Polissacarídeos/química , Saponinas/química
10.
Int J Biol Macromol ; 183: 2248-2261, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34111482

RESUMO

The recent emergence of the novel coronavirus (SARS-CoV-2) has resulted in a devastating pandemic with global concern. However, to date, there are no regimens to prevent and treat SARS-CoV-2 virus. There is an urgent need to identify novel leads with anti-viral properties that impede viral pathogenesis in the host system. Esculentoside A (EsA), a saponin isolated from the root of Phytolacca esculenta, is known to exhibit diverse pharmacological properties, especially anti-inflammatory activity. To our knowledge, SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) to enter host cells. This is mediated through the proteins of SARS-CoV-2, especially the spike glycoprotein receptor binding domain. Thus, our primary goal is to prevent virus replication and binding to the host, which allows us to explore the efficiency of EsA on key surface drug target proteins using the computational biology paradigm approach. Here, the anti-coronavirus activity of EsA in vitro and its potential mode of inhibitory action on the S-protein of SARS-CoV-2 were investigated. We found that EsA inhibited the HCoV-OC43 coronavirus during the attachment and penetration stage. Molecular docking results showed that EsA had a strong binding affinity with the spike glycoprotein from SARS-CoV-2. The results of the molecular dynamics simulation revealed that EsA had higher stable binding with the spike protein. These results demonstrated that Esculentoside A can act as a spike protein blocker to inhibit SARS-CoV-2. Considering the poor bioavailability and low toxicity of EsA, it is suitable as novel lead for the inhibitor against binding interactions of SARS-CoV-2 of S-protein and ACE2.


Assuntos
Enzima de Conversão de Angiotensina 2 , Antivirais , COVID-19/tratamento farmacológico , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ácido Oleanólico/análogos & derivados , SARS-CoV-2 , Saponinas , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/química , Antivirais/farmacologia , Linhagem Celular Tumoral , Coronavirus Humano OC43/química , Coronavirus Humano OC43/metabolismo , Humanos , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , SARS-CoV-2/química , SARS-CoV-2/fisiologia , Saponinas/química , Saponinas/farmacologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo
11.
Molecules ; 26(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068164

RESUMO

Astragaloside IV (AS-IV) is one of the major bio-active ingredients of huang qi which is the dried root of Astragalus membranaceus (a traditional Chinese medicinal plant). The pharmacological effects of AS-IV, including anti-oxidative, anti-cancer, and anti-diabetic effects have been actively studied, however, the effects of AS-IV on liver regeneration have not yet been fully described. Thus, the aim of this study was to explore the effects of AS-IV on regenerating liver after 70% partial hepatectomy (PHx) in rats. Differentially expressed mRNAs, proliferative marker and growth factors were analyzed. AS-IV (10 mg/kg) was administrated orally 2 h before surgery. We found 20 core genes showed effects of AS-IV, many of which were involved with functions related to DNA replication during cell division. AS-IV down-regulates MAPK signaling, PI3/Akt signaling, and cell cycle pathway. Hepatocyte growth factor (HGF) and cyclin D1 expression were also decreased by AS-IV administration. Transforming growth factor ß1 (TGFß1, growth regulation signal) was slightly increased. In short, AS-IV down-regulated proliferative signals and genes related to DNA replication. In conclusion, AS-IV showed anti-proliferative activity in regenerating liver tissue after 70% PHx.


Assuntos
Ciclo Celular , Replicação do DNA , Regulação para Baixo , Hepatectomia , Regeneração Hepática/efeitos dos fármacos , Fígado/citologia , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Replicação do DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Fator de Crescimento de Hepatócito/metabolismo , Fígado/efeitos dos fármacos , Fígado/cirurgia , Masculino , Anotação de Sequência Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Saponinas/química , Análise de Sequência de RNA , Fator de Crescimento Transformador beta1/metabolismo , Triterpenos/química
12.
Ecotoxicol Environ Saf ; 220: 112393, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34098426

RESUMO

Previous study found that pedunsaponin A (PA) influenced the cytoskeleton of Pomacea canaliculata hemocytes, leading to depolarization and haemocyte destruction and eventually to snail death. In this study, we analysed the changes in protein expression by iTRAQ-mediated proteomics and identified 51 downregulated proteins. Among these, we focused on proteins related to cytoskeletal function and identified neural Wiskott-Aldrich syndrome isoform X1 (PcnWAS). The full-length PcnWAS gene contains 9791 bp and includes an open reading frame of 1401 bp that encodes 735 amino acids with a predicted molecular mass of 49.83 kD. PcnWAS exhibited a relatively distant genetic relationship with known species; the closest homologue is Biomphalaria glabrata (57%). RNA interference (RNAi) was adopted to verify the function of PcnWAS after screening the siRNA sequence with an efficiency of 97%. Interference with the gene expression of PcnWAS did not lead to snail death, but the depolarization level increased, which demonstrated that PcnWAS is an important depolarization-related protein. The results of PA treatment of snails subjected to RNAi proved that interfering with PcnWAS gene expression decreased the molluscicidal activity of PA toward P. canaliculata; snail mortality after RNAi was significantly lower (40%) than that in PA-treated snails without RNAi (54%), while the survival rate and depolarization level in haemocytes were not significant, indicating that PcnWAS is only one of the important target proteins of PA in P. canaliculata. This study lays the foundation for further exploration of the molecular mechanism by which PA kills this harmful snail.


Assuntos
Citoesqueleto/efeitos dos fármacos , Gastrópodes/efeitos dos fármacos , Moluscocidas/farmacologia , Saponinas/farmacologia , Triterpenos/farmacologia , Proteína da Síndrome de Wiskott-Aldrich/metabolismo , Animais , Regulação para Baixo , Gastrópodes/genética , Gastrópodes/metabolismo , Hemócitos/efeitos dos fármacos , Proteômica , Interferência de RNA , Proteína da Síndrome de Wiskott-Aldrich/genética
13.
Chem Biodivers ; 18(7): e2100335, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34089236

RESUMO

Ardisia crenata Sims (Primulaceae) occurs in natural habitats in two varieties, bearing red or white fruits. While roots of the red-berried ardisia are valued as a medicinal product, the pharmacological activity of which is attributed to triterpene saponins, including ardisiacrispin A, data on the white-berried variety are scarce. A TLC-densitometric method was developed and validated to estimate the levels of saponins, calculated as ardisiacrispin A, in different plant parts in both varieties. Their content amounted to 22.17±4.75 and 25.72±1.46 mg/g d.w. in roots, and 2.64±0.74 and 3.43±0.70 mg/g d.w. in fruits of red-berried and white-berried ardisia, respectively. Assessment of cytotoxicity of ardisiacrispin A and A. crenata extracts on a panel of human cancer cell lines revealed a similar effect of root extracts from both varieties, with the highest potency against melanoma WM793 and colon cancer Caco2. Thus, roots of the white-berried variety may be treated as a substitute for red-berried ardisia and serve as an alternative source for the acquisition of plant material rich in bioactive saponins.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ardisia/química , Ácido Oleanólico/análogos & derivados , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Antineoplásicos Fitogênicos/análise , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ácido Oleanólico/análise , Ácido Oleanólico/farmacologia , Extratos Vegetais/análise , Raízes de Plantas/química , Saponinas/análise
14.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070938

RESUMO

The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis.


Assuntos
Hepatócitos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Ácido Palmítico/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Saponinas/farmacologia , Triterpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica , Glicerídeos/classificação , Glicerídeos/metabolismo , Glicerol-3-Fosfato O-Aciltransferase/antagonistas & inibidores , Glicerol-3-Fosfato O-Aciltransferase/genética , Glicerol-3-Fosfato O-Aciltransferase/metabolismo , Glicerofosfolipídeos/classificação , Glicerofosfolipídeos/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Metabolismo dos Lipídeos/genética , Lipidômica , Ácido Palmítico/toxicidade
15.
Free Radic Biol Med ; 171: 112-123, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33992678

RESUMO

Defective autophagy occurred in osteoblasts under stress induced by high glucose and played an essential role in the development of diabetic osteoporosis. Timosaponin BII, a steroidal saponin isolated from the rhizomes of Anemarrhena asphodeloides Bunge, possessed anti-osteoporosis properties. In this study, we investigated the efficacy and mechanism of timosaponin BII on diabetic osteoporosis. Timosaponin BII attenuated the deterioration in the microarchitecture of the tibias in diabetic rats. Furthermore, treatment with timosaponin BII dose-dependently reduced hyperglycemia-induced cell apoptosis in primary osteoblasts from rat calvaria. High glucose-exposed osteoblasts exhibited increased mitochondrial superoxide level, decreased mitochondrial membrane potential and impaired autophagic flux, which was attenuated by timosaponin BII, as evidenced by the upregulation of autophagosome numbers, LC3B puncta formation and Beclin1 expression. The antiapoptotic and antioxidative effect of timosaponin BII were repressed by the autophagy inhibitor 3-methyladenine and enhanced by the autophagy inducer rapamycin. Further studies showed that timosaponin BII suppressed the phosphorylation of mTOR and S6K, as well as the downstream factors NFκB and IκB, consequently activating autophagy and decreasing apoptosis. Of note, coincubation of timosaponin BII with MHY1485, a pharmacological activator of mTOR, diminished the protein expression of Bcl2 induced by timosaponin BII, which was in parallel with decreased autophagy and increased phosphorylation of NFκB and IκB. Overexpression of NFκB reduced timosaponin BII-evoked autophagy and promoted apoptosis. The in vivo results showed that oral administration of timosaponin BII downregulated the phosphorylation of mTOR and NFκB and upregulated Beclin1 expression in the proximal tibias of diabetic rats. These results suggested that timosaponin BII attenuated high glucose-induced oxidative stress and apoptosis through activating autophagy by inhibiting mTOR/NFκB signalling in osteoblasts.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Osteoporose , Saponinas , Animais , Apoptose , Autofagia , Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Osteoblastos , Osteoporose/tratamento farmacológico , Ratos , Saponinas/farmacologia , Transdução de Sinais , Esteroides/farmacologia , Serina-Treonina Quinases TOR/genética
16.
Chem Biol Interact ; 345: 109534, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34051206

RESUMO

Sepsis triggers liver dysfunction with high morbidity and mortality. Here, we elucidated the effect of anemoside B4 on sepsis in cecal ligation and puncture (CLP)-induced mouse model and LPS-induced primary hepatocytes. Following CLP surgery, septic mice were intraperitoneally injected with anemoside B4 (50 or 100 mg/kg). Anemoside B4 improved septic mouse survival rate, decreased serum AST and ALT levels and attenuated liver histopathologic damages. Western blot analysis showed that anemoside B4 elevated the expression of Beclin-1, LC3II/LC3I, Atg3, Atg5, and Atg7, and reduced p62, suggesting the restoration of autophagy flux in liver. More autophagic vesicles were observed in liver after anemoside B4 treatment using transmission electron microscopy. Using ELISA and commercial enzyme kits, we found that anemoside B4 decreased serum TNF-α, IL-6, and IL-1ß levels and increased CAT, SOD and GSH activities. TUNEL staining and western blot revealed that anemoside B4 suppressed cell apoptosis, along with decreased Bax, leaved caspase-3, cleaved PARP, but increased Bcl-2. Consistent with in vivo findings, anemoside B4 inhibited apoptosis, inflammatory response, and oxidative stress and enhanced autophagy in LPS-induced primary hepatocytes. Importantly, these cellular processes were possibly mediated by mTOR/p70S6K signaling, as reflected by the offset of 3-MA in the immunosuppression of anemoside B4.


Assuntos
Autofagia/efeitos dos fármacos , Fígado/lesões , Fígado/patologia , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Saponinas/farmacologia , Sepse/patologia , Serina-Treonina Quinases TOR/metabolismo , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Citoproteção/efeitos dos fármacos , Interleucina-1beta/sangue , Interleucina-6/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue
17.
Food Chem ; 358: 129903, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933971

RESUMO

Historically, asparagus is a vegetable with abundant phytochemicals (polyphenols, saponins, asparagusic acid, and alkaloids) and crucial bioactivities (neuroprotective, antianxiety, antityrosinase, antioxidant, antibacterial, and antiasthma effects). Numerous investigations indicated that processing technologies have a significant influence on the physicochemical, functional, and microstructural characteristics of asparagus. This review presents an updated overview of novel applications of processing technologies, including ultrasound treatments (in terms of extraction, purification, and preservation), heating treatments (hydrothermal treatments, thermal treatments, and combination heating treatments), high-pressure processing, representative shelf-life extension technologies, and green extraction technologies. These physical technologies enhance the yields of bioactive substances, bioactivities and product quality. In addition, utilizing the novel technologies (ohmic heating, cold plasma, pulsed electric fields, membrane processing) and conventional technologies with novel effects to fully develop the potential of asparagus should also be taken into consideration in the future.


Assuntos
Asparagus (Planta)/química , Armazenamento de Alimentos/métodos , Indústria de Processamento de Alimentos/métodos , Compostos Fitoquímicos/química , Alcaloides/química , Alcaloides/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Embalagem de Alimentos/instrumentação , Embalagem de Alimentos/métodos , Calefação , Compostos Fitoquímicos/farmacologia , Gases em Plasma , Polifenóis/química , Polifenóis/farmacologia , Saponinas/química , Saponinas/farmacologia , Ultrassom/métodos
18.
Braz J Med Biol Res ; 54(7): e10240, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34008751

RESUMO

Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.


Assuntos
Vírus da Dengue , Saponinas , Solanum , Antivirais/farmacologia , Saponinas/farmacologia , Replicação Viral , Vírus da Febre Amarela
19.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2260-2266, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047129

RESUMO

Non-alcoholic steatohepatitis(NASH) was induced by high-sugar and high-fat diet in mice to investigate the intervention effect of total saponins from Panax japonicus(TSPJ) and explore its possible mechanism. Mice were fed with high-sugar and high-fat diet to establish NASH model, and intervened with different doses of TSPJ(15, 45 mg·kg~(-1)). The animals were fed for 26 weeks. The histomorphology and pathological changes of liver tissues were observed by HE staining. The transcriptional expression levels of miR-199 a-5 p, autophagy related gene 5(ATG5) and inflammatory cytokines interleukin-6(IL-6), interleukin-1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in mouse liver were measured by quantitative Real-time polymerase chain reaction(qRT-PCR). Western blot was used to detect the expression of autophagy-related proteins ATG5, P62/SQSTM1(P62), and microtubule-associated protein light chain 3(LC3)-I/Ⅱ proteins in mouse liver. The expression of P62 protein was detected by immunofluorescence staining. In order to verify the targeting regulation relationship between miR-199 a-5 p and ATG5, miR mimic/inhibitor NC and miR-199 a-5 p mimic/inhibitor were transfected into Hepa 1-6 cells, and the expression of ATG5 mRNA and protein was detected. pMIR-reportor ATG5-3'UTR luciferase reporter gene plasmid was constructed and co-transfected with miR mimic/inhibitor NC and miR-199 a-5 p mimic/inhibitor into Hepa 1-6 cells to detect luciferase activity. In vivo, HE staining in the model group showed typical fatty degeneration and inflammatory infiltration, with increased expression of miR-199 a-5 p and decreased expression of ATG5 mRNA and protein. The expression of autophagy-associated protein P62 increased significantly, the ratio of LC3Ⅱ/Ⅰ decreased, and the transcriptional expression of inflammatory factors increased significantly. After the intervention by TSPJ, the pathological performance of liver tissue was significantly improved, the expression of miR-199 a-5 p decreased and the expression of ATG5 mRNA and protein increased, the expression of autophagy-associated protein P62 decreased significantly, the ratio of LC3Ⅱ/Ⅰ increased, and the transcriptional expression of inflammatory cytokines IL-6, IL-1ß and TNF-α decreased significantly. In vitro, it was found that the expression of ATG5 mRNA and protein and luciferase activity decreased significantly in miR-199 a-5 p overexpression cells, while after inhibition of miR-199 a-5 p expression, the expression level of ATG5 mRNA and protein and luciferase activity increased. The results showed that TSPJ can improve NASH in mice fed with high-sugar and high-fat diet, and its mechanism may be related to the regulation of miR-199 a-5 p/ATG5 signal pathway, the regulation of autophagy activity and the improvement of inflammatory response of NASH.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Panax , Saponinas , Animais , Autofagia , Proteína 5 Relacionada à Autofagia , Camundongos , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Saponinas/farmacologia
20.
Exp Mol Med ; 53(5): 956-972, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34035463

RESUMO

An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the two main SARS-CoV-2 infection routes via lysosome- and transmembrane protease serine 2 (TMPRSS2)-driven entry. Mechanistically, PD prevents host entry of SARS-CoV-2 by redistributing membrane cholesterol to prevent membrane fusion, which can be reinstated by treatment with a PD-encapsulating agent. Furthermore, the inhibitory effects of PD are recapitulated by the pharmacological inhibition or gene silencing of NPC1, which is mutated in patients with Niemann-Pick type C (NPC) displaying disrupted membrane cholesterol distribution. Finally, readily available local foods or herbal medicines containing PG root show similar inhibitory effects against SARS-CoV-2 infection. Our study proposes that PD is a potent natural product for preventing or treating COVID-19 and that briefly disrupting the distribution of membrane cholesterol is a potential novel therapeutic strategy for SARS-CoV-2 infection.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Saponinas/farmacologia , Serina Endopeptidases/metabolismo , Triterpenos/farmacologia , Internalização do Vírus/efeitos dos fármacos , Antivirais/química , COVID-19/metabolismo , Linhagem Celular , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Modelos Moleculares , Platycodon/química , SARS-CoV-2/fisiologia , Saponinas/química , Triterpenos/química
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