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1.
AAPS PharmSciTech ; 25(6): 151, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954171

RESUMO

The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.


Assuntos
Administração Intranasal , Epilepsia , Géis , Mucosa Nasal , Triterpenos , Animais , Administração Intranasal/métodos , Epilepsia/tratamento farmacológico , Géis/química , Mucosa Nasal/metabolismo , Mucosa Nasal/efeitos dos fármacos , Masculino , Triterpenos/administração & dosagem , Triterpenos/farmacocinética , Triterpenos/farmacologia , Triterpenos/química , Temperatura , Saponinas/administração & dosagem , Saponinas/química , Saponinas/farmacologia , Saponinas/farmacocinética , Química Farmacêutica/métodos , Disponibilidade Biológica , Ratos , Poloxâmero/química , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/farmacologia , Anticonvulsivantes/química
2.
PLoS One ; 19(7): e0305058, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38954702

RESUMO

OBJECTIVES: Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms. METHODS: Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing. RESULTS: AS-IV decreased the levels of TNF-α, IL-6, and IL-1ß in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria. CONCLUSION: AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.


Assuntos
Lesão Pulmonar Aguda , Microbioma Gastrointestinal , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Saponinas , Transdução de Sinais , Serina-Treonina Quinases TOR , Triterpenos , Animais , Saponinas/farmacologia , Saponinas/uso terapêutico , Triterpenos/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/microbiologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Masculino , Camundongos , Ratos Sprague-Dawley , Inflamação/tratamento farmacológico , Líquido da Lavagem Broncoalveolar/química , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 501-507, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38952089

RESUMO

Objective To investigate the effects of astragaloside IV(AS-IV) on the balance of T helper type 1 (Th1) and Th2 cells in mice with IgA nephropathy (IgAN) and its possible mechanism. Methods The IgAN model of BALB/c mice was established. Successfully modeled mice were randomly divided into four groups: model, AS-IV low dose, AS-IV medium dose and AS-IV high dose groups, with 10 mice in each group. Another 10 mice served as the control group. Mice in the low, medium and high dose groups were administered 12.5, 25 and 50 mg/kg AS-IV suspension (prepared in normal saline) by gavage, while the control and model groups were given an equivalent volume of normal saline. The 24-hour urinary protein (24 h UPr) content and urine red blood cell count were measured in each group. The levels of blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB) were determined. Serum interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-10 levels were detected by ELISA. The ratio of Th1/Th2 cells in peripheral blood of mice was detected using flow cytometry. Histopathological changes in the kidney of mice were observed by HE staining. RT-PCR and Western blot were used to detect the mRNA and protein expressions of T cell immunoglobulin and mucin domain gene 1 (TIM-1), Toll-like receptor 4 (TLR4) in mouse kidney tissue. Results Compared with the model group, in weeks 12 and 15, the urine red blood cell count, 24 h UPr, BUN, Scr, levels of IL-4 and IL-10, the proportion of Th2 cells, as well as the mRNA and protein expression levels of TIM-1 and TLR4 were significantly decreased in the low, medium and high dose groups of AS-IV, and the levels of ALB, IFN-γ, the proportion of Th1 cells and Th1/Th2 cell ratio were increased, with the high-dose group showing the best effects. Conclusion AS-IV can inhibit TIM-1 signaling pathway, increase the Th1/Th2 cell ratio, inhibit the inflammatory reaction, and alleviate the renal injury in IgAN mice.


Assuntos
Glomerulonefrite por IGA , Receptor Celular 1 do Vírus da Hepatite A , Camundongos Endogâmicos BALB C , Saponinas , Transdução de Sinais , Células Th1 , Células Th2 , Triterpenos , Animais , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/genética , Triterpenos/farmacologia , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/imunologia , Saponinas/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Camundongos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Interleucina-4/genética , Interleucina-4/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interferon gama/metabolismo , Interferon gama/genética , Masculino , Feminino
4.
PLoS One ; 19(7): e0306664, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968270

RESUMO

BACKGROUNDS: Malaria, a preventive and treatable disease, is still responsible for annual deaths reported in most tropical regions, principally in sub-Saharan Africa. Subunit recombinant transmission-blocking vaccines (TBVs) have been proposed as promising vaccines to succeed in malaria elimination and eradication. Here, a provisional study was designed to assess the immunogenicity and functional activity of alanyl aminopeptidase N (APN1) of Anopheles stephensi, as a TBV candidate, administered with MPL, CpG, and QS21 adjuvants in the murine model. METHODOLOGY/PRINCIPAL FINDINGS: The mouse groups were immunized with recombinant APN1 (rAPN1) alone or formulated with CpG, MPL, QS-21, or a combination of adjuvants (CMQ), and the elicited immune responses were evaluated after the third immunization. The standard membrane feeding assay (SMFA) measured the functional activity of antibodies against bacterial-expressed APN1 protein in adjuvanted vaccine groups on transmission of P. falciparum (NF54) to An. stephensi mosquitoes. Evaluation of mice vaccinated with rAPN1 formulated with distinct adjuvants manifested a significant increase in the high-avidity level of anti-APN1 IgG and IgG subclasses; however, rAPN1 induced the highest level of high-avidity anti-APN1 IgG1, IgG2a, and IgG2b antibodies in the immunized vaccine group 5 (APN1/CMQ). In addition, vaccine group 5 (receiving APN1/CMQ), had still the highest level of anti-APN1 IgG antibodies relative to other immunized groups after six months, on day 180. The SMFA data indicates a trend towards higher transmission-reducing activity in groups 2 and 5, which received the antigen formulated with CpG or a combination of three adjuvants. CONCLUSIONS/SIGNIFICANCE: The results have shown the capability of admixture to stimulate high-affinity and long-lasting antibodies against the target antigen to hinder Plasmodium parasite development in the mid-gut of An. stephensi. The attained results authenticated APN1/CMQ and APN1/CpG as a potent APN1-based TBV formulation which will be helpful in designing a vaccine in the future.


Assuntos
Adjuvantes Imunológicos , Anopheles , Antígenos CD13 , Vacinas Antimaláricas , Saponinas , Animais , Anopheles/parasitologia , Anopheles/imunologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Camundongos , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/administração & dosagem , Saponinas/farmacologia , Saponinas/administração & dosagem , Antígenos CD13/imunologia , Antígenos CD13/metabolismo , Feminino , Plasmodium falciparum/imunologia , Malária/prevenção & controle , Malária/transmissão , Malária/imunologia , Malária/parasitologia , Oligodesoxirribonucleotídeos/farmacologia , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/imunologia , Camundongos Endogâmicos BALB C , Malária Falciparum/prevenção & controle , Malária Falciparum/transmissão , Malária Falciparum/imunologia , Malária Falciparum/parasitologia
5.
Molecules ; 29(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999042

RESUMO

Steamed ginseng water (SGW) is a by-product of the repeated thermal processing of red ginseng, which is characterized by a high bioactive content, better skin care activity, and a large output. However, its value has been ignored, resulting in environmental pollution and resource waste. In this study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The antioxidant activity (DPPH, ABTS, FRAP, and OH) and chemical composition (total sugars, total saponins, and reducing and non-reducing sugars) were comprehensively evaluated based on the entropy weighting method. Four comparison groups (groups 1 and 3, groups 1 and 5, groups 1 and 7, and groups 1 and 9) were screened for 37 important common difference markers using OPLS-DA analysis. The entropy weight method was used to analyze the weights of the indicators; the seventh SGW sample was reported to have a significant weight. The results of this study suggest that heat treatment time and frequency can be an important indicator value for the quality control of SGW cycling operations, which have great potential in antioxidant products.


Assuntos
Antioxidantes , Panax , Espectrometria de Massas em Tandem , Panax/química , Antioxidantes/química , Antioxidantes/análise , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem/métodos , Temperatura Alta , Saponinas/química , Saponinas/análise , Extratos Vegetais/química
6.
Molecules ; 29(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38999186

RESUMO

Panax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants.


Assuntos
Metabolômica , Micorrizas , Panax notoginseng , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Triterpenos , Panax notoginseng/microbiologia , Panax notoginseng/química , Triterpenos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Micorrizas/metabolismo , Metabolômica/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Saponinas/metabolismo , Saponinas/química , Análise de Componente Principal , Metaboloma
7.
Molecules ; 29(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38999188

RESUMO

The leaves of Ilex paraguariensis (known as Yerba mate), used as a popular beverage, are a very well-recognized plant material with various biological activities, including analeptic (because of caffeine), anti-obesity (phenolics, saponins), antimicrobial, and antiviral (phenolics, saponins). Here, the chemical compositions of the leaves of two European Ilex species (× meserveae and aquifolium) with three varieties each were investigated. The terpenoid, saponin, and polyphenolic fractions were submitted for LC-MS or GC-MS analysis against a standard Mate leaf. In addition, the aroma profiles of all the species were analysed using HS-SPME-Arrow prior to GC-MS analysis. All fractions were subjected to antiviral and cytotoxic assays. We found 86 compounds in all accessions, with limonene, linalool, and p-cymene being predominant. There were minor similarities between the volatile compositions of the European and South American species. We found ursolic and oleanolic acid to be the main compounds in the terpenoid fraction. Mono-caffeoylquinic acids and di-caffeoylquinic acids were the main constituents of the polar fractions. About 180 compounds from the saponin group were tentatively identified, of which 9 and 3 were selected as distinctive markers for I. meserveae and I. aquifolium, respectively. Based on chemical screening, I. aquifolium Silver Queen was chosen as the source of terpenoid and saponin fractions and polyphenol extracts. The most substantial inhibition of cancer cell growth was observed with saponin in the case of the MCF7 (human breast cancer) cell line, while for LoVo and L929 cell lines (human colorectal cancer and reference mouse fibroblasts), it was slightly weaker. These results should be analysed further as a promising chemoprevention of colorectal and gastrointestinal cancers. Saponin and polyphenolic extracts exhibited similar activities against HSV-1 and HAdV-5, with 4-log reduction in virus titres. This study focuses our attention on a field of potential antiviral formulations derived from European holly.


Assuntos
Antivirais , Ilex , Extratos Vegetais , Folhas de Planta , Saponinas , Ilex/química , Antivirais/farmacologia , Antivirais/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Saponinas/farmacologia , Saponinas/química , Saponinas/análise , Animais , Polifenóis/farmacologia , Polifenóis/análise , Polifenóis/química , Terpenos/farmacologia , Terpenos/análise , Terpenos/química , Linhagem Celular Tumoral , Cromatografia Gasosa-Espectrometria de Massas , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/análise , Ilex paraguariensis/química
8.
Sci Rep ; 14(1): 15263, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961089

RESUMO

Ziziphi Spinosae Semen (ZSS) is the first choice for the treatment of insomnia. This research aimed to reveal the spatial distribution of identifying quality markers of ZSS and to illustrate the metabolite quality characteristics of this herbal medicine. Here, we performed a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in situ to detect and image 33 metabolites in ZSS, including three saponins, six flavonoids, four alkaloids, eight fatty acids, and 12 amino acids. The MALDI images of the metabolites clearly showed the heterogeneous spatial distribution in different regions of ZSS tissues, such as the cotyledon, endosperm, and radicle. The distribution area of two saponins, six flavonoids, and three alkaloids increased significantly after the fried processing of ZSS. Based on the ion images, samples with different processing technologies were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 23 major influencing components exerting higher ion intensities were identified as the potential quality markers of ZSS. Results obtained in the current research demonstrate that the processing of ZSS changes its content and distribution of the medicinal components. The analysis of MALDI-MSI provides a novel MS-based molecular imaging approach to investigate and monitor traditional medicinal plants.


Assuntos
Flavonoides , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ziziphus , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Ziziphus/química , Ziziphus/metabolismo , Flavonoides/análise , Flavonoides/metabolismo , Saponinas/análise , Saponinas/metabolismo , Alcaloides/análise , Alcaloides/metabolismo , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo
9.
J Nanobiotechnology ; 22(1): 393, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965602

RESUMO

BACKGROUND: The therapeutic strategies for acute ischemic stroke were faced with substantial constraints, emphasizing the necessity to safeguard neuronal cells during cerebral ischemia to reduce neurological impairments and enhance recovery outcomes. Despite its potential as a neuroprotective agent in stroke treatment, Chikusetsu saponin IVa encounters numerous challenges in clinical application. RESULT: Brain-targeted liposomes modified with THRre peptides showed substantial uptake by bEnd. 3 and PC-12 cells and demonstrated the ability to cross an in vitro blood-brain barrier model, subsequently accumulating in PC-12 cells. In vivo, they could significantly accumulate in rat brain. Treatment with C-IVa-LPs-THRre notably reduced the expression of proteins in the P2RX7/NLRP3/Caspase-1 pathway and inflammatory factors. This was evidenced by decreased cerebral infarct size and improved neurological function in MCAO rats. CONCLUSION: The findings indicate that C-IVa-LPs-THRre could serve as a promising strategy for targeting cerebral ischemia. This approach enhances drug concentration in the brain, mitigates pyroptosis, and improves the neuroinflammatory response associated with stroke.


Assuntos
Barreira Hematoencefálica , AVC Isquêmico , Lipossomos , Fármacos Neuroprotetores , Piroptose , Ratos Sprague-Dawley , Saponinas , Animais , Saponinas/farmacologia , Saponinas/química , Piroptose/efeitos dos fármacos , Ratos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Lipossomos/química , Masculino , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Células PC12 , Ácido Oleanólico/farmacologia , Ácido Oleanólico/química , Ácido Oleanólico/análogos & derivados , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo
10.
Sci Rep ; 14(1): 16434, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014061

RESUMO

Notoginseng saponin R1; ginsenosides Rg1, Re, Rb1, and Rd; the sum of the five saponins; and underground-part fresh weight (UPFW) of single plants were used as quality evaluation indices for Panax notoginseng (Burk.) F. H. Chen (P. notoginseng). Comprehensive evaluation of P. notoginseng samples from 30 production areas was performed using that MaxEnt model. Spatial pattern changes in suitable P. notoginseng habitats were predicted for current and future periods (2050s, 2070s, and 2090s) using SSP126 and SSP585 models. The results revealed that temperature, precipitation, and solar radiation were important environmental variables. Suitable habitats were located mainly in Yunnan, Guizhou, and Sichuan Provinces. The distribution core of P. notoginseng is predicted to shift southeast in the future. The saponin content decreased from the southeast to the northwest of Yunnan Province, which was contrary to the UPFW trend. This study provides the necessary information for the protection and sustainable utilization of P. notoginseng resources, and a theoretical reference for its application in the quality evaluation of Chinese medicinal products.


Assuntos
Mudança Climática , Ecossistema , Panax notoginseng , Panax notoginseng/crescimento & desenvolvimento , Panax notoginseng/química , China , Saponinas/análise , Ginsenosídeos/análise
11.
BMC Microbiol ; 24(1): 261, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39004720

RESUMO

BACKGROUND: The excessive application of chemical fertilizers in the cultivation of Astragalus mongholicus Bunge results in a reduction in the quality of the medicinal plant and compromises the sustainable productivity of the soil. PGPB inoculant is a hot topic in ecological agriculture research. In the cultivation of Astragalus mongholicus, the screened nitrogen-fixing bacteria can promote plant growth, however, whether it can promote the accumulation of main bioactive components remains unknown. In this study, mixed inoculants containing 5 strains of growth promoting bacteria (Rhizobium T16 , Sinorhizobium T21 , Bacillus J1 , Bacillus G4 and Arthrobacter J2) were used in the field experiment. The metabolic substances in the root tissues of Astragalus mongholicus were identified during the harvest period by non-targeted metabolomics method, and the differential metabolites between groups were identified by statistical analysis. Meanwhile, high-throughput sequencing was performed to analyze the changes of rhizosphere soil and endophytic microbial community structure after mixed microbial treatment. RESULTS: The results of non-targeted metabolism indicated a significant increase in the levels of 26 metabolites after treatment including 13 flavonoids, 3 saponins and 10 other components. The contents of three plant hormones (abscisic acid, salicylic acid and spermidine) also increased after treatment, which presumed to play an important role in regulating plant growth and metabolism. Studies on endosphere and rhizosphere bacterial communities showed that Rhzobiaceae, Micromonosporaceae, and Hypomicrobiaceae in endophytic, and Oxalobactereae in rhizosphere were significantly increased after treatment. These findings suggest their potential importance in plant growth promotion and secondary metabolism regulation. CONCLUSIONS: This finding provides a basis for developing nitrogen-fixing bacteria fertilizer and improving the ecological planting efficiency of Astragalus mongholicus.


Assuntos
Astrágalo , Microbiota , Raízes de Plantas , Rizosfera , Microbiologia do Solo , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Astrágalo/microbiologia , Astrágalo/metabolismo , Bactérias Fixadoras de Nitrogênio/metabolismo , Bactérias Fixadoras de Nitrogênio/genética , Saponinas/metabolismo , Bactérias/metabolismo , Bactérias/classificação , Bactérias/genética , Metabolômica , Arthrobacter/metabolismo , Arthrobacter/genética , Endófitos/metabolismo , Endófitos/genética , Rhizobium/metabolismo
12.
Immun Inflamm Dis ; 12(6): e1309, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38860765

RESUMO

BACKGROUND: Astragaloside IV (AS-IV) is the most active monomer in the traditional Chinese herbal medicine Radix Astragali, which has a wide range of antiviral, anti-inflammatory, and antifibrosis pharmacological effects, and shows protective effects in acute lung injury. METHODS: This study utilized the immunofluorescence, flow cytometry, enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, western blot, and hematoxylin and eosin staining methods to investigate the mechanism of AS-IV in reducing viral pneumonia caused by influenza A virus in A549 cells and BALB/c mice. RESULTS: The results showed that AS-IV suppressed reactive oxygen species production in influenza virus-infected A549 cells in a dose-dependent manner, and subsequently inhibited the activation of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 inflammasome and Caspase-1, decreased interleukin (IL) -1ß and IL-18 secretion. In BALB/c mice infected with Poly (I:C), oral administration of AS-IV can significantly reduce Poly (I:C)-induced acute pneumonia and lung pathological injury. CONCLUSIONS: AS-IV alleviates the inflammatory response induced by influenza virus in vitro and lung flammation and structural damage caused by poly (I:C) in vivo.


Assuntos
Caspase 1 , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR , Infecções por Orthomyxoviridae , Espécies Reativas de Oxigênio , Saponinas , Transdução de Sinais , Triterpenos , Animais , Saponinas/farmacologia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Camundongos , Transdução de Sinais/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Caspase 1/metabolismo , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamação/tratamento farmacológico , Vírus da Influenza A/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
14.
Molecules ; 29(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930835

RESUMO

Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material-solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC50 values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1ß in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.


Assuntos
Sequestradores de Radicais Livres , Panax , Extratos Vegetais , Raízes de Plantas , Saponinas , Panax/química , Saponinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Raízes de Plantas/química , Animais , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Antioxidantes/farmacologia , Antioxidantes/química
15.
Nutrients ; 16(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38931199

RESUMO

Saikosaponin D (SSD), derived from Bupleurum falcatum L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.


Assuntos
Apoptose , Autofagia , Neoplasias Colorretais , Neoplasias Pulmonares , Ácido Oleanólico , Saponinas , Saponinas/farmacologia , Ácido Oleanólico/farmacologia , Ácido Oleanólico/análogos & derivados , Autofagia/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Antineoplásicos Fitogênicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos dos fármacos , Camundongos Nus
16.
BMC Cancer ; 24(1): 682, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835015

RESUMO

BACKGROUND: Astragaloside IV (AS-IV) is one of the basic components of Astragali radix, that has been shown to have preventive effects against various diseases, including cancers. This study aimed to explore the role of AS-IV in hepatocellular carcinoma (HCC) and its underlying mechanism. METHODS: The cell viability, glucose consumption, lactate production, and extracellular acidification rate (ECAR) in SNU-182 and Huh7 cell lines were detected by specific commercial kits. Western blot was performed to analyze the succinylation level in SNU-182 and Huh7 cell lines. The interaction between lysine acetyltransferase (KAT) 2 A and phosphoglycerate mutase 1 (PGAM1) was evaluated by co-immunoprecipitation and immunofluorescence assays. The role of KAT2A in vivo was explored using a xenografted tumor model. RESULTS: The results indicated that AS-IV treatment downregulated the protein levels of succinylation and KAT2A in SNU-182 and Huh7 cell lines. The cell viability, glucose consumption, lactate production, ECAR, and succinylation levels were decreased in AS-IV-treated SNU-182 and Huh7 cell lines, and the results were reversed after KAT2A overexpression. KAT2A interacted with PGAM1 to promote the succinylation of PGAM1 at K161 site. KAT2A overexpression promoted the viability and glycolysis of SNU-182 and Huh7 cell lines, which were partly blocked following PGAM1 inhibition. In tumor-bearing mice, AS-IV suppressed tumor growth though inhibiting KAT2A-mediated succinylation of PGAM1. CONCLUSION: AS-IV inhibited cell viability and glycolysis in HCC by regulating KAT2A-mediated succinylation of PGAM1, suggesting that AS-IV might be a potential and suitable therapeutic agent for treating HCC.


Assuntos
Carcinoma Hepatocelular , Sobrevivência Celular , Glicólise , Neoplasias Hepáticas , Fosfoglicerato Mutase , Saponinas , Triterpenos , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Animais , Fosfoglicerato Mutase/metabolismo , Camundongos , Glicólise/efeitos dos fármacos , Triterpenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Saponinas/farmacologia , Linhagem Celular Tumoral , Histona Acetiltransferases/metabolismo , Camundongos Nus , Proliferação de Células/efeitos dos fármacos
17.
Front Immunol ; 15: 1412022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881898

RESUMO

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by local abnormal dilation of the aorta accompanied by vascular smooth muscle cell (VSMC) dysfunction and chronic inflammation. VSMC dedifferentiation, transdifferentiation, and increased expression of matrix metalloproteinases (MMPs) are essential causes of AAA formation. Previous studies from us and others have shown that Anemoside B4 (AB4), a saponin from Pulsatilla chinensis, has anti-inflammatory, anti-tumor, and regulatory effects on VSMC dedifferentiation. The current study aimed to investigate whether AB4 inhibits AAA development and its underlying mechanisms. By using an Ang II induced AAA model in vivo and cholesterol loading mediated VSMC to macrophage transdifferentiation model in vitro, our study demonstrated that AB4 could attenuate AAA pathogenesis, prevent VSMC dedifferentiation and transdifferentiation to macrophage-like cells, decrease vascular inflammation, and suppress MMP expression and activity. Furthermore, KLF4 overexpression attenuated the effects of AB4 on VSMC to macrophage-like cell transition and VSMC inflammation in vitro. In conclusion, AB4 protects against AAA formation in mice by inhibiting KLF4 mediated VSMC transdifferentiation and inflammation. Our study provides the first proof of concept of using AB4 for AAA management.


Assuntos
Aneurisma da Aorta Abdominal , Transdiferenciação Celular , Inflamação , Fator 4 Semelhante a Kruppel , Miócitos de Músculo Liso , Saponinas , Animais , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/prevenção & controle , Aneurisma da Aorta Abdominal/induzido quimicamente , Transdiferenciação Celular/efeitos dos fármacos , Fator 4 Semelhante a Kruppel/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Inflamação/metabolismo , Saponinas/farmacologia , Modelos Animais de Doenças , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Angiotensina II/farmacologia , Humanos
18.
Sci Rep ; 14(1): 13258, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858422

RESUMO

Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer accounting for approximately 85% of lung cancer cases. α-Hederin is a monodesmosidic triterpenoid saponin isolated from the leaves of Hedera helix L. or Nigella sativa and has been extensively studied for its antitumor activity against a variety of tumor cells. It has been suggested that α-Hederin is a potential regulator of autophagy and has high promise for application. However, the specific mechanism and characteristics of α-Hederin in regulating autophagy are not well understood. In this study, we confirmed the potential of α-Hederin application in lung cancer treatment and comprehensively explored the mechanism and characteristics of α-Hederin in regulating autophagy in lung cancer cells. Our results suggest that α-Hederin is an incomplete autophagy inducer that targets mTOR to activate the classical autophagic pathway, inhibits lysosomal acidification without significantly affecting the processes of autophagosome transport, lysosome biogenesis, autophagosome and lysosome fusion, and finally leads to impaired autophagic flux and triggers autophagic damage in NSCLC.


Assuntos
Autofagia , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Lisossomos , Ácido Oleanólico , Saponinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia , Saponinas/farmacologia , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Autofagossomos/metabolismo , Autofagossomos/efeitos dos fármacos , Células A549
19.
Sci Rep ; 14(1): 12988, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844823

RESUMO

Salinity stress significantly hinders plant growth by disrupting osmotic balance and inhibiting nutrient uptake, leading to reduced biomass and stunted development. Using saponin (SAP) and boron (B) can effectively overcome this issue. Boron decreases salinity stress by stabilizing cell walls and membranes, regulating ion balance, activating antioxidant enzymes, and enhancing water uptake. SAP are bioactive compounds that have the potential to alleviate salinity stress by improving nutrient uptake, modulating plant hormone levels, promoting root growth, and stimulating antioxidant activity. That's why the current study was planned to use a combination of SAP and boron as amendments to mitigate salinity stress in sweet potatoes. Four levels of SAP (0%, 0.1%, 0.15%, and 0.20%) and B (control, 5, 10, and 20 mg/L B) were applied in 4 replications following a completely randomized design. Results illustrated that 0.15% SAP with 20 mg/L B caused significant enhancement in sweet potato vine length (13.12%), vine weight (12.86%), root weight (8.31%), over control under salinity stress. A significant improvement in sweet potato chlorophyll a (9.84%), chlorophyll b (20.20%), total chlorophyll (13.94%), photosynthetic rate (17.69%), transpiration rate (16.03%), and stomatal conductance (17.59%) contrast to control under salinity stress prove the effectiveness of 0.15% SAP + 20 mg/L B treatment. In conclusion, 0.15% SAP + 20 mg/L B is recommended to mitigate salinity stress in sweet potatoes.


Assuntos
Boro , Ipomoea batatas , Estresse Salino , Saponinas , Ipomoea batatas/crescimento & desenvolvimento , Boro/farmacologia , Saponinas/farmacologia , Estresse Salino/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Clorofila/metabolismo , Sinergismo Farmacológico , Salinidade
20.
Sci Rep ; 14(1): 12917, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839811

RESUMO

Allii Macrostemonis Bulbus (AMB) is a traditional Chinese medicine with medicinal and food homology. AMB has various biological activities, including anti-coagulation, lipid-lowering, anti-tumor, and antioxidant effects. Saponins from Allium macrostemonis Bulbus (SAMB), the predominant beneficial compounds, also exhibited lipid-lowering and anti-inflammatory properties. However, the effect of SAMB on atherosclerosis and the underlying mechanisms are still unclear. This study aimed to elucidate the pharmacological impact of SAMB on atherosclerosis. In apolipoprotein E deficiency (ApoE-/-) mice with high-fat diet feeding, oral SAMB administration significantly attenuated inflammation and atherosclerosis plaque formation. The in vitro experiments demonstrated that SAMB effectively suppressed oxidized-LDL-induced foam cell formation by down-regulating CD36 expression, thereby inhibiting lipid endocytosis in bone marrow-derived macrophages. Additionally, SAMB effectively blocked LPS-induced inflammatory response in bone marrow-derived macrophages potentially through modulating the NF-κB/NLRP3 pathway. In conclusion, SAMB exhibits a potential anti-atherosclerotic effect by inhibiting macrophage foam cell formation and inflammation. These findings provide novel insights into potential preventive and therapeutic strategies for the clinical management of atherosclerosis.


Assuntos
Aterosclerose , Células Espumosas , Inflamação , Saponinas , Animais , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Saponinas/farmacologia , Camundongos , Inflamação/tratamento farmacológico , Inflamação/patologia , Allium/química , Masculino , Apolipoproteínas E/deficiência , Dieta Hiperlipídica/efeitos adversos , NF-kappa B/metabolismo , Camundongos Endogâmicos C57BL , Lipoproteínas LDL/metabolismo
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