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1.
Carbohydr Polym ; 332: 121883, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431404

RESUMO

Silvetia siliquosa, the only species of the family Fucaceae in China, is used as a medicine food homology. Fucoidan from S. siliquosa was extracted by hot water twice thoroughly (13 % of total yield), and a purified fucoidan SSF with a molecular weight of 93 kD was obtained. Chemical composition analysis demonstrated that SSF was primarily composed of sulfate (21.68 wt%) and fucose (84 % of all neutral monosaccharides). IR, methylation analysis, NMR and ESI-MS results indicated SSF had the backbone of mainly (1 â†’ 3)-α-L-fucopyranose and minor (1 â†’ 4)-α-L-fucopyranose, with little 1,3 and 1,4 branched ß-D-Xylp and ß-D-Galp. The in vitro immunomodulatory test on RAW 264.7 cells showed that SSF could up-regulate the expression of immune related factors and proteins in a concentration-dependent manner, but the immunomodulatory effect disappeared from desulfated SSF. This research indicated that highly sulfated fucan possessed immunomodulatory effect and the importance of sulfate groups in the activity of SSF.


Assuntos
Polissacarídeos , Animais , Camundongos , Células RAW 264.7 , Polissacarídeos/farmacologia , Polissacarídeos/química , Sulfatos/química , Parede Celular
2.
Molecules ; 29(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474647

RESUMO

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 µM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1ß as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.


Assuntos
Aesculus , Camundongos , Animais , Aesculus/química , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa , Sementes/química , Lipopolissacarídeos/farmacologia , Óxido Nítrico/análise
3.
Carbohydr Polym ; 333: 121922, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494202

RESUMO

A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 105 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.


Assuntos
Receptor 4 Toll-Like , Vitaceae , Animais , Camundongos , Vitaceae/química , Polissacarídeos/química , Macrófagos , Células RAW 264.7
4.
Int J Med Mushrooms ; 26(3): 27-40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505901

RESUMO

In our previous study, we have established Russula pseudocyanoxantha as a unique species, playing a crucial role in indigenous diets through ages. The research also brought attention to bioactive potential of polysaccharide fraction extracted from the unexplored food using hot water. However, residue of the conventional process still contains therapeutic biopolymers that could further be utilized for pharmacological purposes instead of being discarded. Therefore, the current study aims to valorize the solid remnants, contributing to a deeper understanding of the novel taxon. Subsequently, the leftover was treated with cold alkali, leading to the preparation of a high-yield fraction (RP-CAP). Chemical characterization through FT-IR, GC-MS, HPTLC, and spectroscopy demonstrated presence of several monomers in the carbohydrate backbone, predominantly composed of ß-glucan. Furthermore, GPC chromatogram indicated presence of a homogeneous polymer with molecular weight of ~ 129.28 kDa. Subsequently, potent antioxidant activity was noted in terms of radical scavenging (O2·-, OH·, DPPH· and ABTS·+), chelating ability, reducing power and total antioxidant activity where EC50 values ranged from 472-3600 µg/mL. Strong immune-boosting effect was also evident, as the biopolymers stimulated murine macrophage cell proliferation, phagocytic activity, pseudopod formation, and NO as well as ROS synthesis particularly at the concentration of 100 µg/mL. In-depth analysis through RT-PCR revealed that the fraction stimulated synthesis of several inflammatory mediators, elucidating the mode of action through TLR/ NF-κB pathway. Therefore, the findings collectively suggest that RP-CAP possesses great potential to serve as a healthimproving component in functional food and pharmaceutical sectors.


Assuntos
Agaricales , Basidiomycota , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/química , Agaricales/química , NF-kappa B/metabolismo , Álcalis , Espectroscopia de Infravermelho com Transformada de Fourier , Basidiomycota/metabolismo , Células RAW 264.7 , Polissacarídeos/farmacologia , Polissacarídeos/química , Imunidade , Biopolímeros
5.
Drug Dev Res ; 85(2): e22173, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38515272

RESUMO

New pyridazine and pyridazinone derivatives 3a-g, 4a-f, 6a, and 6b were designed and synthesized. Cell viability of all compounds was established based on the viability of lipopolysaccharide-induced RAW264.7 macrophage cells determined via the MTT assay. In vitro inhibition assays on human COX-1 and COX-2 enzymes were conducted to probe the newly synthesized compounds' anti-inflammatory activity. The half maximal inhibitory concentration values for the most active compounds, 3d, 3e, and 4e towards COX-2 were 0.425, 0.519, and 0.356 µM, respectively, in comparison with celecoxib. The newly synthesized compounds' ability to inhibit the production of certain proinflammatory cytokines, such as inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-6, and prostaglandin-E2, was also estimated in lipopolysaccharide-induced macrophages (RAW264.7 cells). Compounds 3d and 3e were identified as the most potent cytokine production inhibitors. The results of molecular modeling studies suggested that these compounds were characterized by a reasonable binding affinity toward the active site of COX-2, when compared to a reference ligand. These results might be taken into consideration in further investigations into new anti-inflammatory agents.


Assuntos
Lipopolissacarídeos , Piridazinas , Camundongos , Animais , Humanos , Lipopolissacarídeos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Células RAW 264.7 , Piridazinas/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo
6.
PLoS One ; 19(2): e0297512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306362

RESUMO

The immune-enhancing activity of the combination of Platycodon grandiflorum and Salvia plebeian extracts (PGSP) was evaluated through macrophage activation using RAW264.7 cells. PGSP (250-1000 µg/mL) showed a higher release of NO in a dose-dependent manner. The results showed that PGSP could significantly stimulate the production of PGE2, COX-2, TNF-α, IL-1ß, and IL-6 in RAW264.7 cells and promote iNOS, COX-2, TNF-α, IL-1ß, IL-4, and IL-6 mRNA expression. Western blot analysis demonstrated that the protein expression of iNOS and COX-2 and the phosphorylation of ERK, JNK, p38, and NF-κB p65 were greatly increased in PGSP-treated cells. PGSP also promoted the phagocytic activity of RAW264.7 cells. All these results indicated that PGSP might activate macrophages through MAPK and NF-κB signaling pathways. Taken together, PGSP may be considered to have immune-enhancing activity and might be used as a potential immune-enhancing agent.


Assuntos
Platycodon , Salvia , Animais , Camundongos , NF-kappa B/metabolismo , Platycodon/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Salvia/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Interleucina-6/genética , Citocinas/genética , Citocinas/metabolismo , Células RAW 264.7 , Lipopolissacarídeos
7.
Zhongguo Zhong Yao Za Zhi ; 49(1): 130-140, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403346

RESUMO

This study induced biological stress in Sorbus pohuashanensis suspension cell(SPSC) with yeast extract(YE) as a bio-tic elicitor and isolated and identified secondary metabolites of triterpenoids produced under stress conditions. Twenty-six triterpenoids, including fifteen ursane-type triterpenoids(1-15), two 18,19-seco-ursane-type triterpenoids(16-17), four lupine-type triterpenoids(18-21), two cycloartane-type triterpenoids(22-23), and three squalene-type triterpenoids(24-26), were isolated and purified from the methanol extract of SPSC by chromatography on silica gel, MCI, Sephadex LH-20, and MPLC. Their structures were elucidated by spectroscopic analyses. All triterpenoids were isolated from SPSC for the first time and 22-O-acetyltripterygic acid A(1) was identified as a new compound. Selected compounds were evaluated for antifungal, antitumor, and anti-inflammatory activities, and compound 1 showed an inhibitory effect on NO production in LPS-induced RAW264.7 cells.


Assuntos
Triterpenos Pentacíclicos , Sorbus , Triterpenos , Animais , Camundongos , Sorbus/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Células RAW 264.7 , Estrutura Molecular
8.
Mar Drugs ; 22(2)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38393034

RESUMO

Six benzophenone derivatives, carneusones A-F (1-6), along with seven known compounds (7-13) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 µM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 µM.


Assuntos
Anti-Inflamatórios , Aspergillus , Animais , Camundongos , Estrutura Molecular , Aspergillus/química , Anti-Inflamatórios/farmacologia , Células RAW 264.7
9.
Anal Chim Acta ; 1296: 342333, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401928

RESUMO

Nitric oxide (NO) plays an essential role in regulating various physiological and pathological processes. This has spurred various efforts to develop feasible methods for the detection of NO. Herein we designed and synthesized a novel donor-acceptor fluorescent probe Car-NO for the selective and specific detection of NO. Reaction of Car-NO with NO generated a new donor-acceptor structure with strong intramolecular charge transfer (ICT) effect, and led to remarkable chromogenic change from yellow to blue and dramatic fluorescence quenching. Car-NO exhibited high selectivity, excellent sensitivity, and rapid response for the detection of NO. In addition, the nanoparticles prepared from Car-NO (i.e., Car-NO NPs) showed strong NIR emission and high selectivity/sensitivity. Car-NO NPs was successfully employed to image both endogenous and exogenous NO in HeLa and RAW 264.7 cells. The present findings reveal that Car-NO is a promising probe for the detection and bioimaging of NO.


Assuntos
Corantes Fluorescentes , Óxido Nítrico , Camundongos , Animais , Humanos , Corantes Fluorescentes/toxicidade , Corantes Fluorescentes/química , Células HeLa , Fluorescência , Células RAW 264.7
10.
Int J Med Mushrooms ; 26(1): 1-15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305258

RESUMO

Mushrooms are prevalently important sources of pharmaceutically active metabolites. Various mushroom species belonging to the Lentinus genus are recognized for their nutritional and therapeutic properties. One such species is L. sajor-caju, which is renowned in Southeast Asian nations for its culinary value. The primary goal of this study is to investigate the potential medicinal properties of L. sajor-caju, specifically its antioxidant, antibacterial, and anti-inflammatory effects. A hydroethanolic extract was formulated using dried basidiocarps, which exhibited a high phenolic content of approximately 14% and a flavonoid content of approximately 2.7%. The extract demonstrated significant antioxidant potential in in vitro reactions. The extract is sufficiently capable of scavenging free radicals (DPPH and ABTS) and chelate Fe2+ with EC50 values spanning from 186 to 390 µg/mL. In addition, considerable antimicrobial activity against tested pathogenic microorganisms was observed, as indicated by low MIC50 values (256-358 µg/mL). Moreover, the fraction was found to prevent heat-induced protein denaturation which signifies its anti-inflammatory potential. When tested on the RAW 264.7 cell line, reduction in the nitrite production, and downregulation of COX-2 and iNOS mRNA expression was observed which are the key regulator of inflammatory signalling systems. The study, therefore, recommends the use of L. sajor-caju in the medical and pharmaceutical industries for the benefit of humanity.


Assuntos
Agaricales , Basidiomycota , Lentinula , Agaricales/química , Antibacterianos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Ciclo-Oxigenase 2/genética , Etanol , Animais , Camundongos , Células RAW 264.7
11.
Int J Mol Sci ; 25(4)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38396824

RESUMO

Sasanquasaponin (SQS), a secondary metabolite that is derived from Camellia seeds, reportedly possesses notable biological properties. However, the anti-inflammatory effects of SQS and its underlying mechanisms remain poorly explored. Herein, we aimed to investigate the anti-inflammatory properties of SQS against lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells, focusing on the nuclear factor-κB (NF-κB) and MAPK signaling pathways. SQS was isolated using a deep eutectic solvent and D101 macroporous adsorption resin and analyzed using high-performance liquid chromatography. The viability of LPS-stimulated RAW264.7 was assessed using the CCK-8 assay. The presence of reactive oxygen species (ROS) was evaluated using 2',7'-dichlorofluorescein-diacetate. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected using reverse transcription-quantitative PCR and ELISA. Western blot was performed to analyze the protein expression of LPS-induced RAW264.7 cells. Herein, SQS exhibited anti-inflammatory activity: 30 µg/mL of SQS significantly reduced ROS generation, inhibited the LPS-induced expression of iNOS and COX-2, and attenuated the production of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. The anti-inflammatory activity was potentially mediated by inhibiting the phosphorylation of IκBα and p65 in the NF-κB signaling pathway and the phosphorylation of ERK and JNK in the MAPK signaling pathway. Accordingly, SQS could inhibit inflammation in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPK signaling pathways. This study demonstrated the potential application of SQS as an anti-inflammatory agent.


Assuntos
NF-kappa B , Saponinas , Fator de Necrose Tumoral alfa , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Interleucina-6/farmacologia , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo
12.
ACS Biomater Sci Eng ; 10(3): 1418-1434, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38319825

RESUMO

Protein adsorption after biomaterial implantation is the first stage of the foreign body response (FBR). However, the source(s) of the adsorbed proteins that lead to damaged associated molecular patterns (DAMPs) and induce inflammation have not been fully elucidated. This study examined the effects of different protein sources, cell-derived (from a NIH/3T3 fibroblast cell lysate) and serum-derived (from fetal bovine serum), which were compared to implant-derived proteins (after a 30 min subcutaneous implantation in mice) on activation of RAW 264.7 cells cultured in minimal (serum-free) medium. Both cell-derived and serum-derived protein sources when preadsorbed to either tissue culture polystyrene or medical-grade silicone induced RAW 264.7 cell activation. The combination led to an even higher expression of pro-inflammatory cytokine genes and proteins. Implant-derived proteins on silicone explants induced a rapid inflammatory response that then subsided more quickly and to a greater extent than the studies with in vitro cell-derived or serum-derived protein sources. Proteomic analysis of the implant-derived proteins identified proteins that included cell-derived and serum-derived, but also other proteinaceous sources (e.g., extracellular matrix), suggesting that the latter or nonproteinaceous sources may help to temper the inflammatory response in vivo. These findings indicate that both serum-derived and cell-derived proteins adsorbed to implants can act as DAMPs to drive inflammation in the FBR, but other protein sources may play an important role in controlling inflammation.


Assuntos
Reação a Corpo Estranho , Proteômica , Camundongos , Animais , Células RAW 264.7 , Macrófagos , Inflamação , Proteínas , Silicones
13.
Mol Med ; 30(1): 30, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395749

RESUMO

BACKGROUND: Sepsis is a systemic inflammatory response which is frequently associated with acute lung injury (ALI). Activating transcription factor 3 (ATF3) promotes M2 polarization, however, the biological effects of ATF3 on macrophage polarization in sepsis remain undefined. METHODS: LPS-stimulated macrophages and a mouse model of cecal ligation and puncture (CLP)-induced sepsis were generated as in vitro and in vivo models, respectively. qRT-PCR and western blot were used to detect the expression of ATF3, ILF3, NEAT1 and other markers. The phenotypes of macrophages were monitored by flow cytometry, and cytokine secretion was measured by ELISA assay. The association between ILF3 and NEAT1 was validated by RIP and RNA pull-down assays. RNA stability assay was employed to assess NEAT1 stability. Bioinformatic analysis, luciferase reporter and ChIP assays were used to study the interaction between ATF3 and ILF3 promoter. Histological changes of lung tissues were assessed by H&E and IHC analysis. Apoptosis in lungs was monitored by TUNEL assay. RESULTS: ATF3 was downregulated, but ILF3 and NEAT1 were upregulated in PBMCs of septic patients, as well as in LPS-stimulated RAW264.7 cells. Overexpression of ATF3 or silencing of ILF3 promoted M2 polarization of RAW264.7 cells via regulating NEAT1. Mechanistically, ILF3 was required for the stabilization of NEAT1 through direct interaction, and ATF3 was a transcriptional repressor of ILF3. ATF3 facilitated M2 polarization in LPS-stimulated macrophages and CLP-induced septic lung injury via ILF3/NEAT1 axis. CONCLUSION: ATF3 triggers M2 macrophage polarization to protect against the inflammatory injury of sepsis through ILF3/NEAT1 axis.


Assuntos
Fator 3 Ativador da Transcrição , Macrófagos , RNA Longo não Codificante , Sepse , Animais , Humanos , Camundongos , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Proteínas do Fator Nuclear 90/genética , Proteínas do Fator Nuclear 90/metabolismo , Células RAW 264.7 , Sepse/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
14.
Environ Geochem Health ; 46(2): 61, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38281271

RESUMO

The objective of this study was to investigate the effects of anthracene (Ant) with 3 rings, benzo[a]anthracene (BaA) with 4 rings and benzo[b]fluoranthene (BbF) with 5 rings in fine particulate matter (PM2.5) at different exposure times (4 h and 24 h) and low exposure levels (0 pg/mL, 0.1 pg/mL, 1 pg/mL, 100 pg/mL and 10,000 pg/mL) on RAW264.7 cells. The changes of interleukin-6 (IL-6) and oxidative stress levels in RAW264.7 cells were investigated by methyl-thiazolyl-tetrazolium (MTT) and enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to analyze the correlation between variables. Ant, BaA and BbF induced the secretion of IL-6 and the occurrence of oxidative stress in RAW264.7 cells. The inflammatory effect and oxidative damage were exacerbated with prolonged exposure time, increasing exposure concentration and increasing number of PAH rings. At the same time, IL-6 was found to have a certain correlation with the levels of ROS, MDA and SOD. Exposure to atmospheric PAHs at low concentrations can also produce toxic effects on cells, IL-6 and oxidative stress work together in cell damage. The study is expected to provide a theoretical and experimental basis for air pollution control and human health promotion.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/toxicidade , Antracenos/toxicidade , Interleucina-6 , Macrófagos/química , Estresse Oxidativo , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Animais , Camundongos , Células RAW 264.7
15.
Arch Biochem Biophys ; 753: 109916, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296016

RESUMO

During persistent hyperglycaemia, albumin, one of the major blood proteins, can undergo fast glycation. It can be expected that timely inhibition of protein glycation might be add quality years to diabetic patients' life. Therefore, this study was designed to analyse the role of silibinin to reduced or delay amadori adduct formation at early glycation and its beneficial effect to improve the glycated albumin structure and conformation. We also analysed cytotoxic effect of amadori-albumin in the presence of silibinin on murine macrophage cell line RAW cells by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. Formation of early glycated product (furosine) in all samples was confirmed by LCMS. Albumin incubated with glucose only showed presence of furosine like structure. Albumin treated with silibinin in the presence of glucose did not show such furosine like peak. This LCMS result showed the silibinin play a protective role in the formation of early glycated product. HMF contents were also reduced in the presence of silibinin, when albumin was incubated with increasing concentrations of silibinin (100 and 200 µM) in the presence of glucose. ANS binding fluorescence decrease by increasing silibinin concentrations with amadori-albumin. SDS-PAGE was also showed that no significant difference in the band mobility of albumin treated with silibinin as compared to native albumin. The secondary conformational alteration in amadori-albumin due to silibinin were confirmed by FTIR. This spectrum showed slight shift in amide I and Amide II band in albumin co-incubated with glucose and silibinin as compared to albumin incubated with glucose only. We further discussed about cytotoxic effect of amadori albumin and its prevention by silibinin. MTT assay results demonstrated that amadori-albumin showed cytotoxic effect on RAW cells but silibinin showed protective role and increased the cell viability. Moreover, the results showed that silibinin has anti-glycating potential and playing a role to prevent the formation of Amadori-albumin in-vitro. Silibinin possesses strong anti-glycating capacity and can improve albumin structure and function at early stage. It might be useful in delaying the progression of diabetes mellitus and its secondary complications at early stage.


Assuntos
Antineoplásicos , Diabetes Mellitus , Animais , Camundongos , Amidas , Glucose , Glicosilação , Reação de Maillard , Albumina Sérica/química , Albumina Sérica/metabolismo , Silibina/farmacologia , Células RAW 264.7
16.
J Ethnopharmacol ; 324: 117771, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38242218

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Melodinus axillaris W.T.Wang has been widely used as an important medicine in China. In the folk of China, its whole plant has been used for fractures, rheumatic heart disease, testitis, hernia, abdominal pain, and dyspepsia, etc. Despite its extensive use, there is a shortage of literature investigating the specific bioactive compounds and underlying mechanisms responsible for their anti-inflammatory effects. This knowledge gap serves as the primary impetus for conducting this study, which aims to shed light on the previously unexplored therapeutic potential of M. axillaris. AIM OF THE STUDY: This study aims to investigate the material basis and potential mechanism of anti-inflammatory activity of M. axillaris. MATERIALS AND METHODS: Compounds were isolated from the 95% ethanol extract of M. axillaris using a systematic phytochemical method. The structures were established by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD calculation, and DP4+ analysis. The anti-inflammatory activities of ethanol extract and compounds from M. axillaris were tested by an inflammation model of LPS-stimulated RAW264.7 cells in vitro. Western blot analysis was employed to evaluate the expressions of COX-2, iNOS, and NF-κB signaling pathways, aiming to elucidate the underlying mechanisms. RESULTS: Eleven undescribed monoterpenoid indole alkaloids (MIAs), axillines A-K (1-11), along with thirteen known analogs were isolated from M. axillaris. Compound 1 was the first representative of vincadine alkaloid with unprecedented 6/5/9/6/6 skeletons. Compounds 1-11 and ethanol extract showed significant anti-inflammatory effects in vitro. Among them, compound 2 had the best activity of inhibiting NO release (IC50 = 3.7 ± 0.9 µM). Additionally, subsequent Western blot analysis revealed that 2 could significantly inhibit the up-regulation of NF-κB signaling pathways, iNOS, and COX-2 in LPS-stimulated RAW264.7 cells, thereby demonstrating its anti-inflammatory activity. CONCLUSION: This study provides support for the traditional use of M. axillaris in terms of its anti-inflammatory properties and highlights the potential of MIAs as promising candidates for further development as anti-inflammatory drugs.


Assuntos
NF-kappa B , Alcaloides de Triptamina e Secologanina , Camundongos , Animais , NF-kappa B/metabolismo , Alcaloides de Triptamina e Secologanina/farmacologia , Ciclo-Oxigenase 2/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Extratos Vegetais/farmacologia , Etanol/farmacologia
17.
J Microbiol Biotechnol ; 34(2): 262-269, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38213284

RESUMO

Panax ginseng has been widely applied as an important herb in traditional medicine to treat numerous human disorders. However, the inflammatory regulation effect of P. ginseng distillate (GSD) has not yet been fully assessed. To determine whether GSD can ameliorate inflammatory processes, a GSD was prepared using the vacuum distillation process for the first time, and the regulation effect on lipopolysaccharide-induced macrophages was assessed. The results showed that GSD effectively inhibited nitric oxide (NO) formation and activation of inducible nitric oxide synthase (iNOS) mRNA in murine macrophage cell, but not cyclooxygenase-2 production. The mRNA expression pattern of tumor necrosis factor alpha and IL-6 were also reduced by GSD. Furthermore, we confirmed that GSD exerted its anti-inflammatory effects by downregulating c-Jun NH2-terminal kinase (JNK) phosphorylation, the extracellular signal-regulated kinase phosphorylation, and signaling pathway of nuclear factor kappa B (NF-κB). Our findings revealed that the inflammatory regulation activity of GSD could be induced by iNOS and NO formation inhibition mediated by regulation of nuclear factor kappa B and p38/JNK MAPK pathways.


Assuntos
Medicamentos de Ervas Chinesas , NF-kappa B , Panax , Extratos Vegetais , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Vácuo , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Panax/metabolismo , RNA Mensageiro , Óxido Nítrico/metabolismo
18.
Phytochemistry ; 220: 113997, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38244960

RESUMO

Aphanapolystachones A-C (1-3), three undescribed sesquiterpene-diterpene heterodimers, were obtained from the fruits of Aphanamixis polystachya. Their structures and absolute configurations were identified by extensive analysis of HR-ESI-MS, NMR, experimental and TD-DFT calculated ECD spectra. The biosynthetic pathway of them was also proposed, which is produced by key intermolecular Diels-Alder [4 + 2]-cycloaddition reaction between a guaiane sesquiterpene and an acyclic diterpene. Compounds 1-3 inhibited NO production in LPS activated RAW 264.7 cells with the IC50 values of 1.7 ± 0.2, 3.0 ± 0.3, 5.3 ± 0.3 µM, respectively, lower than that of the positive control L-NMMA (31.5 ± 2.6 µM). In addition, compounds 1-3 significantly reduced IL-6 secretion at diluted concentration of 0.4 µM.


Assuntos
Diterpenos , Meliaceae , Sesquiterpenos , Animais , Camundongos , Células RAW 264.7 , Frutas/química , Espectroscopia de Ressonância Magnética , Meliaceae/química , Diterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/análise , Estrutura Molecular
19.
Viruses ; 16(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257840

RESUMO

The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling pathways, RA's mechanism of action during coronavirus infection has not been thoroughly described. To determine RA's mechanism of action, we examined its effect against a mouse coronavirus, mouse hepatitis virus strain A59 (MHV). We demonstrated that RA significantly decreased viral titers in infected mouse L929 fibroblasts and RAW 264.7 macrophages. The reduced viral titers were associated with a corresponding decrease in MHV nucleocapsid protein expression. Using interferon regulatory factor 3 (IRF3) knockout RAW 264.7 cells, we demonstrated that RA-induced suppression of MHV required IRF3 activity. RNA-seq analysis of wildtype and IRF3 knockout RAW cells showed that RA upregulated calcium/calmodulin (CaM) signaling proteins, such as CaM kinase kinase 1 (CaMKK1). When treated with a CaMKK inhibitor, RA was unable to upregulate IRF activation during MHV infection. In conclusion, our results demonstrate that RA-induced protection against coronavirus infection depends on IRF3 and CaMKK.


Assuntos
Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Fator Regulador 3 de Interferon , Vírus da Hepatite Murina , Tretinoína , Replicação Viral , Animais , Camundongos , Aminoácidos , Antivirais/farmacologia , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Tretinoína/farmacologia , Replicação Viral/efeitos dos fármacos , Vírus da Hepatite Murina/efeitos dos fármacos , Vírus da Hepatite Murina/fisiologia , Células RAW 264.7 , Células L
20.
Phytochemistry ; 220: 114007, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38296177

RESUMO

Fourteen previously undescribed α-pyrone derivatives (1-14) together with four known analogs (15-18) were isolated from a traditional Chinese medicinal plant Hypericum henryi. Compounds (+)/(-)-1, 2, and 3 share a rare 6/6/4/6/6 polycyclic skeleton. Compound 14 was the first example of a 7,7-dimethyl-pyran-4-one moiety. Their structures were elucidated using comprehensive spectroscopic analyses and electronic circular dichroism calculations. The anti-inflammatory activities of 1-18 were screened in lipopolysaccharide-induced RAW264.7 cells. Among them, compounds 14, (+)-18, and (-)-18 exhibited inhibitory effects against nitric oxide production in LPS-induced RAW264.7 cells. Additionally, compound 14 suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-induced RAW264.7 cells. Furthermore, preliminary mechanism studies indicated that compound 14 suppressed the phosphorylation and degradation of the inhibitor of NF-κB, and this led to the inhibition of NF-κB activation.


Assuntos
Hypericum , NF-kappa B , Animais , Camundongos , NF-kappa B/metabolismo , Pironas/farmacologia , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Óxido Nítrico , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo
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