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1.
PLoS One ; 19(7): e0299965, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39018291

RESUMEN

The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 µM, 95% CI = 7.4 to 10.4 µM) was comparable to that of paracetamol (IC50 = 7.73 µM, 95% CI = 6.14 to 9.73 µM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.


Asunto(s)
Antiinflamatorios no Esteroideos , Citocinas , Diterpenos , Diterpenos/farmacología , Animales , Ratones , Humanos , Antiinflamatorios no Esteroideos/farmacología , Células RAW 264.7 , Citocinas/metabolismo , Óxido Nítrico/metabolismo , Antiinflamatorios/farmacología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , FN-kappa B/metabolismo , Dinoprostona/metabolismo , Lipopolisacáridos/farmacología , Células THP-1 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ibuprofeno/farmacología , Ibuprofeno/uso terapéutico , Interferón gamma/metabolismo , Selectina E/metabolismo
2.
J Clin Med ; 12(22)2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-38002684

RESUMEN

Endometriosis, a chronic condition affecting around 10-14% of women, is challenging to manage, due to its complex pathogenesis and limited treatment options. Research has suggested a potential role of the gut microbiota and the endocannabinoid system in the development and progression of endometriosis. This narrative review aims to explore the role of, and any potential interactions between, the endocannabinoid system (ECS) and the gut microbiota in endometriosis. This review found that both the ECS and microbiota influence endometriosis, with the former regulating inflammation and pain perception and the latter influencing immune responses and hormonal balance. There is evidence that a dysregulation of the endocannabinoid system and the gut microbiota influence endometriosis symptoms and progression via changes in CB1 receptor expression and increased circulating levels of endocannabinoids. Microbial imbalances in the gut, such as increases in Prevotella, have been directly correlated to increased bloating, a common endometriosis symptom, while increases in E. coli have supported the bacterial contamination hypothesis as a potential pathway for endometriosis pathogenesis. These microbial imbalances have been correlated with increases in inflammatory markers such as TNF-α and IL-6, both often raised in those with endometriosis. Protective effects of the ECS on the gut were observed by increases in endocannabinoids, including 2-AG, resulting in decreased inflammation and improved gut permeability. Given these findings, both the ECS and the gut microbiota may be targets for therapeutic interventions for endometriosis; however, clinical studies are required to determine effectiveness.

3.
Biomol Ther (Seoul) ; 31(1): 27-39, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36319441

RESUMEN

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokinesuppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-É£-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaol-curcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

4.
Front Pharmacol ; 13: 825842, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35991882

RESUMEN

Crocins (CRs) and the related active constituents derived from Crocus sativus L. (Saffron) have demonstrated protective effects against cerebral ischemia and ischemic stroke, with various bioactivities including neuroprotection, anti-neuroinflammation, antioxidant, and cardiovascular protection. Among CRs, crocin (CR) has been shown to act on multiple mechanisms and signaling pathways involved in ischemic stroke, including mitochondrial apoptosis, nuclear factor kappa light chain enhancer of B cells pathway, S100 calcium-binding protein B, interleukin-6 and vascular endothelial growth factor-A. CR is generally safe and well-tolerated. Pharmacokinetic studies indicate that CR has poor bioavailability and needs to convert to crocetin (CC) in order to cross the blood-brain barrier. Clinical studies have shown the efficacy of saffron and CR in treating various conditions, including metabolic syndrome, depression, Alzheimer's disease, and coronary artery disease. There is evidence supporting CR as a treatment for ischemic stroke, although further studies are needed to confirm their efficacy and safety in clinical settings.

5.
Front Pharmacol ; 13: 818166, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35662723

RESUMEN

Synergy plays a prominent role in herbal medicines to increase potency and widen the therapeutic windows. The mechanism of synergy in herbal medicines is often associated with multi-targeted behavior and complex signaling pathways which are challenging to elucidate. This study aims to investigate the synergistic mechanism of a combination (GT) of ginger (G) and turmeric (T) extracts by exploring the modulatory activity in lipopolysaccharides (LPS)-induced inflammatory pathways and key molecular targets. A Bioplex ProTM mouse cytokine 23-plex assay was utilized to assess the broad anti-cytokine activity of GT in LPS and interferon (IFN)-É£ (both at 50 ng/mL)-activated RAW 264.7 cells. The inhibitory effects of individual and combined G and T on major proinflammatory mediators including nitric oxide (NO), tumor necrosis factor (TNF) and interleukin (IL)-6 were tested using Griess reagents and ELISA assays, respectively. Immunofluorescent staining and Western blot were used to investigate the modulatory effect of GT on key proteins in the LPS/TLR4 signaling transduction. The regulation of murine microRNA miR-155-5p was tested using real-time PCR. The IC50 value and combination index (CI) values were used to demonstrate potency and synergistic interaction, respectively. GT synergistically attenuated a range of pro-inflammatory mediators including inducible NO, major cytokines (TNF and IL-6) and secondary inflammatory cytokines (GM-CSF and MCP-1). GT significantly inhibited LPS-induced NF-kB p65 translocation, the activation of TLR4, TRAF6, and phosphorylation of JNK and c-JUN. Moreover, the suppressive effect of GT on each of the protein targets in this axis was stronger than that of the individual components. Real-time PCR analysis showed that GT suppressed miR-155-5p to a greater extent than G or T alone in LPS-stimulated cells. Our study demonstrates the synergistic mechanism of GT in downregulating LPS-induced proinflammatory pathways at the miRNA and protein levels. Our results establish a scientific basis for the combined application of G and T as an advanced therapeutic candidate in inflammatory diseases with broad and synergistic anti-inflammatory activity and multi-targeted mechanisms.

6.
Molecules ; 27(12)2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35745000

RESUMEN

This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2−related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes.


Asunto(s)
Curcumina , Zingiber officinale , Animales , Antiinflamatorios/farmacología , Curcuma/metabolismo , Curcumina/farmacología , Zingiber officinale/metabolismo , Hemo-Oxigenasa 1 , Humanos , Interferón gamma , Lipopolisacáridos , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/farmacología
7.
Int J Mol Sci ; 22(18)2021 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-34576262

RESUMEN

Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN-38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN-38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II ß and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN-38 (CSN-38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN-38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of CBD and its synergistic combination with SN-38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer.


Asunto(s)
Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Cannabidiol/química , Proteómica/métodos , Adenocarcinoma/metabolismo , Antineoplásicos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis , Neoplasias de la Mama/metabolismo , Cannabidiol/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Dactinomicina/análogos & derivados , Dactinomicina/farmacología , Docetaxel/química , Docetaxel/metabolismo , Doxorrubicina/química , Doxorrubicina/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Femenino , Humanos , Irinotecán/química , Irinotecán/metabolismo , Células MCF-7 , Paclitaxel/química , Paclitaxel/metabolismo , Proteoma , Vinorelbina/química , Vinorelbina/metabolismo
8.
Food Funct ; 12(6): 2498-2519, 2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33683257

RESUMEN

Propolis is a by-product of honeybee farming known for its broad therapeutic benefits around the world and is extensively used in the health food and beverage industry. Despite Australia being one of the world's megadiverse countries with rich flora and fauna, Australian propolis samples have not been explored adequately with most in vitro and in vivo studies centred on their Brazilian and Chinese counterparts. In view of this, our study was designed to investigate the chemical composition and anti-proliferative, antibacterial, antifungal, anti-inflammatory and antioxidant properties of Australian propolis (AP-1) extract to draw a comparison with Brazilian (BP-1) and Chinese propolis (CP-1) extracts. The AP-1 extract displayed significantly greater anti-proliferative activity against the MCF7 and the MDA-MB-231 metastatic breast adenocarcinoma cell lines compared to BP-1 and CP-1 (p < 0.05). Similar trends were also observed in the antibacterial (Escherichia coli and Staphylococcus aureus), anti-inflammatory (lipopolysaccharide-induced RAW264.7 macrophages) and antioxidant assays (ABTS, DPPH and CUPRAC) with AP-1 exhibiting more potent activity than BP-1 and CP-1. The ultra-high performance liquid chromatography (UPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (qTOF-MS) and chemometrics implementing unsupervised PCA and supervised OPLS-DA analyses of the propolis samples from Australia, China and Brazil revealed 67 key discriminatory metabolites belonging to seven main chemical classes including flavonoids, triterpenes, acid derivatives, stilbenes, steroid derivatives, diterpenes and miscellaneous compounds. Additionally, seven common phenolic compounds were quantified in the samples. Further mechanistic studies are necessary to elucidate the modes of action of Australian propolis for its prospective use in the food, nutraceutical and pharmaceutical industries.


Asunto(s)
Própolis , Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Australia , Bacterias/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Flavonoides/análisis , Humanos , Células MCF-7 , Espectrometría de Masas , Metaboloma , Fenoles/análisis , Própolis/química , Própolis/metabolismo , Própolis/farmacología
9.
Int J Pharm Compd ; 24(1): 77-82, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32023219

RESUMEN

This study reports on the stability of United States Pharmacopeia-grade metronidazole powder and commercially available metronidazole tablets in two dye-free oral suspending vehicles, namely Oral Mix and Oral Mix Sugar-Free. Metronidazole at 50 mg/mL was prepared individually in Oral Mix and Oral Mix Sugar-Free suspension vehicles and placed in 50-mL amber polyethyleneterephthalate bottles and 3-mL amber plastic syringes and stored at 4°C or 25°C/60% relative humidity for 90 days. The solutions were analyzed at the time of preparation and at 7 days, 14 days, 30 days, 45 days, 60 days, 75 days, and 90 days, with the concentration of metronidazole measured by high-performance liquid chromatography with photodiode array detection. The oral solutions were also monitored for pH, homogeneity, color, and odor. Except for the Oral Mix suspension of metronidazole prepared from the United States Pharmacopeia-grade powder and from the commercial tablet, when stored in pre-filled syringes, all the other preparations were stable at 4°C or 25°C/60% relative humidity for 90 days, with the metronidazole remaining within ± 10% of the initial concentration. The pH, color, odor, and resuspendability remained essentially unchanged. Metronidazole in Oral Mix and Oral Mix Sugar-Free oral suspensions, compounded from United States Pharmacopeia-grade powder or commercially available tablets, are a suitable alternative as an extemporaneously prepared medication.


Asunto(s)
Metronidazol , Administración Oral , Cromatografía Líquida de Alta Presión , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Suspensiones , Comprimidos/administración & dosificación , Estados Unidos
10.
Antioxidants (Basel) ; 8(10)2019 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-31554332

RESUMEN

Persea americana, commonly known as avocado, has recently gained substantial popularity and is often marketed as a "superfood" because of its unique nutritional composition, antioxidant content, and biochemical profile. However, the term "superfood" can be vague and misleading, as it is often associated with unrealistic health claims. This review draws a comprehensive summary and assessment of research performed in the last few decades to understand the nutritional and therapeutic properties of avocado and its bioactive compounds. In particular, studies reporting the major metabolites of avocado, their antioxidant as well as bioavailability and pharmacokinetic properties, are summarized and assessed. Furthermore, the potential of avocado in novel drug discovery for the prevention and treatment of cancer, microbial, inflammatory, diabetes, and cardiovascular diseases is highlighted. This review also proposes several interesting future directions for avocado research.

11.
Molecules ; 24(8)2019 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-30999707

RESUMEN

Background-The quality control (QC) for commercial herbal formulations is sparse due to a lack of well-developed HPLC-ESI-MS/MS methods. Objective-This study reports the quantification of nine selected analytes for a commercial eight-herb formulation known as Qi Ju Di Huang Wan (QJDHW) used to relieve hypertension. Methods-An HPLC-ESI/MS method for the quantitation of analytes selected using the Herbal Chemical Marker Ranking System (Herb MaRS) was developed. The Herb MaRS ranking system which takes into account bioavailability, bioactivity, and physiological action related to its intended use and the commercial availability of the standard. After a method optimization, seven analytes were found to be ideal for quantitation. Results-The target analytes were identified using an electrospray ionization-tandem MS molecular breakdown comparison between the herbal peak and the commercial standard. The quantitative aspect of analyte variability of eleven samples was studied using fold variation. The fold variation of selected analytes among eleven samples ranged from 1.5 to 28.9. The qualitative aspect of variability was studied using principal component analysis (PCA) and hierarchical cluster analysis (HCA). Conclusions-There is a great degree of chemical variability in herbal formulations which are due to raw material harvesting times, storage techniques, and plant subspecies variability. Highlights-Commercial QJDHW formulations need to be standardised using HPLC-ESI-MS/MS to ensure better product quality control (QC) and product efficacy for the consumer.


Asunto(s)
Antihipertensivos/análisis , Medicamentos Herbarios Chinos/análisis , Hipertensión/tratamiento farmacológico , Control de Calidad , Astragalus propinquus , Cromatografía Líquida de Alta Presión/métodos , Humanos , Espectrometría de Masas en Tándem/métodos
12.
Molecules ; 24(6)2019 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-30897753

RESUMEN

The Naoxinqing (NXQ) tablet is a standardised proprietary herbal product containing an extract of persimmon leaves (Diospyros kaki) for the management of cardio- and cerebrovascular diseases. Although previous reports suggested that the efficacy of NXQ is at least partly mediated by its anti-oxidative property, the anti-oxidative effect of the major components of NXQ has not been studied systematically. For quality control purposes, only analytical methods limited to 3 marker analytes have been reported, the extent to which the other components affect efficacy has not been explored. In this study, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC MS/MS) method for the identification of seven analytes (kaempferol-3-O-glucoside (astragalin), quercetin-3-O-galactoside (hypericin), quercetin-3-O-glucoside (isoquercitin), kaempferol, 3,4-dihydroxybenzoic acid (protocatechuic acid), and furan-2-carboxylic acid (pyromucic acid) and quercetin) in the NXQ. This is the first method reported and validated for the quantification of the seven major secondary metabolites in NXQ. The results for the quantified analytes were then compared in 15 different batches of NXQ. The variation observed in the seven components highlights the need to quantify key bioactive components to ensure product consistency. Radical scavenging activity and abundance was used to rank the analytes. The anti-oxidative effects of NXQ were examined using cultured human vascular endothelial cells (EA.hy926). Corrected 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) activity results revealed that quercetin and kaempferol have the strongest anti-oxidant capacity in the extract. Both quercetin and kaempferol significantly inhibited the hydrogen peroxide (H2O2)-induced EA.hy926 cell injury and intracellular reactive oxygen species (ROS) generation. In conclusion, we established and validated an UPLC-MS/MC method for the analysis of major bioactive components in the NXQ and demonstrated that its anti-oxidative property may play a critical role in cerebrovascular protection.


Asunto(s)
Diospyros/química , Medicamentos Herbarios Chinos/química , Extractos Vegetales/química , Hojas de la Planta/química , Antracenos , Línea Celular , Cromatografía Líquida de Alta Presión , Humanos , Hidroxibenzoatos/química , Quempferoles/química , Perileno/análogos & derivados , Perileno/química , Quercetina/análogos & derivados , Quercetina/química , Especies Reactivas de Oxígeno , Espectrometría de Masas en Tándem
13.
Molecules ; 21(11)2016 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-27845729

RESUMEN

Chronic inflammation is an important pathological condition in many human diseases, and due to the side effects of the currently used non-steroidal anti-inflammatory drugs, discovery of novel anti-inflammatory drugs is of general interest. Anti-inflammatory activity guided compound isolation from the plant Alphitonia petriei led to the isolation of the known plant sterols emmolic acid (1), alphitolic acid (2), trans- and cis-coumaroyl esters of alphitolic acid (3 and 4) and betulinic acid (5). A detailed spectroscopic analysis led to the structure elucidation of the alphitolic acid derivatives (1-5), and the semi-synthetic emmolic acid acetate (6). When tested in LPS (Lipopolysaccharides) + IFN-γ (Interferon gamma) activated RAW 264.7 macrophages, all compounds except (1) exhibited potent anti-inflammatory activity (IC50 values as low as 1.7 µM) in terms of downregulation of NO and TNF-α production, but also demonstrated some considerable cytotoxicity.


Asunto(s)
Antiinflamatorios/química , Extractos Vegetales/química , Rhamnaceae/química , Animales , Antiinflamatorios/farmacología , Australia , Productos Biológicos/química , Productos Biológicos/farmacología , Línea Celular , Citocinas/metabolismo , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacología , Bosque Lluvioso , Árboles
14.
Biomed Res Int ; 2016: 5758195, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27830149

RESUMEN

Aims. This study aims to investigate the possible synergistic interactions of the Danshen-Sanqi combination on vascular disease via their anti-inflammatory activities. Methods. Nine combination ratios of Danshen-Sanqi extracts were screened in the RAW264.7 cell line and their anti-inflammatory effects were examined in lipopolysaccharide- (LPS-) induced nitric oxide (NO), tumor necrosis factor (TNF), and monocyte chemoattractant protein-1 (MCP-1) generation pathways. The interaction between Danshen and Sanqi on each target was analysed using combination index (CI) and isobologram models. Additionally, the anti-inflammatory activities of key bioactive compounds from Danshen and Sanqi were tested using the same models. The compounds from each herb that exerted the most potent activity were combined to evaluate their possible synergistic/antagonistic interactions. Results. Danshen-Sanqi 8 : 2 was found to be the optimal ratio and exerted a synergistic effect in inhibiting NO, TNF, and MCP-1 when the concentrations were higher than 1.24, 1.89, and 2.17 mg/mL, respectively. Although dihydrotanshinone I (DT) and ginsenoside Rd (Rd) from Danshen and Sanqi, respectively, exhibited the greatest individual bioactivity in the assays, antagonistic effects were observed for the DT-Rd combination 7 : 3. Conclusion. This study provided scientific evidence to support the traditional use of the Danshen-Sanqi combination for vascular disease through their synergistic interactions on anti-inflammatory pathways.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Mediadores de Inflamación/inmunología , Salvia miltiorrhiza/química , Animales , Citocinas/inmunología , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Sinergismo Farmacológico , Factores Inmunológicos/inmunología , Ratones , Células RAW 264.7 , Resultado del Tratamiento
15.
BMC Complement Altern Med ; 15: 18, 2015 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-25888070

RESUMEN

BACKGROUND: The anti-inflammatory activity of Andrographis paniculata (Acanthaceae), a traditional medicine widely used in Asia, is commonly attributed to andrographolide, its main secondary metabolite. Commercial A. paniculata extracts are standardised to andrographolide content. We undertook the present study to investigate 1) how selective enrichment of andrographolide in commercial A. paniculata extracts affects the variability of non-standardised phytochemical components and 2) if variability in the non-standardised components of the extract affects the pharmacological activity of andrographolide itself. METHODS: We characterized 12 commercial, standardised (≥30% andrographolide) batches of A. paniculata extracts from India by HPLC profiling. We determined the antioxidant capacity of the extracts using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, oxygen radical antioxidant capacity (ORAC) and a Folin-Ciocalteu (FC) antioxidant assays. Their anti-inflammatory activity was assessed by assaying their inhibitory effect on the release of tumor necrosis factor alpha (TNF-α) in the human monocytic cell line THP-1. RESULTS: The andrographolide content in the samples was close to the claimed value (32.2 ± 2.1%, range 27.5 to 35.9%). Twenty-one non-standardised constituents exhibited more than 2-fold variation in HPLC peak intensities in the tested batches. The chlorogenic acid content of the batches varied more than 30-fold. The DPPH free radical scavenging activity varied ~3-fold, the ORAC and FC antioxidant capacity varied ~1.5 fold among batches. In contrast, the TNF-α inhibitory activity of the extracts exhibited little variation and comparison with pure andrographolide indicated that it was mostly due to their andrographolide content. CONCLUSIONS: Standardised A. paniculata extracts contained the claimed amount of andrographolide but exhibited considerable phytochemical background variation. DPPH radical scavenging activity of the extracts was mostly due to the flavonoid/phenlycarboxylic acid compounds in the extracts. The inhibitory effect of andrographolide on the release of TNF-α was little affected by the quantitative variation of the non-standardised constituents.


Asunto(s)
Andrographis/química , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Diterpenos/farmacología , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Compuestos de Bifenilo/metabolismo , Ácido Clorogénico/análisis , Ácido Clorogénico/farmacología , Cromatografía Líquida de Alta Presión , Diterpenos/análisis , Flavonoides/análisis , Flavonoides/farmacología , Humanos , Técnicas In Vitro , India , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Picratos/metabolismo , Extractos Vegetales/normas
16.
Eur J Nutr ; 53(1): 335-43, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23653285

RESUMEN

PURPOSE: Chronic inflammatory processes contribute to the pathogenesis of many age-related diseases. In search of anti-inflammatory foods, we have systematically screened a variety of common dietary plants and mushrooms for their anti-inflammatory activity. METHODS: A selection of 115 samples was prepared by a generic food-compatible processing method involving heating. These products were tested for their anti-inflammatory activity in murine N11 microglia and RAW 264.7 macrophages, using nitric oxide (NO) and tumour necrosis factor-α (TNF-α) as pro-inflammatory readouts. RESULTS: Ten food samples including lime zest, English breakfast tea, honey-brown mushroom, button mushroom, oyster mushroom, cinnamon and cloves inhibited NO production in N11 microglia, with IC50 values below 0.5 mg/ml. The most active samples were onion, oregano and red sweet potato, exhibiting IC50 values below 0.1 mg/ml. When these ten food preparations were retested in RAW 264.7 macrophages, they all inhibited NO production similar to the results obtained in N11 microglia. In addition, English breakfast tea leaves, oyster mushroom, onion, cinnamon and button mushroom preparations suppressed TNF-α production, exhibiting IC50 values below 0.5 mg/ml in RAW 264.7 macrophages. CONCLUSION: In summary, anti-inflammatory activity in these food samples survived 'cooking'. Provided that individual bioavailability allows active compounds to reach therapeutic levels in target tissues, these foods may be useful in limiting inflammation in a variety of age-related inflammatory diseases. Furthermore, these foods could be a source for the discovery of novel anti-inflammatory drugs.


Asunto(s)
Agaricales/química , Alimentos , Inflamación , Animales , Línea Celular Tumoral , Supervivencia Celular , Culinaria , Concentración 50 Inhibidora , Macrófagos/metabolismo , Ratones , Microglía/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/metabolismo
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