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1.
J Chromatogr A ; 1725: 464909, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38688052

ABSTRACT

Membrane technology has revolutionized various fields with its energy efficiency, versatility, user-friendliness, and adaptability. This study introduces a microfluidic chip, comprised of silicone rubber and polymethylmethacrylate (PMMA) sheets to explore the impacts of polymeric support morphology on electro-membrane extraction efficiency, representing a pioneering exploration in this field. In this research, three polyvinylidenefluoride (PVDF) membranes with distinct pore sizes were fabricated and their characteristics were assessed through field-emission scanning electron microscopy (FESEM), and atomic force microscopy (AFM). This investigation centers on the extraction of three widely prescribed non-steroidal anti-inflammatory drugs: aspirin (ASA), naproxen (NAP), and ibuprofen (IBU). Quantitative parameters in the extraction process including voltage, donor phase flow rate, and acceptor phase composition were optimized, considering the type of membrane as a qualitative factor. To assess the performance of the fabricated PVDF membranes, a comparative analysis with a commercially available Polypropylene (PP) membrane was conducted. Efficient enrichment factors of 30.86, 23.15, and 21.06 were attained for ASA, NAP, and IBU, respectively, from urine samples under optimal conditions using the optimum PVDF membrane. Significantly, the choice of the ideal membrane amplified the purification levels of ASA, NAP, and IBU by factors of 1.6, 7.5, and 40, respectively.


Subject(s)
Ibuprofen , Membranes, Artificial , Polyvinyls , Polyvinyls/chemistry , Ibuprofen/isolation & purification , Ibuprofen/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Humans , Naproxen/isolation & purification , Naproxen/chemistry , Aspirin/chemistry , Aspirin/isolation & purification , Microfluidic Analytical Techniques , Limit of Detection , Fluorocarbon Polymers
2.
J Chromatogr A ; 1724: 464924, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38653038

ABSTRACT

This work, reports the successful preparation a thin film by a simple and inexpensive process for quantification of a model analytes in the urine sample using HPLC-UV. To this end, cellulose paper was employed as a substrate for the in-situ synthesis of MOF-5, to increase the resistance of the prepared film. The prepared film can be reused 26 times with no reduction in its performance. The thin film prepared by MOF-5 modified cellulose substrate was utilized in thin film microextraction (TFME) method for the extraction and preconcentration of naproxen, aspirin, tolmetin, and celecoxib. Under optimal conditions, the linear dynamic range of the target analytes was 2-500 µg L-1 with correlation coefficients (R2) ranging from 0.9961 to 0.9990. Also, the limits of detection (LODs), the limits of quantification (LOQs) and relative standard deviation (RSD%) of the proposed method for selected analytes ranged between 0.57 and 0.77 µg L-1, 1.7 to 2.3 and 3.5 % to 6.2 %, respectively. Moreover, relative recoveries varied from of 94 % to 108 %, indicating the absence of matrices effect in the proposed method. Eventually, the TFME was successfully used for the extraction of selected analytes from urine samples.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Cellulose , Limit of Detection , Metal-Organic Frameworks , Solid Phase Microextraction , Chromatography, High Pressure Liquid/methods , Cellulose/chemistry , Metal-Organic Frameworks/chemistry , Humans , Anti-Inflammatory Agents, Non-Steroidal/urine , Anti-Inflammatory Agents, Non-Steroidal/analysis , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Solid Phase Microextraction/methods , Reproducibility of Results
3.
Chem Biodivers ; 21(5): e202302111, 2024 May.
Article in English | MEDLINE | ID: mdl-38453650

ABSTRACT

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.


Subject(s)
Anti-Inflammatory Agents , Molecular Docking Simulation , Nitric Oxide , Solanum , Solanum/chemistry , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cyclooxygenase 2/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Network Pharmacology , Amides/chemistry , Amides/pharmacology , Amides/isolation & purification , Mice , Dose-Response Relationship, Drug , Molecular Structure , Structure-Activity Relationship , Cell Line , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification
4.
Phytochemistry ; 222: 114052, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38518849

ABSTRACT

A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.


Subject(s)
Diterpenes , Ergosterol , Reishi , Mice , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Animals , RAW 264.7 Cells , Reishi/chemistry , Ergosterol/pharmacology , Ergosterol/analogs & derivatives , Ergosterol/chemistry , Ergosterol/isolation & purification , Molecular Structure , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Cyclooxygenase 2/metabolism , Structure-Activity Relationship , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Dose-Response Relationship, Drug , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Down-Regulation/drug effects
5.
Proc Natl Acad Sci U S A ; 119(22): e2122506119, 2022 05 31.
Article in English | MEDLINE | ID: mdl-35622893

ABSTRACT

BRDT, BRD2, BRD3, and BRD4 comprise the bromodomain and extraterminal (BET) subfamily which contain two similar tandem bromodomains (BD1 and BD2). Selective BD1 inhibition phenocopies effects of tandem BET BD inhibition both in cancer models and, as we and others have reported of BRDT, in the testes. To find novel BET BD1 binders, we screened >4.5 billion molecules from our DNA-encoded chemical libraries with BRDT-BD1 or BRDT-BD2 proteins in parallel. A compound series enriched only by BRDT-BD1 was resynthesized off-DNA, uncovering a potent chiral compound, CDD-724, with >2,000-fold selectivity for inhibiting BRDT-BD1 over BRDT-BD2. CDD-724 stereoisomers exhibited remarkable differences in inhibiting BRDT-BD1, with the R-enantiomer (CDD-787) being 50-fold more potent than the S-enantiomer (CDD-786). From structure­activity relationship studies, we produced CDD-956, which maintained picomolar BET BD1 binding potency and high selectivity over BET BD2 proteins and had improved stability in human liver microsomes over CDD-787. BROMOscan profiling confirmed the excellent pan-BET BD1 affinity and selectivity of CDD-787 and CDD-956 on BD1 versus BD2 and all other BD-containing proteins. A cocrystal structure of BRDT-BD1 bound with CDD-956 was determined at 1.82 Å and revealed BRDT-BD1­specific contacts with the αZ and αC helices that explain the high affinity and selectivity for BET BD1 versus BD2. CDD-787 and CDD-956 maintain cellular BD1-selectivity in NanoBRET assays and show potent antileukemic activity in acute myeloid leukemia cell lines. These BET BD1-specific and highly potent compounds are structurally unique and provide insight into the importance of chirality to achieve BET specificity.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Antineoplastic Agents , Contraceptive Agents, Male , Drug Discovery , Nuclear Proteins , Small Molecule Libraries , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Contraceptive Agents, Male/chemistry , Contraceptive Agents, Male/isolation & purification , Contraceptive Agents, Male/pharmacology , DNA/genetics , Humans , Male , Nuclear Proteins/antagonists & inhibitors , Nuclear Proteins/chemistry , Protein Domains , Small Molecule Libraries/chemistry , Small Molecule Libraries/isolation & purification , Small Molecule Libraries/pharmacology , Structure-Activity Relationship
6.
Sci Rep ; 12(1): 2152, 2022 02 09.
Article in English | MEDLINE | ID: mdl-35140310

ABSTRACT

Long-term exposure to air pollution has been associated with the development of some inflammatory processes related to skin. The goal of modern medicine is the development of new products with antiflammatory action deriving from natural sources to improve environmental and economic sustainability. In this study, two different humic acids (HA) were isolated from from lignite (HA-LIG) and composted artichoke wastes (HA-CYN) and characterized by infrared spectrometry, NMR spectroscopy, thermochemolysis-GC/MS, and high-performance size-exclusion chromatography (HPSEC), while their antiflammatory activity was evaluated on HaCaT cells. Spectroscopic results showing the predominance of apolar aliphatic and aromatic components in HA-LIG, whereas HA-CYN revealed a presence of polysaccharides and polyphenolic lignin residues. The HA application on human keratinocyte pre-treated with Urban Dust revealed a general increase of viability suggesting a protective effect of humic matter due to the content of aromatic, phenolic and lignin components. Conversely, the gene expression of IL-6 and IL-1ß cytokines indicated a significant decrease after application of HA-LIG, thus exhibiting a greater antiflammatory power than HA-CYN. The specific combination of HA protective hydrophobic components, viable conformational arrangements, and content of bioactive molecules, suggests an innovative applicability of humic matter in dermatology as skin protectors from environmental irritants and as antiflammatory agents.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Coal , Composting , Humic Substances , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Cell Survival , Chromatography, Gel , Coal/analysis , Gas Chromatography-Mass Spectrometry , HaCaT Cells , Humans , Humic Substances/analysis , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Keratinocytes/cytology , Magnetic Resonance Spectroscopy
7.
Chem Pharm Bull (Tokyo) ; 70(1): 66-73, 2022.
Article in English | MEDLINE | ID: mdl-34980736

ABSTRACT

Despite the precise mechanisms for renal ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) are poorly understood, nuclear factor erythroid 2 related factor 2 (Nrf2) and Toll-like receptor 4 (TLR4) pathways were considered as the important targets. Leonurine (LEO) is a special alkaloid extracted from Chinese motherwort (Leonurus japonicus Houtt), which has an anti-inflammatory effect and reduces oxidative stress. We conducted the study to explore the efficacy of LEO against I/R-induced AKI in rats and further investigated the underlying mechanisms. Ischemic renal injury was induced by temporary vascular clamping for 45 min. We have measured the levels of inflammation-related biomarkers and antioxidative stress markers. Next, Western blot analysis and Real-time PCR were performed to analyze whether the Nrf2 and TLR4/nuclear factor-kappaB (NF-κB) pathways were involved in this process. We found that LEO pretreatment remarkably decreased serum creatinine and blood urea nitrogen (BUN) in I/R rats and attenuated acute tubular damage. In addition, LEO markedly increased the expression of antioxidant proteins and decreased the levels of inflammatory factors. Further study revealed that LEO promoted Nrf2 into the nucleus, promoted the expression of heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1), and suppressed the TLR4/NF-κB signal pathway in kidney tissues of ischemic AKI rats. The study reveals that LEO has a protective effect to prevent ischemic AKI through activation of Nrf2 nuclear translocation resisting oxidative stress injury and inhibition of the TLR4/NF-κB pathway mediated inflammatory gene expression.


Subject(s)
Acute Kidney Injury/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Gallic Acid/analogs & derivatives , Leonurus/chemistry , NF-E2-Related Factor 2/metabolism , NF-kappa B/antagonists & inhibitors , Toll-Like Receptor 4/antagonists & inhibitors , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Gallic Acid/chemistry , Gallic Acid/isolation & purification , Gallic Acid/pharmacology , Injections, Intraperitoneal , Male , Molecular Structure , NF-kappa B/metabolism , Pentobarbital/administration & dosage , Rats , Rats, Sprague-Dawley , Toll-Like Receptor 4/metabolism
8.
Bioorg Chem ; 119: 105538, 2022 02.
Article in English | MEDLINE | ID: mdl-34929516

ABSTRACT

Baicalin has distinct therapeutic effects in various skin diseases animal models such as atopic dermatitis (AD) and psoriasis. In this study, we aimed to investigate the anti-atopic dermatitis (AD) effects of baicalin in 2,4-dinitrochlorobenzene (DNCB)-treated mice. Female BALB/c mice treated with DNCB to induce AD-like skin lesions and orally administrated with baicalin daily for 14 consecutive days. Baicalin significantly inhibited dorsal skin thickness and trans-epidermal water loss and epidermal thickness in dorsal skin. In addition, baicalin also significantly up-regulated the protein expressions of filaggrin, involucrin, and loricrin, but inhibited the inflammatory response and the activation of NF-κB and JAK/STAT pathways in the dorsal skin of the DNCB-treated mice. Furthermore, baicalin significantly restored the abundance of probiotics in the gut microbiota of the DNCB-treated mice. Pseudo germ-free (GF) DNCB-treated mice receiving fecal microbiota from baicalin donors reduced the dorsal skin thickness and skin EASI score, and inhibited the release of IgE, histamine, TNF-α and IL-4 in serum of mice. In summary, baicalin ameliorates AD-like skin lesions induced by DNCB in mice via regulation of the Th1/Th2 balance, improvement of skin barrier function and modulation of gut dysbiosis, and inhibition of inflammation through suppressing the activation of NF-κB and JAK/STAT pathways.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Dermatitis, Atopic/drug therapy , Flavonoids/pharmacology , Skin/drug effects , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Dermatitis, Atopic/chemically induced , Dinitrochlorobenzene , Dose-Response Relationship, Drug , Female , Flavonoids/chemistry , Flavonoids/isolation & purification , Gastrointestinal Microbiome/drug effects , Janus Kinases/antagonists & inhibitors , Janus Kinases/metabolism , Mice , Mice, Inbred BALB C , Molecular Structure , Plant Roots/chemistry , STAT Transcription Factors/antagonists & inhibitors , STAT Transcription Factors/metabolism , Scutellaria baicalensis/chemistry , Skin/metabolism , Skin/pathology , Structure-Activity Relationship
9.
Bioorg Chem ; 119: 105577, 2022 02.
Article in English | MEDLINE | ID: mdl-34959178

ABSTRACT

Phallus rubrovolvatus is an important commercially cultivated mushroom species in China. However, the volva of P. rubrovolvatus usually discarded as a by-product due to the unpleasant flavor and difficulty in processing. In this study, we investigated the chemical constituents and bioactivities of the volva of P. rubrovolvatus. As a result, fifteen rare aniline derivatives, including twelve new compounds (1-11, 14) and three new natural products (12, 13, 15) were isolated from the volva. Their structures were determined using 1D and 2D NMR data and HR-ESI-MS data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In addition, compounds 1-15 were tested for anti-inflammatory activity against lipopolysaccharide (LPS)-induced NO production in RAW264.7 macrophages. Compounds 4, 9 and 10 exhibited anti-inflammatory activity with IC50 values ranging from 12.5 to 15.6 µM.


Subject(s)
Aniline Compounds/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Basidiomycota/chemistry , Nitric Oxide/antagonists & inhibitors , Plant Extracts/pharmacology , Waste Products/analysis , Aniline Compounds/chemistry , Aniline Compounds/isolation & purification , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Dose-Response Relationship, Drug , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Plant Extracts/chemistry , Plant Extracts/isolation & purification , RAW 264.7 Cells , Structure-Activity Relationship
10.
Bioorg Chem ; 119: 105522, 2022 02.
Article in English | MEDLINE | ID: mdl-34864279

ABSTRACT

Six new lignans with various type of linkage between two C6-C3 fragments (1a, 1b, 2a, 2b, 3, 4), two new meroterpenoids (5, 6) and 24 known compounds (7-30) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of enantiomers 1a and 1b were determined by single-crystal X-ray diffraction analysis, 2a and 2b were determined by comparing their calculated and experimental ECD spectra. Biogenetically, all the new lignans may come from the polymerization of two molecules of hydroxychavicol (30). In the anti-neuroinflammation activity assay, the IC50 values of fifteen compounds were lower than those of the positive control minocycline, and compound 1a showed good activity, but its enantiomer 1b showed no activity. Compound 1a have notable anti-neuroinflammatory activity, and can significantly decrease mRNA levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in a dose-dependent manner.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Lignans/pharmacology , Nitric Oxide/antagonists & inhibitors , Piper/chemistry , Plant Extracts/pharmacology , Terpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cell Line , Crystallography, X-Ray , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Dose-Response Relationship, Drug , Lignans/chemistry , Lignans/isolation & purification , Mice , Models, Molecular , Molecular Structure , Nitric Oxide/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , RNA, Messenger/antagonists & inhibitors , RNA, Messenger/metabolism , Stereoisomerism , Structure-Activity Relationship , Terpenes/chemistry , Terpenes/isolation & purification
11.
Fitoterapia ; 156: 105068, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34715153

ABSTRACT

Three labdane-type [multisins A-C (1-3)], two guaiane-type [multisins D (4) and E (5)], and one eudesmane-type [multisin F (6)] previously undescribed terpenoids, together with 14 mono- (7-20) and seven dimeric- (21-27) known terpenoids, were isolated from the 90% MeOH extract of the whole plant of Chloranthus multistachys. Their structures and absolute configurations were determined by extensive spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 are rare trinor-sesquiterpenes with a de-isopropyl guaiane skeleton, whereas compound 6 is a rearranged dinor-eudesmene featuring an uncommon octahydro-1H-indene ring system. Among the isolates, the dimeric lindenane sesquiterpenoid shizukaol C (25) exhibited the most potent (IC50 = 8.04 µM) anti-neuroinflammatory activity by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Magnoliopsida/chemistry , Plant Extracts/pharmacology , Terpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Biological Assay , Cell Line , China , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mice , Microglia/cytology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Oils/chemistry , Plant Oils/pharmacology , Plant Roots/chemistry , Structure-Activity Relationship , Terpenes/chemistry
12.
Bioorg Med Chem ; 51: 116495, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34781083

ABSTRACT

Four new 19-nor-clerodane diterpenoids (1-4), one new 15,16-dinor-ent-pimarane diterpenoid (5) together with four known diterpenoids (6-9) were isolated from whole plants of Croton yunnanensis. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparing their NMR data with those of previously reported compounds. The experimental and calculated electronic circular dichroism data were used to define their absolute configurations. The 1H and 13C NMR spectra of 6 were completely assigned for the first time. All isolated compounds (1-9) were evaluated for their cytotoxic activities against five human cancer cell lines (including SMMC-7721, HL-60, A-549, MCF-7, and SW-480), and anti-inflammatory activities in LPS-induced RAW264.7 macrophages. Crotonyunnan E (5) exhibited selective cytotoxicities against three tumor cell lines, SMMC-7721 (human hepatoma cells, IC50 4.47 ± 0.39 µM), HL-60 (human premyelocytic leukemia, IC50 14.38 ± 1.19 µM), and A-549 (human lung cancer cells, IC50 27.42 ± 0.48 µM), while none of the compounds showed obviously anti-inflammatory activities at 50 µM level.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Croton/chemistry , Diterpenes/pharmacology , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Density Functional Theory , Diterpenes/chemistry , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Plant Extracts/chemistry , Plant Extracts/isolation & purification , RAW 264.7 Cells , Structure-Activity Relationship
13.
Chem Biodivers ; 18(12): e2100518, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34705327

ABSTRACT

In this study, the following compounds were isolated from the dichloromethane fraction of the stems of Amomum longiligulare and then characterized: a new benzofuran, namely, longifuran A (1); five other phenolic compounds, namely, 4-methoxycinnamic acid (2), 2,5-dimethoxyphenol (3), eudesmic acid (4), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (5), and 4,4'-dihydroxychalcone (6); and two triterpenoids, namely, 24-methylcycloartan-3ß-ol (7) and 24-methylencycloartan-3ß-ol (8). They were evaluated in terms of their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages. Results indicated that 1 and 5 exhibited promising inhibitory activities against NO generation with IC50 of 10.47±1.02 µM and 8.51±1.14 µM, respectively. Enzymatic assays demonstrated that they remarkably suppressed the secretion of two pro-inflammatory cytokines (i. e., IL-6 and TNF-α). They also dose-dependently inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2, two important enzymes modulating inflammation. Therefore, 1 and 5 could be targets for the development of new anti-inflammatory therapeutics.


Subject(s)
Amomum/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Benzofurans/pharmacology , Plant Stems/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Benzofurans/chemistry , Benzofurans/isolation & purification , Dose-Response Relationship, Drug , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , RAW 264.7 Cells
14.
Bioorg Chem ; 116: 105338, 2021 11.
Article in English | MEDLINE | ID: mdl-34521045

ABSTRACT

Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (1-4) with an unprecedented spiro[furo[3,2-b]benzofuran-3,2'-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, 13C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC50 value of 7.93 µM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 µM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-ß (C/EBP-ß), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Ganoderma/chemistry , Lipogenesis/drug effects , Receptors, Formyl Peptide/antagonists & inhibitors , Receptors, Lipoxin/antagonists & inhibitors , Terpenes/pharmacology , 3T3-L1 Cells , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Mice , Molecular Dynamics Simulation , Molecular Structure , PPAR gamma/antagonists & inhibitors , PPAR gamma/metabolism , Receptors, Formyl Peptide/genetics , Receptors, Formyl Peptide/metabolism , Receptors, Lipoxin/genetics , Receptors, Lipoxin/metabolism , Structure-Activity Relationship , Terpenes/chemistry , Terpenes/isolation & purification
15.
Chem Biodivers ; 18(12): e2100631, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34586715

ABSTRACT

The genus Doronicum, belonging to tribe Senecioneae (Fam. Asteraceae), is found mainly in the Asia, Europe and North Africa. This genus of plant has always been used in traditional medicinal treatments due to the many biological properties shown such as killing parasitic worms and for relieving constipation, as well as to improve heart health, to alleviate pain and inflammation, to treat insect bites, etc. According to the World Flora the genus Doronicum contains 39 subordinate taxa.[1-3] The purpose of this article, which covers data published from 1970 to 2021 with more than 110 articles, aims to carry out a complete and critical review of the Doronicum genus, examining traditional uses and reporting the antioxidant, antimicrobial, anti-inflammatory and antitumor activity shown from crude extracts or essential oils, and from single isolated compounds. Furthermore, critical considerations of the published data have been highlighted by comparing them with the results obtained from species of other genus belonging to the Asteraceae family.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Asteraceae/chemistry , Pyrrolizidine Alkaloids/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/chemistry , Antioxidants/isolation & purification , Humans , Molecular Structure , Pyrrolizidine Alkaloids/chemistry , Pyrrolizidine Alkaloids/isolation & purification
16.
Naunyn Schmiedebergs Arch Pharmacol ; 394(11): 2167-2185, 2021 11.
Article in English | MEDLINE | ID: mdl-34542667

ABSTRACT

The link between diabetes and cognitive dysfunction has been reported in many recent articles. There is currently no disease-modifying treatment available for cognitive impairment. Boswellia serrata (B. serrata) is used traditionally to treat chronic inflammatory diseases such as type 2 diabetes (T2D), insulin resistance (IR), and Alzheimer's disease (AD). This review aims to highlight current research on the potential use of boswellic acids (BAs)/B. serrata extract in T2D and AD. We reviewed the published information through June 2021. Studies have been collected through a search on online electronic databases (Academic libraries as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Accumulating evidence in preclinical and small human clinical studies has indicated that BAs/B. serrata extract has potential therapeutic effect in T2D and AD. According to most of the authors, the potential therapeutic effects of BAs/B. serrata extract in T2D and AD can be attributed to immunomodulatory, anti-inflammatory, antioxidant activity, and elimination of the senescent cells. BAs/B. serrata extract may act by inhibiting the IκB kinase/nuclear transcription factor-κB (IKK/NF-κB) signaling pathway and increasing the formation of selective anti-inflammatory LOX-isoform modulators. In conclusion, BAs/B. serrata extract may have positive therapeutic effects in prevention and therapy of T2D and AD. However, more randomized controlled trials with effective, large populations are needed to show a definitive conclusion about therapeutic efficacy of BAs/B. serrata extract in T2D and AD.


Subject(s)
Boswellia/chemistry , Plant Extracts/pharmacology , Triterpenes/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/physiopathology , Alzheimer Disease/prevention & control , Animals , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/isolation & purification , Antioxidants/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/prevention & control , Humans , Immunomodulating Agents/isolation & purification , Immunomodulating Agents/pharmacology , Randomized Controlled Trials as Topic , Triterpenes/isolation & purification
17.
J Chromatogr A ; 1654: 462453, 2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34392125

ABSTRACT

A novel microchip electrophoresis method with conductivity detection for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in several pharmaceutical formulations was developed. The three frequently used NSAIDs - acetylsalicylic acid, diclofenac and ibuprofen were baseline separated on a poly(methyl methacrylate) microchip with coupled separation channels. Elimination of matrix components such as excipients, was realized through online combination of isotachophoresis (ITP) with zone electrophoresis (ZE). ITP-ZE hyphenation can also facilitate preconcentration of target analytes. ITP was carried out in the first separation channel at pH 6.5, while the second channel of the microchip was used for ZE separation and detection of the analytes at pH 7.0. The developed ITP-ZE method was demonstrated to be applicable for direct and reliable determination of NSAIDs in eleven pharmaceutical formulations. The noticeable advantage of this approach is that only simple sample pretreatment (filtration and dilution) is necessary. The method performance parameters, such as linearity (20-250% of nominal concentration of studied NSAIDs in the test samples), accuracy (98-102%) and precision (less than 2% RSD) were obtained. This universal approach is suitable for the determination of frequently used NSAIDs in a single analysis in less than 15 min. In addition to simple sample pretreatment, low running costs and minimal environmental impact could make this method attractive for the analysis of pharmaceutical preparations.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Chemistry, Pharmaceutical , Electrophoresis, Microchip , Pharmaceutical Preparations , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Chemistry, Pharmaceutical/methods , Electric Conductivity , Isotachophoresis , Pharmaceutical Preparations/chemistry
18.
Bioorg Chem ; 115: 105246, 2021 10.
Article in English | MEDLINE | ID: mdl-34371372

ABSTRACT

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperwilsones A-K (1-11), along with five known PPAPs (12-16), were isolated from Hypericum wilsonii. Their structures were established via spectroscopic methods, the careful analysis of calculated and experimental electronic circular dichroism (ECD) spectra, single-crystal X-ray diffraction, the modified Mosher's method, and [Rh2(OCOCF3)4]-induced ECD. Hyperwilsone A (1) and hyperwilsone B (2) possessed the unique acetal functionality. Hyperwilsone C (3) was a rare example of [3.3.1]-type PPAP possessing a 3-isopropylfuran moiety. In bioassay, compounds 9 and 10 showed potent anti-inflammatory activity against LPS-induced NO production by inhibiting the nuclear translocation of NF-κB p65 and thus reducing the production of proinflammatory cytokines. Compounds 5, 8, 11, and 14 exhibited moderate inhibitory activity against SUDHL-4 and HL60 cancer cells with IC50 values in the range of 5.74-19.82 µM.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Drug Discovery , Hypericum/chemistry , Phloroglucinol/pharmacology , Polycyclic Compounds/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Phloroglucinol/chemistry , Phloroglucinol/isolation & purification , Polycyclic Compounds/chemistry , Polycyclic Compounds/isolation & purification , RAW 264.7 Cells , Structure-Activity Relationship
19.
Future Med Chem ; 13(19): 1679-1694, 2021 10.
Article in English | MEDLINE | ID: mdl-34410182

ABSTRACT

α-Mangostin is a xanthone natural product isolated as a secondary metabolite from the mangosteen tree. It has attracted a great deal of attention due to its wide-ranging effects on certain biological activity, such as apoptosis, tumorigenesis, proliferation, metastasis, inflammation, oxidation, bacterial growth and metabolism. This review focuses on the key pathways directly affected by α-mangostin and how this varies between disease states. Insight is also provided, where investigated, into the key structural features of α-mangostin that produce these biological effects. The review then sheds light on the utility of α-mangostin as a investigational tool for certain diseases and demonstrate how future derivatives may increase selectivity and potency for specific disease states.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Biological Products/pharmacology , Hypoglycemic Agents/pharmacology , Xanthones/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Biological Products/chemistry , Biological Products/isolation & purification , Cell Proliferation/drug effects , Diabetes Mellitus/drug therapy , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Inflammation/drug therapy , Molecular Structure , Xanthones/chemistry , Xanthones/isolation & purification
20.
J Chromatogr A ; 1654: 462464, 2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34438302

ABSTRACT

The effect of adding ethoxylated sorbitan ester surfactants (Tweens®) to poly(ethylene glycol) diacrylate-based monolithic recipes was investigated. Five different Tweens® have been evaluated to investigate the exact role of non-ionic surfactants in poly(ethylene glycol) diacrylate-based monolith preparations. These monoliths were characterized by scanning electron microscopy, infrared spectroscopy, and nitrogen physisorption analysis. Different morphological features, and surface areas were observed when different types of Tween® were included in the recipe; Tween® 20 and 85 showed small globules, while Tween® 40, 60 and 80 exhibited larger globular structures with different sizes and degrees of coalescence. The different Tween®-based monoliths were investigated for the chromatographic separation of mixtures consisting of hydroxybenzoic acids and alkylbenzenes. These columns were mechanically stable, except for Tween® 80. The highest methylene selectivity and the best overall performance were achieved by Tween® 60. The efficiency was increased by increasing the concentration of the Tween® 60 and the amount of poly(ethylene glycol) diacrylate Mn 700 in the recipes up to 30 wt%, each. Further increases in either Tween® 60 or poly(ethylene glycol) diacrylate Mn 700 led to formation of non-permeable columns. The optimized column was successfully used for separation of mixtures of nonsteroidal anti-inflammatory and sulfa drugs, with a maximum efficiency of 60,000 plates/m.


Subject(s)
Chemistry Techniques, Analytical , Chromatography , Esters , Polysorbates , Surface-Active Agents , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Chemistry Techniques, Analytical/methods , Chemistry Techniques, Analytical/standards , Chromatography/instrumentation , Chromatography/standards , Esters/chemistry , Hydroxybenzoates , Polysorbates/chemistry
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