Nitric Oxide Production In RAW Research Articles

Phenolic Acids Derivatives from Meehania Fargesii with Anti-inflammation Effects.

Utilizing systematic plant chemistry separation techniques, two previously unreported phenolic acids (1-2) and eighteen (3-20) phenolic acids were isolated from 70% ethanol extract of Meehania fargesii var. radicans (Vaniot) C.Y.Wu. The structures of the unreported compounds were determined using spectroscopic methods, including 1D and 2D NMR, ECD, and HR-ESI-MS. The activity of all isolated phenolic acids was evaluated for their ability to inhibit nitric oxide (NO) production in RAW264.7 cells activated by lipopolysaccharide (LPS). Among the isolated compounds, compounds 1 and 19 exhibited significant inhibitory activity against NO production in RAW264.7 cells, with higher concentrations being more active than the indomethacin, without displaying cytotoxicity. This study provides a basis for the application and development of M. fargesii and the discovery of natural anti-inflammatory drugs.

Potential active fractions and constituents in the flowers of Trollius chinensis Bunge responsible for treating acute pharyngitis

Ethnopharmacological relevanceTrollius chinensis Bunge has a long history of use in China as traditional Chinese medicine and functional tea for the treatment of respiratory infections, such as pharyngitis, tonsillitis and bronchitis. Pharyngitis can impact the entire throat and adjacent lymphoid tissues, and may lead to significant systemic complications. However, the active components and mechanism of Trollius chinensis Bunge for treating acute pharyngitis remains unclear. Aim of the studyTrollius chinensis Bunge is recognized in China both as a medicinal herb and a functional tea. Research into its properties aimed to establish its effectiveness against pharyngitis and to pinpoint the active components and mechanism. Materials and methodsA 70% ethanol extract from the herb was prepared, which was refined using chromatography through a column containing D101 macroporous resin and varying ethanol solutions. The efficacy of the initial and refined extracts was tested using a rat model of ammonia-induced acute pharyngitis. Pathological examination, HE staining and ELISA were applied to screen activity fraction. The compounds were isolated by silica gel, sephadex LH-20 column chromatography and semi-preparative HPLC chromatography from active fraction. All of the isolated compounds were assessed for anti-inflammatory activity by acting on LPS-induced RAW 264.7 macrophage cells in vitro. Cytotoxicity of compounds was detected by CCK-8 assay. The Griess reaction was applied to evaluate the inhibitory effects of isolated compounds on NO production in RAW 264.7 cells induced by LPS. TNF-α, IL-6, IL-1β and PGE2 levels in macrophage supernatant were detected by ELISA. Molecular docking and western blot analysis were applied to study the anti-inflammatory mechanism of active compound. ResultsThe fraction extracted with 30% ethanol proved particularly effective, significantly reducing pharyngitis symptoms. This was evidenced by decreased levels of cytokines (TNF-α, IL-6, IL-1β and PGE2) and visible improvements in the pharyngeal tissue histology. In pursuit of pharyngitis treatments, 23 phenolic acids and 13 flavonoids were isolated from the 30% ethanol fraction and identified using spectral analysis. Of these, three were newly discovered compounds and eight were first-time isolates from the Trollius genus. These compounds were further investigated for their ability to suppress nitric oxide production in RAW 264.7 cells triggered by lipopolysaccharide. Compounds 3, 19, and 26 exhibited strong anti-inflammatory properties. HPLC analysis of the 30% ethanol fraction revealed that orientin was the predominant component, accounting for 44.4% of this fraction. Western blot analysis demonstrated that orientin reduced the expression levels of the protein p-p65 relative to p65, p-IκBα relative to IκBα and iNOS, indicating an anti-inflammatory effect potentially through the modulation of the NF-κB signaling pathway. ConclusionThe finding of this study provided strong support for the use of T. chinensis as a potential functional food for treating pharyngitis.

Green extraction of marine phospholipids from Conger eel by-product using SC-CO2: Lipidomic profiles and biological activities

This paper presents an eco-friendly approach to recovering phospholipids (PLs) from the Conger myriaster head (CMH) via supercritical carbon dioxide (SC–CO2) extraction using ethanol as a cosolvent. The lipidomic profile and biological activities of the extracted PLs were investigated. Purity assessments, PL composition analysis, and fatty acid profiling were performed to characterize the PLs. Biological activity was determined through antioxidant, antimicrobial, antihypertensive, anti-inflammatory, and anticancer evaluations. The results showed that the yields of the SC–CO2 extracted CMH PLs (SCHP) and organic solvent extracted CMH PLs (OCHP) were 3.26% ± 0.20 % (76.18% ± 0.09% purity) and 9.02% ± 0.21% (purity = 18.29% ± 0.04%), respectively. The 31P NMR analysis revealed a diverse PL composition in both extracts, with the SCHP showing higher PC content and selective extraction characteristics. The SCHP exhibited significantly superior antioxidant, antimicrobial, antihypertensive, and anti-dementia activities compared to the OCHP. Both extracts inhibited nitric oxide production in RAW 264.7 cells, suggesting anti-inflammatory activity. Selective anticancer activity was observed, with high toxicity in SK-N-SH cells but no cytotoxicity in RAW 264.7 and HaCaT cells. The findings highlight the potential of SC-CO2 extraction using ethanol to obtain bioactive PLs from marine by-products, with promising applications in the pharmaceutical, cosmetic, and food industries.

Phyllanretiosides A and B: Two Undescribed Compounds from Phyllanthus reticulatus with Nitric Oxide Production Inhibition and Antimicrobial Activity.

Phytochemical study on the methanol extract of the leaves of Phyllanthus reticulatus led to the isolation of two new compounds, phyllanreticosides A (1) and B (2) together with ten known ones (3-12). Their chemical structures were determined by HR-ESI-MS, NMR, and ECD spectra in comparison with the literature. Three ellagitannins, phyllanreticoside A (1), corilagin (3), and phyllanthusiin C (4) inhibited lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values of 63.2, 83.2, and 5.6 µM, respectively. In addition, compounds 1, 3, and 4 exhibited significantly antimicrobial activity (MICs: 16-128 µg/mL) towards some of seven microbial strains, including Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Candida albicans.

Bioactive prenylated c6–c3 derivatives from the roots of Illicium brevistylum

Three new prenylated C6–C3 compounds (1–3), together with two known prenylated C6–C3 compounds (4–5) and one known C6–C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1–3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 μM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4–6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 μM.

Inhibition of nitric oxide production in RAW 264.7 cells and cytokines IL-1β in osteoarthritis rat models of 70 % ethanol extract of Arcangelisia flava (L.) merr stems

IntroductionOne of the most frequent types of arthritis is osteoarthritis, also referred to as a degenerative joint disease. Interleukin-1β (IL-1β) and nitric oxide (NO) are essential factors in the pain response; IL-1β and NO are responsible for increasing the production of matrix metalloproteinases (MMP) and a disintegrin-like and metalloproteinases with thrombospondin motifs (ADAMS) in chondrocytes. Arcangelisia flava (L.) Merr. Has been traditionally used to treat jaundice, liver disease, diarrhea, fever, and inflammation. MethodsThis study used in vitro and in vivo models to determine the effect of a 70 % ethanol extract of Arcangelisia flava (L.) Merr. stems on the inhibition of NO production in RAW 264.7 cells induced with lipopolysaccharide (LPS) and IL-1β in osteoarthritis rats induced with monosodium iodoacetate (MIA). The NO inhibition test was determined by the NO colorimetric assay using Griess reagent and measured by the ELISA plate reader. The measurement of joint diameter and hyperalgesia in osteoarthritis rats was carried out once a week for 7 weeks, and then the IL-1β levels were measured at weeks 3 and 7. ResultThe viability of cell line this extract was greater than 80 %, and the extract at 25, 50, and 100 μg/mL significantly inhibited NO production (p < 0.0001) in RAW 264.7 cells induced with LPS. Meanwhile, this extract at 10, 30, and 90 mg/200g BW increased latency time, reduced joint swelling, and reduced IL-1β levels in the serum in the osteoarthritis rat model. Conclusion70 % ethanol extract of Arcangelisia flava (L.) Merr. Has the potential to be an anti-osteoarthritis drug.

Superabsorbent crosslinked carboxymethyl cellulose-PEG hydrogel containing a nutgall extract as a broad antimicrobial agent for wound dressing applications

The treatment of chronic wounds encounters major challenges from oxidative stress that results from chronic inflammation and microbial infections. A hydrogel containing an ethanolic extract of Quercus infectoria galls (Qi) was developed as a new therapeutic strategy for the treatment of chronically infected wounds. FTIR confirmed the presence of bioactive compounds with 9.42 mg/g gallic acid as revealed by HPLC. Qi hydrogel presented a rough and compact surface with macroporous networks that contributed to an extremely high absorption of wound exudate equivalent to approximately 2300 % of the weight of the hydrogel. The biological activities of Qi hydrogel were compared with those of commercially-available products. According to the kinetic release, the correlation coefficients showed that the hydrogel fitted to the Higuchi model. Qi hydrogel exhibited strong antimicrobial activity against pathogens of clinical importance associated with wound infections. Minimum inhibitory concentrations and minimum bactericidal/fungicidal concentrations ranged from 0.24 to 250 and 3.91 to >250 mg/mL, respectively. In addition, microbial biofilms were significantly inhibited compared with the untreated control (p < 0.05). At concentrations from 0.78 to 12.5 mg/mL, Qi hydrogel scavenged almost 100 % of DPPH and ABTS radicals and showed a ferric ion reducing power of 443.11 μM FeSO4/g hydrogel by FRAP assay. A biocompatibility assessment of the hydrogel on L929 fibroblast cells confirmed no toxic effects and the hydrogel significantly inhibited lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages (p < 0.05). The absorbency, permeability, phytochemical compounds and biological activities of Qi hydrogel are suitable properties of a dressing for treating and preventing chronically infected wounds.

Structurally diverse diterpenoids from the seeds of Caesalpinia minax Hance and their bioactivities

Eight previously undescribed diterpenoids, caesamins A–H (1–8), were separated and identified from the seeds of Caesalpinia minax Hance. Their structures were characterized by extensive spectroscopic data and X-ray crystallographic analysis. Structurally, caesamin A (1) is the first cassane-type diterpenoid with a C23 carbon skeleton containing an unusual isopropyl. Caesamin F (6) represents the first example of cleistanthane diterpenoid from the genus Caesalpinia. Caesamins B (2) and F (6) exhibited inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 45.67 ± 0.92 and 42.99 ± 0.24 μM, comparable to positive control 43.69 ± 2.62 μM of NG-Monomethyl-L-arginine. Furthermore, the chemotaxonomic significance of the isolates was discussed.

Essential Oil from Vietnamese Peperomia leptostachya Hook. & Arn. (Piperaceae): Chemical Composition, Antioxidant, Anti-Inflammatory, Cytotoxic Activities, and In Silico Analysis.

This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and β-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 μg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.

Revealing the anti-inflammatory activity of Euphorbia hirta extract: transcriptomic and nitric oxide production analysis in LPS-Induced RAW 264.7 cells

ABSTRACT Excessive production of nitric oxide (NO) dan pro-inflammatory cytokines can lead to tissue damage and chronic inflammation. Euphorbia hirta presents an interesting opportunity for plant-derived anti-inflammatory agents as it contains a range of compounds which have demonstrated anti-inflammatory effects. This study investigates the anti-inflammatory properties of E. hirta extract on gene expression and NO production in LPS-treated RAW 264.7 cells. The results demonstrate that E. hirta extracts effectively suppress NO production in RAW 264.7 cells. Furthermore, the extract inhibits iNOS protein expression and reduces the expression of pro-inflammatory cytokines TNF-α and IL−12. RNA sequencing revealed significant alterations in gene expression, including 167 upregulated and 56 downregulated genes-related inflammation pathways. The study concludes that E. hirta extract possesses anti-inflammatory activity by modulating gene expression and inhibiting NO production in LPS-treated RAW 264.7 cells. The extract influences genes associated with inflammation signalling pathways, including cytokine signalling, NF-κB, iNOS and JAK-STAT pathways.

New alkaloids from Stemona tuberosa and structural revision of tuberostemonols P and R

Three Stemona alkaloids named stemotuberines A–C (1–3) with unique C17N frameworks, presumably formed by elimination of the C-11–C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC50 values of 37.1 and 23.2 μM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O–R (4–7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1H and 13C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a.

Enhancing the nitric oxide inhibitory activity using a combination of plant essential oils and mixture design approach

The synergistic effects of essential oils (EOs) from three aromatic plant species, Foeniculum vulgare subsp. piperitum (C.Presl) Bég. (FV), Origanum heracleoticum L. (OH) and Lavandula austroapennina N.G.Passal., Tundis & Upson. (LA), were evaluated for their inhibitory properties on nitric oxide production in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). We utilized a Design of Experiments (DoE) methodology to optimize a formulation by combining three Essential Oils (EOs), while simultaneously taking into account two response variables, maximization of NO inhibition with minimum cytotoxicity. The optimal blend of components was predicted, and the statistical outcome's efficacy was experimentally verified. The combination corresponding to 87.7 % FV, 12.3 % LA and 0.0 % OH showed high inhibitory effect (76.3 %) with negligible cytotoxicity (4.5 %). This research provides new information on the interactions among fennel, oregano and lavender essential oils and shows how they can synergistically inhibit in vitro LPS-induced NO production.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells.

Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.

Comparison of immunomodulatory activity of polysaccharides and soluble dietary fibers and adsorption capacities of insoluble dietary fibers extracted from Lentinus edodes stipes

Stipes are the major waste from the processing of Lentinus edodes. To make full use of L. edodes stipes (LES), different fractions of LES polysaccharides (LESPs) were first obtained by water extraction and gradient ethanol precipitation. Afterwards, the LES residues were treated with an optimal combination of Aspergillus niger and Saccharomyces cerevisiae for the preparation of soluble/insoluble dietary fibers (LESS/LESI) using the response surface methodology and the Box-Behnken design. Subsequently, the in vitro immunomodulatory activity of LESPs and LESS, as well as the adsorption capacities of LESI were evaluated. The results showed that LESPs were neutral polysaccharides, mainly containing glucose. The optimal parameters for modifying the residues of LES were the followings: 4% (w/w) A. niger, 8% (w/w) S. cerevisiae, 31 ℃, 3 d, and a solid–liquid ratio of 1:12.5 in a yield of 14.73%/82.45% of LESS/LESI, respectively. The in vitro immunomodulatory activity assays revealed that LESPs and LESS had potent immunostimulatory activity to increase phagocytosis, acid phosphatase activity and nitric oxide production of RAW264.7 murine cell macrophages. The evaluation of adsorption capacities revealed that LESI owned stronger water holding capacity, oil holding capacity and water swelling capacity. This research could provide an effective way to fully utilize discarded L. edodes stipes with high added-value.Graphical An effective strategy was built to fully utilize discarded L. edodes stipes by preparing polysaccharides (LESPs-20, LESPs-50 and LESPs-80), soluble and insoluble dietary fibers (LESS/LESI). Their products showed immunomodulatory activity and adsorption capacities.

Isolation and characterization of dihydrohomoisoflavonoids from Portulaca oleracea L.

Eight pairs of dihydrohomoisoflavonoids (1−8), including four pairs of enantiomeric aglycones [(R,S)-portulacanones B (1) and C (2) and (R,S)-oleracones C (3) and Q (4)] and four pairs of epimeric glycosides [portulacasides A−D and epiportulacasides A−D (5−8)], were obtained from Portulaca oleracea L. Among them, (R,S)-oleracone Q (4) and four pairs of epimeric glycosides (5−8) were reported for the first time. The 50% EtOH fraction from the 70% EtOH extract prevented HepG2 human liver cancer cell damage induced by N-acetyl-p-aminophenol (APAP), and the cell survival rate was 62.3%. Portulacaside B (6a), which was isolated from the 50% EtOH fraction, exhibited hepatoprotective and anti-inflammatory effects. The compound increased the survival rate of APAP-damaged HepG2 human liver cancer cells from 40.0% to 51.2% and reduced nitric oxide production in RAW 264.7 macrophages, resulting in an inhibitory rate of 46.8%.

Antioxidant, anti-inflammatory, and antibacterial activities against acne-causing bacteria of Miliusa velutina (A.DC.) Hook.f. &amp; Thomson extracts

Context: Acne is often associated with bacterial infection, inflammation, and oxidative stress. In Thailand, Miliusa velutina has traditionally been used to relieve pain and to heal wounds. Given its biological properties, M. velutina extracts may represent an alternative approach to treat acne. Aims: To characterise M. velutina extracts regarding their antioxidant and anti-inflammatory properties and antibacterial activity against acne-causing bacteria. Methods: We prepared crude methanolic and aqueous extracts of M. velutina leaves and stem bark by maceration. We evaluated the antioxidant activity of the extracts by using four in vitro methods and determined the total phenolic and flavonoid contents. We tested the anti-inflammatory activity of the extracts by examining their ability to inhibit nitric oxide production in RAW 264.7 macrophages. We tested the antibacterial activity against acne-causing bacteria by using the agar diffusion method and by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Results: The methanolic bark extract showed potent antioxidant properties, denoted by its ability to scavenge the ABTS and DPPH radicals and its iron-reducing power and total antioxidant activity. The methanolic leaf extract presented the best ability to inhibit nitric oxide production, with a half maximal inhibitory concentration (IC50) of 7.20 ± 1.92 µg/mL. Additionally, M. velutina extracts exhibited antibacterial activity against Cutibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, methicillin-resistant S. aureus and Pseudomonas aeruginosa, with the MIC and MBC ranging from 0.49 to 62.50 mg/mL. Conclusions: These findings indicate that M. velutina extract can be used as a novel therapeutic agent for acne treatment owing to its antioxidant, anti-inflammatory and antibacterial properties.

HPPO-Derived Meroterpenoids from the Marine-Derived Fungus Penicillium sp. SCSIO 41691.

Seven new 4-hydroxy-6-phenyl-2H-pyran-2-one (HPPO) derived meroterpenoids, 1-methyl-12a,12b-epoxyarisugacin M (1), 1-methyl-4a,12b-epoxyarisugacin M (2), 2,3-dihydroxy-3,4a-epoxy-12a-dehydroxyisoterreulactone A (3), 2-hydroxy-12a-dehydroxyisoterreulactone A (4), 3'-demethoxyterritrems B' (5), 4a-hydroxyarisugacin P (6), and 1-epi-arisugacin H (7), together with two known analogues (8 and 9), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41691. Their structures were elucidated by spectroscopic methods, and the absolute configurations of compounds 1 and 3 were determined by single-crystal X-ray diffraction. Among them, 1 and 2 had a unique methyl migration in the basic meroterpenoid skeleton with a 12a,12b-epoxy or 4a,12b-epoxy group, and 3 was a highly oxygenated HPPO-derived meroterpenoid featuring a rare 6/5/6/6/6/6 hexacyclic system with a 3,4a-epoxy group. Biologically, 5 exhibited inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 21 μM, more potent than the positive control indomethacin.

Anti-inflammatory monoterpenes from morinda (Morinda officinalis How.)

Morinda (Morinda officinalis How.) is widely consumed as a functional food owing to its potential to promote health. This study investigated the anti-inflammatory phytochemicals of morinda and isolated 30 monoterpenes, including 6 undescribed iridoids (1, 6, 9–11 and 25), 2 undescribed acyclic monoterpenoids (28, 29), a known acyclic monoterpenoid and 21 known iridoids. Their chemical and stereo-structures were elucidated based on HR–ESI–MS, NMR, 13C-NMR calculations, ECD data and ECD calculations. Notably, compounds 11, 12 and 20 exerted pronounced inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values of 28.51 ± 1.70, 25.45 ± 4.17 and 29.17 ± 3.71 μM respectively (indomethacin, IC50 of 33.68 ± 2.19 μM). The same compounds exert anti-inflammatory effects by blocking nuclear translocation of nuclear factor κ-B, and down-regulating the expression of inflammatory cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1β and interleukin-6 at mRNA and protein levels in a dose-dependent manner. These results suggest that moderate consumption of morinda helps prevent and reduce the occurrence of inflammatory-related diseases.

Metabolites Profile of Extracts and Fractions of Erythroxylum mexicanum Kunth by UHPLC-QTOF-MS/MS and its Antibacterial, Cytotoxic and Nitric Oxide Inhibitory Activities.

The present study shows the untargeted metabolite profiling and in vitro antibacterial, cytotoxic, and nitric oxide (NO) inhibitory activities of the methanolic leaves extract (MLE) and methanolic stem extract (MSE) of Erythroxylum mexicanum, as well as the fractions from MSE. Using ultra-high performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS), a total of 70 metabolites were identified; mainly alkaloids in the MLE, while the MSE showed a high abundance of diterpenoids. The MSE fractions exhibited differential activity against Gram-positive bacteria. Notably, the hexane fraction (HSF) against Streptococcus pyogenes ATCC 19615 (MIC=62.5 μg/mL) exhibited a bactericidal effect. The MSE fractions exhibited cytotoxicity against all cancer cell lines tested, with selectivity towards them compared to a noncancerous cell line. Particularly, the HSF and chloroform fraction (CSF) showed the highest cytotoxicity against prostate cancer (PC-3) cells, with IC50 values of 19.9 and 18.1 μg/mL and selectivity indexes of 3.8 and 4.2, respectively. Both the HSF and ethyl acetate (EASF) fractions of the MSE inhibited NO production in RAW 264.7 macrophages, with NO production percentages of 50.0 % and 51.7 %, respectively, at a concentration of 30 μg/mL. These results indicated that E. mexicanum can be a source of antibacterial, cytotoxic, and anti-inflammatory metabolites.

New diterpene lactone derivatives from Aphanamixis polystachya leaves inhibit nitric oxide production in RAW 264.7 cells.

Phytochemical studies on Aphanamixis plants have attracted considerable attention over the past few decades due to the structural diversities and significant biological activities of terpenoids produced by these plants. In the present study, five new acyclic diterpene lactone derivatives, aphanamixionolides A-E (1-5), and three known tirucallane-type triterpenes, namely, piscidinol A (6), hispidone (7), and bourjotinolone A (8), were isolated from the leaves of Aphanamixis polystachya. Their structures were elucidated by comprehensive analyses of HR-ESI-MS and NMR spectroscopic data and by comparison with those reported in the literature. Absolute configurations of the new compounds were determined by experimental and TD-DFT calculated ECD spectra. Compounds 1-8 inhibited NO production with IC50 values of 10.2-37.7 μM, which are comparable to positive control l-NMMA (IC50: 31.5 μM).