Bioactive Phytochemicals from Mulberry: Potential Anti-Inflammatory Effects in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

The fruits of the mulberry tree (Morus alba L.), known as white mulberry, have been consumed in various forms, including tea, beverages, and desserts, worldwide. As part of an ongoing study to discover bioactive compounds from M. alba fruits, the anti-inflammatory effect of compounds from M. alba were evaluated in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages. Phytochemical analysis of the ethanol extract of the M. alba fruits led to the isolation of 22 compounds. Among the isolated compounds, to the best of our knowledge, compounds 1, 3, 5, 7, 11, 12, and 14–22 were identified from M. alba fruits for the first time in this study. Inhibitory effects of 22 compounds on the production of the nitric oxide (NO) known as a proinflammatory mediator in LPS-stimulated RAW 264.7 macrophages were evaluated using NO assays. Western blot analysis was performed to evaluate the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5). We evaluated whether the anti-inflammatory effects of cyclo(L-Pro-L-Val) (5) following LPS stimulation in RAW 264.7 macrophages occurred because of phosphorylation of IκB kinase alpha (IKKα), IκB kinase beta (IKKβ), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB) and activations of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Cyclo(L-Pro-L-Val) (5) significantly suppressed phosphorylations of IKKα, IKKβ, IκBα, and NF-κB and activations of iNOS and COX-2 in a concentration-dependent manner. Taken together, these results indicate that cyclo(L-Pro-L-Val) (5) can be considered a potential therapeutic agent for the treatment of inflammation-associated disorders.     

Secondary Metabolic Profile as a Tool for Distinction and Characterization of Cultivars of Black Pepper (Piper nigrum L.) Cultivated in Pará State,Brazil

This study evaluated the chemical compositions of the leaves and fruits of eight black pepper cultivars cultivated in Pará State (Amazon, Brazil). Hydrodistillation and gas chromatography–mass spectrometry were employed to extract and analyze the volatile compounds, respectively. Sesquiterpene hydrocarbons were predominant (58.5–90.9%) in the cultivars “Cingapura”, “Equador”, “Guajarina”, “Iaçará”, and “Kottanadan”, and “Bragantina”, “Clonada”, and “Uthirankota” displayed oxygenated sesquiterpenoids (50.6–75.0%). The multivariate statistical analysis applied using volatile composition grouped the samples into four groups: γ-Elemene, curzerene, and δ-elemene (“Equador”/“Guajarina”, I); δ-elemene (“Iaçará”/“Kottanadan”/“Cingapura”, II); elemol (“Clonada”/“Uthirankota”, III) and α-muurolol, bicyclogermacrene, and cubebol (“Bragantina”, IV). The major compounds in all fruit samples were monoterpene hydrocarbons such as α-pinene, β-pinene, and limonene. Among the cultivar leaves, phenolics content (44.75–140.53 mg GAE·g⁻¹ FW), the enzymatic activity of phenylalanine-ammonia lyase (20.19–57.22 µU·mL⁻¹), and carotenoids (0.21–2.31 µg·mL⁻¹) displayed significant variations. Due to black pepper’s susceptibility to Fusarium infection, a molecular docking analysis was carried out on Fusarium protein targets using each cultivar’s volatile components. F. oxysporum endoglucanase was identified as the preferential protein target of the compounds. These results can be used to identify chemical markers related to the susceptibility degree of black pepper cultivars to plant diseases prevalent in Pará State.     

Effect of Neprilysin Inhibition for Ischemic Mitral Regurgitation after Myocardial Injury

Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL; p < 0.05), while valsartan did not (471.2 ± 8.9 µL; p > 0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm; p < 0.05). Transforming growth factor-β and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.     

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB₁), type two (CB₂), and the G protein-coupled receptor 55 (GPR₅₅)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.     

Antioxidant Systems from Pepper (Capsicum annuum L.): Involvement in the Response to Temperature Changes in Ripe Fruits

Sweet pepper is susceptible to changes in the environmental conditions, especially temperatures below 15 °C. In this work, two sets of pepper fruits (Capsicum annuum L.) which underwent distinct temperature profiles in planta were investigated. Accordingly, two harvesting times corresponding to each set were established: Harvest 1, whose fruits developed and ripened at 14.9 °C as average temperature; and Harvest 2, with average temperature of 12.4 °C. The oxidative metabolism was analyzed in all fruits. Although total ascorbate content did not vary between Harvests, a shift from the reduced to the oxidized form (dehydroascorbate), accompanied by a higher ascorbate peroxidase activity, was observed in Harvest 2 with respect to Harvest 1. Moreover, a decrease of the ascorbate-generating enzymatic system, the γ-galactono-lactone dehydrogenase, was found at Harvest 2. The activity values of the NADP-dependent dehydrogenases analyzed seem to indicate that a lower NADPH synthesis may occur in fruits which underwent lower temperature conditions. In spite of the important changes observed in the oxidative metabolism in fruits subjected to lower temperature, no oxidative stress appears to occur, as indicated by the lipid peroxidation and protein oxidation profiles. Thus, the antioxidative systems of pepper fruits seem to be involved in the response against temperature changes.     

Natural Bioactive Compounds from Winery By-Products as Health Promoters: A Review

The relevance of food composition for human health has increased consumers’ interest in the consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals. This fact has led to a growing attention of suppliers on reuse of agro-industrial wastes rich in healthy plant ingredients. On this matter, grape has been pointed out as a rich source of bioactive compounds. Currently, up to 210 million tons of grapes (Vitis vinifera L.) are produced annually, being the 15% of the produced grapes addressed to the wine-making industry. This socio-economic activity generates a large amount of solid waste (up to 30%, w/w of the material used). Winery wastes include biodegradable solids namely stems, skins, and seeds. Bioactive compounds from winery by-products have disclosed interesting health promoting activities both in vitro and in vivo. This is a comprehensive review on the phytochemicals present in winery by-products, extraction techniques, industrial uses, and biological activities demonstrated by their bioactive compounds concerning potential for human health.     

In Vitro Activity of Copper(II) Complexes,Loaded or Unloaded into a Nanostructured Lipid System,against Mycobacterium tuberculosis

Tuberculosis (TB) is an infectious disease caused mainly by the bacillus Mycobacterium tuberculosis (Mtb), presenting 9.5 million new cases and 1.5 million deaths in 2014. The aim of this study was to evaluate a nanostructured lipid system (NLS) composed of 10% phase oil (cholesterol), 10% surfactant (soy phosphatidylcholine, sodium oleate), and Eumulgin^® HRE 40 ([castor oil polyoxyl-40-hydrogenated] in a proportion of 3:6:8), and an 80% aqueous phase (phosphate buffer pH = 7.4) as a tactic to enhance the in vitro anti-Mtb activity of the copper(II) complexes [CuCl₂(INH)₂]·H₂O (1), [Cu(NCS)₂(INH)₂]·5H₂O (2) and [Cu(NCO)₂(INH)₂]·4H₂O (3). The Cu(II) complex-loaded NLS displayed sizes ranging from 169.5 ± 0.7095 to 211.1 ± 0.8963 nm, polydispersity index (PDI) varying from 0.135 ± 0.0130 to 0.236 ± 0.00100, and zeta potential ranging from −0.00690 ± 0.0896 to −8.43 ± 1.63 mV. Rheological analysis showed that the formulations behave as non-Newtonian fluids of the pseudoplastic and viscoelastic type. Antimycobacterial activities of the free complexes and NLS-loaded complexes against Mtb H₃₇Rv ATCC 27294 were evaluated by the REMA methodology, and the selectivity index (SI) was calculated using the cytotoxicity index (IC₅₀) against Vero (ATCC^® CCL-81), J774A.1 (ATCC^® TIB-67), and MRC-5 (ATCC^® CCL-171) cell lines. The data suggest that the incorporation of the complexes into NLS improved the inhibitory action against Mtb by 52-, 27-, and 4.7-fold and the SI values by 173-, 43-, and 7-fold for the compounds 1, 2 and 3, respectively. The incorporation of the complexes 1, 2 and 3 into the NLS also resulted in a significant decrease of toxicity towards an alternative model (Artemia salina L.). These findings suggest that the NLS may be considered as a platform for incorporation of metallic complexes aimed at the treatment of TB.     

Supercritical Carbon Dioxide and Microwave-Assisted Extraction of Functional Lipophilic Compounds from Arthrospira platensis

Arthrospira platensis biomass was used in order to obtain functional lipophilic compounds through green extraction technologies such as supercritical carbon dioxide fluid extraction (SFE) and microwave-assisted extraction (MAE). The temperature (T) factor was evaluated for MAE, while for SFE, pressure (P), temperature (T), and co-solvent (ethanol) (CS) were evaluated. The maximum extraction yield of the obtained oleoresin was (4.07% ± 0.14%) and (4.27% ± 0.10%) for SFE and MAE, respectively. Extracts were characterized by gas chromatography mass spectrometry (GC-MS) and gas chromatography flame ionization detector (GC-FID). The maximum contents of functional lipophilic compounds in the SFE and MAE extracts were: for carotenoids 283 ± 0.10 μg/g and 629 ± 0.13 μg/g, respectively; for tocopherols 5.01 ± 0.05 μg/g and 2.46 ± 0.09 μg/g, respectively; and for fatty acids 34.76 ± 0.08 mg/g and 15.88 ± 0.06 mg/g, respectively. In conclusion, the SFE process at P 450 bar, T 60 °C and CS 53.33% of CO₂ produced the highest yield of tocopherols, carotenoids and fatty acids. The MAE process at 400 W and 50 °C gives the best extracts in terms of tocopherols and carotenoids. For yield and fatty acids, the MAE process at 400 W and 70 °C produced the highest values. Both SFE and MAE showed to be suitable green extraction technologies for obtaining functional lipophilic compounds from Arthrospira platensis.     

The Effect of Germination on Phenolic Compounds and Antioxidant Activity of Pulses

In this study the changes of phenolic compounds and antioxidant activity of four different pulses namely white bean (Phaseolus vulgaris L), Common vetch (Vicia sativa), Lentil (Lens culinaris) and Chickpea (Cicer arietinum) seeds before and after germination were investigated. Seeds germinated in dark chambers maintained near 100 % relative humidity at 20 °C. Three different solvents namely acetone, hexane and methanol were employed to extract the phenolic compounds present in the seeds and sprouts. Total content of phenolic compounds was measured by the Folin–Ciocalteu method and antioxidant activity determined by the delay in fat oxidation. Different concentrations of extracts (0.02 and 0.1 % w/w) were added to tallow and the stabilities of the treatments were determined by the peroxide value and induction period measurements to evaluate the antioxidant activities. The results indicated that the increases in phenolic content from dormant seed to sprouted seed were significant (P ≤ 0.05) in all the samples. The significant differences between induction periods of tallow treated with sprouted seed extracts were observed (P < 0.05). The results indicated that the greatest increase in stability was obtained when tallow was treated with a 0.1 % concentration of acetone chickpea sprout extract. The pulses' sprout flour or extract might be recommended for use as a source of natural antioxidants in functional foods.     

Collagen Family and Other Matrix Remodeling Proteins Identified by Bioinformatics Analysis as Hub Genes Involved in Gastric Cancer Progression and Prognosis

Gastric cancer has remained in the top five cancers for over ten years, both in terms of incidence and mortality due to the shortage of biomarkers for disease follow-up and effective therapies. Aiming to fill this gap, we performed a bioinformatics assessment on our data and two additional GEO microarray profiles, followed by a deep analysis of the 40 differentially expressed genes identified. PPI network analysis and MCODE plug-in pointed out nine upregulated hub genes coding for proteins from the collagen family (COL12A1, COL5A2, and COL10A1) or involved in the assembly (BGN) or degradation of collagens (CTHRC1), and also associated with cell adhesion (THBS2 and SPP1) and extracellular matrix degradation (FAP, SULF1). Those genes were highly upregulated at the mRNA and protein level, the increase being correlated with pathological T stages. The high expression of BGN (p = 8 × 10⁻¹²), THBS2 (p = 1.2 × 10⁻⁶), CTHRC1 (p = 1.1 × 10⁻⁴), SULF1 (p = 3.8 × 10⁻⁴), COL5A1 (p = 1.3 × 10⁻⁴), COL10A1 (p = 5.7 × 10⁻⁴), COL12A1 (p = 2 × 10⁻³) correlated with poor overall survival and an immune infiltrate based especially on immunosuppressive M2 macrophages (p-value range 4.82 × 10⁻⁷–1.63 × 10⁻¹³). Our results emphasize that these genes could be candidate biomarkers for GC progression and prognosis and new therapeutic targets.     

The Impact of Hanseniaspora vineae Fermentation and Ageing on Lees on the Terpenic Aromatic Profile of White Wines of the Albillo Variety

Hanseniaspora vineae is a non-Saccharomyces yeast that has a powerful impact on the sensory profile of wines. Its effect on the aromatic profile of non-aromatic grape varieties, such as Albillo Mayor (Vitis vinifera, L), during vinification is a useful biotechnology to improve sensory complexity. Fermentation in steel barrels using Hanseniaspora vineae and sequential inoculation with Saccharomyces cerevisiae have been used to study the formation of terpenes and cell lysis in the production of Albillo white wines. The GC-MS analysis profile shows a significant effect of H. vineae fermentation on the contents of terpenes (≈×3), mainly in linalool (>×3), β-citronellol (>×4), geraniol (>×2) and α-terpineol (≈×2). The contents of several polyoxygenated terpenes and some volatile phenols with a spicy aroma were increased during fermentation. In summary, Hanseniaspora vineae releases a large number of cell wall polysaccharides during fermentation that affect wine palatability and structure. Hanseniaspora vineae is a powerful bio-tool to enhance the fruitiness, floral notes and freshness in non-aromatic white varieties.     

Using Synchrotron Radiation-Based Infrared Microspectroscopy to Reveal Microchemical Structure Characterization: Frost Damaged Wheat vs. Normal Wheat

This study was conducted to compare: (1) protein chemical characteristics, including the amide I and II region, as well as protein secondary structure; and (2) carbohydrate internal structure and functional groups spectral intensities between the frost damaged wheat and normal wheat using synchrotron radiation-based Fourier transform infrared microspectroscopy (SR-FTIRM). Fingerprint regions of specific interest in our study involved protein and carbohydrate functional group band assignments, including protein amide I and II (ca. 1774–1475 cm⁻¹), structural carbohydrates (SCHO, ca. 1498–1176 cm⁻¹), cellulosic compounds (CELC, ca. 1295–1176 cm⁻¹), total carbohydrates (CHO, ca. 1191–906 cm⁻¹) and non-structural carbohydrates (NSCHO, ca. 954–809 cm⁻¹). The results showed that frost did cause variations in spectral profiles in wheat grains. Compared with healthy wheat grains, frost damaged wheat had significantly lower (p < 0.05) spectral intensities in height and area ratios of amide I to II and almost all the spectral parameters of carbohydrate-related functional groups, including SCHO, CHO and NSCHO. Furthermore, the height ratio of protein amide I to the third peak of CHO and the area ratios of protein amide (amide I + II) to carbohydrate compounds (CHO and SCHO) were also changed (p < 0.05) in damaged wheat grains. It was concluded that the SR-FTIR microspectroscopic technique was able to examine inherent molecular structure features at an ultra-spatial resolution (10 × 10 μm) between different wheat grains samples. The structural characterization of wheat was influenced by climate conditions, such as frost damage, and these structural variations might be a major reason for the decreases in nutritive values, nutrients availability and milling and baking quality in wheat grains.     

Synthesis and Characterization of Some New Bis-Pyrazolyl-Thiazoles Incorporating the Thiophene Moiety as Potent Anti-Tumor Agents

A new series of 1,4-bis(1-(5-(aryldiazenyl)thiazol-2-yl)-5-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-3-yl)benzenes 3a–i were synthesized via reaction of 5,5′-(1,4-phenylene)bis(3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide) (1) with hydrazonoyl halides 2a–i. In addition, reaction of 1 with ethyl chloroacetate afforded bis-thiazolone derivative 8 as the end product. Reaction of compound 8 with methyl glyoxalate gave bis-thiazolone derivative 10. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. All the synthesized compounds were evaluated for their anti-tumor activities against hepatocellular carcinoma (HepG2) cell lines, and the results revealed promising activities of compounds 3g, 5e, 3e, 10, 5f, 3i, and 3f with IC₅₀ equal 1.37 ± 0.15, 1.41 ± 0.17, 1.62 ± 0.20, 1.86 ± 0.20, 1.93 ± 0.08, 2.03 ± 0.25, and 2.09 ± 0.19 μM, respectively.     

Metabolite Profiling of Manilkara zapota L. Leaves by High-Resolution Mass Spectrometry Coupled with ESI and APCI and In Vitro Antioxidant Activity, α-Glucosidase,and Elastase Inhibition Assays

High-resolution mass spectrometry equipped with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources was used to enhance the characterization of phytochemicals of ethanol extracts of Manilkara zapota L. leaves (ZLE). Sugar compounds, dicarboxylic acids, compounds of phenolic acids and flavonoids groups, and other phytochemicals were detected from the leaves. Antioxidant activity and inhibition potentiality of ZLE against α-glucosidase enzyme, and elastase enzyme activities were evaluated in in vitro analysis. ZLE significantly inhibited activities of α-glucosidase enzyme at a lower concentration (IC₅₀ 2.51 ± 0.15 µg/mL). Glucose uptake in C2C12 cells was significantly enhanced by 42.13 ± 0.15% following the treatment with ZLE at 30 µg/mL. It also exhibited potential antioxidant activities and elastase enzyme inhibition activity (IC₅₀ 27.51 ± 1.70 µg/mL). Atmospheric pressure chemical ionization mass spectrometry (APCI–MS) detected more m/z peaks than electrospray ionization mass spectrometry (ESI–MS), and both ionization techniques illustrated the biological activities of the detected compounds more thoroughly compared to single-mode analysis. Our findings suggest that APCI along with ESI is a potential ionization technique for metabolite profiling, and ZLE has the potential in managing diabetes by inhibiting α-glucosidase activity and enhancing glucose uptake.     

New Coumarin Derivatives and Other Constituents from the Stem Bark of Zanthoxylum avicennae: Effects on Neutrophil Pro-Inflammatory Responses

Three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2), and (Z)-avicennone (3), have been isolated from the stem bark of Zanthoxylum avicennae (Z. avicennae), together with 15 known compounds (4–18). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4, 9, 12, and 15 exhibited inhibition (half maximal inhibitory concentration (IC₅₀) values ≤7.65 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, 4, 8 and 9 inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤8.17 µg/mL. This investigation reveals bioactive isolates (especially 1, 2, 4, 8, 9, 12 and 15) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.     

Serum Selenium and Ceruloplasmin in Nigerians with Peripartum Cardiomyopathy

The study aimed to determine if selenium deficiency, serum ceruloplasmin and traditional birth practices are risk factors for peripartum cardiomyopathy (PPCM), in Kano, Nigeria. This is a case-control study carried out in three hospitals, and PPCM patients were followed up for six months. Critically low serum selenium concentration was defined as <70 µg/L. A total of 39 PPCM patients and 50 controls were consecutively recruited after satisfying the inclusion criteria. Mean serum selenium in patients (61.7 ± 14.9 µg/L) was significantly lower than in controls (118.4 ± 45.6 µg/L) (p < 0.001). The prevalence of serum selenium <70 µg/L was significantly higher among patients (76.9%) than controls (22.0%) (p < 0.001). The mean ceruloplasmin and prevalence of socio-economic indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy were not different between the groups (p > 0.05). Logistic regression showed that rural residency significantly increased the odds for serum selenium <70 µg/L by 2.773-fold (p = 0.037). Baseline serum levels of selenium and ceruloplasmin were not associated with six-month mortality. This study has shown that selenium deficiency is a risk factor for PPCM in Kano, Nigeria, and is related to rural residency. However, serum ceruloplasmin, customary birth practices and some other characteristics were not associated with PPCM in the study area.     

New Coumarins and Anti-Inflammatory Constituents from the Fruits of Cnidium monnieri

The fruit of Cnidium monnieri is commercially used as healthcare products for the improvement of impotence and skin diseases. Three new coumarins, 3''-O-methylmurraol (1), rel-(1''S,2''S)-1''-O-methylphlojodicarpin (2), and (1''S,2''S)-1''-O-methylvaginol (3), have been isolated from the fruits of C. monnieri, together with 14 known compounds (4–17). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4–12, and 14–17 exhibited inhibition (IC₅₀ ≤ 7.31 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 7, 9–11, 15, and 17 inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤7.83 µg/mL. This investigation reveals that bioactive isolates (especially 6, 7, 14, and 17) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.