Anti-inflammatory Activity Of Compounds Research Articles

Anti-inflammatory Activities and Mechanisms of New Compounds Isolated from the Fruits of Foeniculum vulgare Mill.

Forty-nine compounds, including six previously unknown together with forty-three known ones, were isolated from the fruits of Foeniculum vulgare Mill. Their structures were elucidated using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), infrared spectroscopy (IR), ultraviolet-visible spectroscopy (UV), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) methods. All isolates were evaluated their anti-inflammatory activity. The results indicated that compounds 1, 6, 35 and 45 inhibit lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 17.13 ± 0.74, 14.40 ± 0.54, 112.13 ± 2.08 and 77.02 ± 3.62 μg/mL, respectively. Moreover, the potential targets of the four active ingredients were explored through network pharmacology, revealing that SRC, TP53, AKT1, and PIK3CA may serve as key anti-inflammatory targets. To confirm the potential binding mode, molecular docking was employed, which demonstrated that all active targets except SRC exhibited favorable binding energy with compound 35. Additionally, the anti-inflammatory activities of compounds 1-6 were first observed in this experiment.

Three Undescribed Protoilludane-Type Sesquiterpene Aryl Esters from Armillaria gallica.

Three previously undescribed protoilludane-type sesquiterpene aryl esters, armillanals A-C (1-3), along with seven known ones (4-10) were obtained from Armillaria gallica Marxm. & Romagn. Compounds 1 and 2 were a rare class of sesquiterpenes featuring the Δ2(3) and Δ12(13)-protoilludane skeleton. Their structures were established by extensive spectroscopic methods. Based on electronic circular dichroism (ECD) calculations, the absolute configurations of three new compounds (1-3) were determined. The anti-inflammatory activity of compounds 1-10 was screened and compound 3 could dose-dependently decrease the level of lactate dehydrogenase, showing IC50 value of 4.525 μM.

Three new chemical constituents of Senecio raphanifolius

Three new constituents, 4a-hydroxy-1-methyl-4,4a,8,8a-tetrahydro-1 H-isochromene-3,7-dione (1), 1-(2-(prop-1-en-2-yl)-3-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2 H-pyran-2-yl)oxy)-2,3-dihydrobenzofuran-5-yl)ethan-1-one (2), and 5-(hydroxymethyl)-2,3-dihydro-1 H-pyrrolizin-1-one (3), together with 3 known flavonoids (4-6), 6 organic acids (7-12), 1 glycoside (13), and 2 terpenoids (14-15) were isolated from the 50 % ethanol extract of the whole plant of Senecio raphanifolius Wall. ex DC. The structures of these novel compounds were determined using high-resolution electrospray ionization–mass spectrometry and NMR, mainly using 2D NMR. The anti-inflammatory activities of compounds 1-3 were evaluated based on their ability to inhibit nitric oxide (NO) production in lipopolysaccharide-stimulated RAW264.7 cells. Compound 1 could reduce NO levels and had an inhibition rate of 42.86 % at 100 µM.

Clypeasterol, a novel aromatic ergosterol skeleton from the mushroom Entoloma clypeatum

Chemical investigation of the wild mushroom Entoloma clypeatum led to the isolation of one new A-nor B-aromatic C28 steroid (1), along with eight known compounds (2–9) from this mushroom. As far as we know, compound 1 represents an unprecedented type of natural product. The structure of the new compound was elucidated based on extensive spectroscopic data analysis of HR-ESI-MS, 1D, and 2D NMR, while the relative configuration was confirmed by NOESY correlations. In addition, the anti-inflammatory activity of compound 1 was evaluated against LPS induced NO production in RAW 264.7 macrophages. Compound 1 exhibited a moderate anti-inflammatory activity with an IC50 value of 24.56 ± 1.72 μM.

Study on anti-inflammatory activity of phenolic acids from Leucas ciliata

The chemical constituents from Leucas ciliata belonging to Leucas genus in Lamiaceae were systematically explored by silica gel column chromatography, ODS column chromatography, Sephadex LH-20 gel column chromatography, and preparative high performance liquid chromatography, and seventeen phenolic acids were isolated. The chemical structures of the compounds were identified by their physicochemical properties, spectroscopic data, and literature. They were 4-hydroxyphenethyl ethyl succinate(1), 4-hydroxyphenethyl methyl succinate(2), 2-(4-hydroxyphenyl) ethyl acetate(3), p-hydroxyphenylethyl anisate(4), cassia cis-trans diphenylpropanoid(5), p-coumaric acid(6), 3,4-dihydroxybenzenepropionic acid methyl ester(7), caffeic acid(8), trans-p-hydroxyl ethyl cinnamate(9), methyl p-hydroxybenzeneacetate(10), 4-hydroxyphenethyl alcohol(11), syringic acid(12), vanillin(13), protocatechuic acid(14), salicylic acid(15), p-hydroxybenzaldehyde(16), and diorcinol(17). Among them, compound 1 was new, and compounds 2-10, 12, 14, and 16-17 were isolated from the plants belonging to Leucas genus for the first time. All compounds were obtained from L. ciliata for the first time. The anti-inflammatory activity of compounds 1-17 on NO production in lipopolysaccharide(LPS)-induced mouse leukemia cells of monocyte macrophage(RAW264. 7) cells was evaluated. The results showed that compounds 5, 7, and 9 exhibited significant anti-inflammatory activity, with IC50values of(10. 14±0. 36)-(21. 17±0. 11) μmol·L~(-1).

Isolation, characterization and anti-inflammatory activity of compounds from the Vernonia amygdalina

The need to explore the abundance of natural products cannot be overemphasized particularly in the management of various disease conditions. In traditional medical practice, Vernonia amygdalina has been widely adopted in the management of various inflammatory disorders. The objective of this investigation was to isolate the bioactive principles from the stem-bark and root of V. amygdalina and assess the anti-inflammatory (in vitro) activity of both the crude extracts and the isolated compounds. Following extraction with the methanol, the extract was subjected to gravity column chromatography and the resultant fractions was further purified to obtained pure compounds. The structural elucidation of the compounds were based on data obtained from 1H to 13C nuclear magnetic resonance (NMR) spectroscopies as well as fourier transform infrared (FT-IR). Using diclofenac as a control drug, the albumin denaturation assay was used to determine the in vitro anti-inflammatory activity of the extracts and isolates. Three distinct compounds characterized are vernoamyoside D, luteolin-7-α-o-glucuronide, and vernotolaside, a new glycoside. When compared to diclofenac, which has an IC50 of 167.8 μg/mL, luteolin-7-α-o-glucuronide, vernoamyoside D, and vernotolaside all showed significant inhibitions with respective IC50 values 549.8, 379.5, and 201.7 μg/mL. Vernotolaside is reported for the first time from the root. The assertion that the plant is used in traditional medicine for the management of inflammatory disorder is somewhat validated by the confirmation of the existence of the compounds with the biochemical actions. Further validation of the isolated compounds would be required in animal studies.

Chemical Constituents of a Marine-derived Fungus Fusarium oxysporum F0888 and their Antibacterial Activity.

Five new compounds, including four hydroxyphenylacetic acid derivatives, stachylines H-K (1-4), a derivative of hydroxyphenylethanol (5), as well as seven known compounds were obtained from a marine-derived fungus Fusarium oxysporum F0888 isolated from sediments in the South China Sea. The structures and absolute configurations of new compounds were determined by spectroscopic (IR, NMR, and HR-ESI-MS) analyses, comparison of optical rotations, and the modified Mosher's MTPA ester method. Antimicrobial and anti-inflammatory activities of compounds 1-12 were tested. Unfortunately, all of isolated compounds were inactivity.

Design, Synthesis, and In Vivo Evaluation of a New Series of Indole-Chalcone Hybrids as Analgesic and Anti-Inflammatory Agents.

Indole-chalcone hybrids have burst into prominence as potent weapons in the battle against pain and inflammation due to their unique features, allowing these ligands to form pivotal interactions with biological targets. In this context, the base-catalyzed Claisen-Schmidt condensation of 3',4'-(methylenedioxy)acetophenone with heteroaromatic aldehydes carrying an indole scaffold yielded new chalcones (1-7). The central and peripheral antinociceptive activities of all chalcones (compounds 1-7) at the dose of 10 mg/kg (i.p.) were evaluated by hot plate (supraspinal response), tail immersion (spinal response), and acetic acid-induced writhing tests in mice. The anti-inflammatory activities of compounds 1-7 were also investigated by means of a carrageenan-induced mouse paw edema model. The results revealed that compounds 1-7 extended the latency of response to thermal stimulus significantly in a hot-plate test similar to dipyrone (300 mg/kg; i.p.), the positive control drug. However, only compounds 2-7 were found to be significantly effective in the tail-immersion test. Compounds 1-7 also significantly showed analgesic effect by reducing the number of writhes and anti-inflammatory activity by inhibiting edema formation at different time intervals and levels. 1-(1,3-Benzodioxol-5-yl)-3-(1-methyl-1H-indol-2-yl)prop-2-en-1-one (4) drew attention by providing the highest efficacy results in both acute analgesia and inflammation models. Based on the in silico data acquired from the QikProp module, compound 4 was predicted to possess favorable oral bioavailability and drug-like properties. Taken together, it can be concluded that chalcones (1-7), especially compound 4, are outstanding candidates for further research to investigate their potential use in the management of pain and inflammation.

In vitro and in silico docking and molecular dynamic of antimicrobial activities, alpha-glucosidase, and anti-inflammatory activity of compounds from the aerial parts of Mussaenda saigonensis.

Twelve compounds were isolated from Mussaenda saigonensis aerial parts through phytochemical analysis and the genus Mussaenda is the first place where the compounds 4-6 and 11-12 have been found. Based on the ability to inhibit NO production in RAW264.7 cells, compound 2 has demonstrated the strongest anti-inflammatory activity in vitro with an IC50 of 7.6 μM, as opposed to L-NMMA's IC50 of 41.3 μM. Compound 12 was found to be the most effective inhibitor of alpha-glucosidase enzyme in vitro, with an IC50 value of 42.4 μM (compared to 168 μM for acarbose). Compounds 1-12 were evaluated in vitro for antimicrobial activity using the paper dish method. Compound 11 demonstrated strong antifungal activity against M. gypseum with a MIC value of 50 μM. In silico docking for antimicrobial activity, pose 90 or compound 11 docked well to the 2VF5 enzyme, PDB, which explains why compound 11 had the highest activity in vitro. Entry 2/pose 280 demonstrated excellent anti-inflammatory activity in silico. The stability of the complex between pose 280 and the 4WCU enzyme for anti-inflammatory activity has been assessed using molecular dynamics over a simulation course ranging from 0 to 100 ns. It has been found to be stable from 60 and 100 ns. The Tyr 159 (95%, H-bond via water bridge), Asp 318 (200%, multiple contacts), Met 273 (75%, hydrophobic interaction via water bridge), and Gln 369 (75%, H-bond via water bridge) interacted well within the time range of 0 to 100 ns. It has more hydrophilic or polar pharmacokinetics.

Megastigmane glycoside and phenol glycosides from the bark of Mallotus barbatus

A new megastigmane glycoside, barbatcoside A (1), and two new phenol glycosides, barbatcosides B (2) and C (3), together with eight known compounds (4-11) were isolated from the bark of Mallotus barbatus Müll. Arg. Their structures were elucidated using extensive 1D and 2D NMR as well as HRESIMS spectroscopic data. The stereochemistry of compounds 1 and 2 were established based on the experimental CD curves. The anti-inflammatory activities of compounds 1-11 from M. barbatus were evaluated using LPS-stimulated RAW 264.7 cell models. Compounds 2 and 3 substantially inhibited the release of NO with IC50 values of 34.78 μM and 20.73 μM, respectively.

One novel alkaloid from the stems of Tinospora crispa

The 6-methoxy-cannabisin I (1), a new alkaloid, together with five known compounds oleraisoindole A (2), cannabisin F (3), apigenin (4), syringin (5) and ethyl-syringin (6) were isolated from Tinospora crispa stems. Their structures were identified by the analysis of spectroscopic data. Compound 2 was isolated from T. crispa for the first time. Anti-inflammatory activity of compound 1 was detected against NO production in LPS-activated RAW 264.7 macrophages. However, no activity was observed.

Two new anti-inflammatory compounds from the roots and rhizomes of Clematis terniflora var. manshurica (Rupr.) Ohwi

Two new compounds named mandshurica A (1) and mandshurica B (2), together with four known lignans (3–6) were isolated from the roots and rhizomes of Clematis terniflora var. manshurica (Rupr.) Ohwi. The structures of the new compounds were elucidated by HR-ESI-MS, 1D and 2D NMR spectroscopy. Moreover, the anti-inflammatory activity of compounds 1 and 2 were evaluated against lipopolysaccharide-induced mouse macrophage RAW264.7 cells. Compounds 1 and 2 displayed significant inhibitory effect on NO production, and compound 2 exhibited obvious inhibition on the pro-inflammatory cytokines TNF-α. Both new compounds showed potential anti-inflammatory activity.

Five new terpenoids from Viburnum odoratissimum var. sessiliflorum.

Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh2(OCOCF3)4-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC50 value of 55.64 μmol·L-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC50 values of 13.8 and 12.3 μmol·L-1, respectively.

Secondary Metabolites with Anti-Inflammatory Activity from Laurencia majuscula Collected in the Red Sea.

The chemical investigation of the organic extract of the red alga Laurencia majuscula collected from Hurghada reef in the Red Sea resulted in the isolation of five C15 acetogenins, including four tricyclic ones of the maneonene type (1-4) and a 5-membered one (5), 15 sesquiterpenes, including seven lauranes (6-12), one cuparane (13), one seco-laurane (14), one snyderane (15), two chamigranes (16, 17), two rearranged chamigranes (18, 19) and one aristolane (20), as well as a tricyclic diterpene (21) and a chlorinated fatty acid derivative (22). Among them, compounds 1-3, 5, 7, 8, 10, 11 and 14 are new natural products. The structures and the relative configurations of the isolated natural products have been established based on extensive analysis of their NMR and MS data, while the absolute configuration of maneonenes F (1) and G (2) was determined on the basis of single-crystal X-ray diffraction analysis. The anti-inflammatory activity of compounds 1, 2, 4-8, 10, 12-16, 18 and 20-22 was evaluated by measuring suppression of nitric oxide (NO) release in TLR4-activated RAW 264.7 macrophages in culture. All compounds, except 6, exhibited significant anti-inflammatory activity. Among them, metabolites 1, 4 and 18 did not exhibit any cytostatic activity at the tested concentrations. The most prominent anti-inflammatory activity, accompanied by absence of cytostatic activity at the same concentration, was exerted by compounds 5 and 18, with IC50 values of 3.69 μM and 3.55 μΜ, respectively.

A new sesquiterpene from stems of Buddleja lindleyana

The present study investigated the chemical constituents from the stems of Buddleja lindleyana. Ten compounds were isolated from the 95% EtOH extract of B. lindleyana stems by means of some techniques including polyamide, silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). Their structures were identified by spectral analysis and single-crystal X-ray diffraction as buddledin F(1), 6-O-4″-hydroxy-3″-methoxy-benzoyl ajugol(2), negundoin G(3),(+)-dihydrocubebin(4), 7-O-ethylguaiacylglycerol(5),(-)-jatrointelignan B(6), threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol(7), vomifoliol(8), hinokinin(9), and isovanillic acid(10). Compound 1 was a new sesquiterpene named buddledin F. Compounds 3-8 were isolated from the Buddleja plant for the first time. The anti-inflammatory activities of compounds 1-10 in vitro were investigated, and the results failed to show the inhibitory activities of these compounds on the production of inflammatory factor NO.

Pseudoamaolides A-O, anti-inflammatory triterpene spiroketal lactones from seeds of Pseudolarix amabilis

Fifteen new triterpenoids (1–15), along with twenty known ones (16–35), were isolated from Pseudolarix amabilis. The triterpenoid structures include multiple skeleton types, such as 2,3-seco-cycloartane, 3,4-seco-cycloartane, 3,4:9,10-diseco-cycloartane, and 3,4:8,9:9,10-triseco-cycloartane, as elucidated by extensive spectroscopy (1D NMR, 2D NMR, HRESIMS, and IR) and single-crystal X-ray diffraction. The anti-inflammatory activities of compounds 1–35 were evaluated. Compounds 3, 11, 16, 24, 25, and 26 suppressed the transcription of the NF-κB-dependent reporter gene in LPS-induced 293T/NF-κB-Luc cells with IC50 values of 0.12, 0.10, 0.30, 0.09, 0.49, and 0.35 μM, respectively. In addition, compound 16 showed anti-inflammatory activity against xylene-induced ear swelling in vivo with an inhibition rate of 44.7 % (30 mg/kg). Compound 16 significantly improved the disease activity index (DAI) of ulcerative colitis at a dose of 400 mg/kg in a dextran sodium sulfate (DSS)-induced mouse model of experimental ulcerative colitis (P < 0.01).

Three New Glycosides From the Stems of Derris elliptica

Three new glycosides, derriacuminosides A-C (1-3), were isolated from the stems of Derris elliptica (Wall.) Benth. Their chemical structures were determined by interpretations of HRESIMS and NMR spectra. The anti-inflammatory activity of compounds 1-3 were evaluated by inhibiting NO production in LPS activated RAW264.7 cells. Compounds 1-3 potentially inhibited NO production with IC50 values of 26.54 ± 3.08, 26.35 ± 1.37, and 49.71 ± 2.93 µM, respectively, compared to the positive control, L-NMMA (IC50 35.56 ± 2.98 µM).

Targeted Isolation of Anti-inflammatory Lignans from Justicia aequilabris by Molecular Networking Approach.

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MSn and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C (1-3)) and three known compounds (lariciresinol-4'-O-β-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1-3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1β. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 μM, respectively. The maximum inhibition of IL-1β production was 23.5% (1), 27.3% (2), and 32.5% (3).

Anti-inflammatory withajardins from the leaves of Athenaea velutina

Withajardins, uncommon modified withanolide-type steroids, have been isolated exclusively from plants of the Solanaceae family so far. Two undescribed withajardins and the known tuboanosigenin were isolated from the hexane/EtOAc 1:1 extract from Athenaea velutina leaves. Their structures were established by an extensive analysis of 1D and 2D-NMR and HRMS data. The absolute configuration was determined by X-ray diffraction (withajardin L and tuboanosigenin) and circular dichroism (CD) analyses (withajardin M). The anti-inflammatory activity of compounds was evaluated through the inhibition of the lipopolysaccharide (LPS)-induced nitric oxide (NO), TNF-α, and IL-6 release in RAW264.7 cells. The cell viability effects to RAW 264.7 cells showed IC50 values of 74.4–354.4 μM. The compounds attenuated LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 in RAW264.7 cells.

Artemisiaside A: A new Lignan Glycoside and its Analogues From the Aerial Parts of Artemisia argyi

Chemical analysis of the aerial parts of Artemisia argyi H. Lév. &amp; Vaniot led to the isolation of 6 lignans, including a new lignan glycoside, artemisiaside A, using various chromatographic techniques. Detailed spectroscopic (including 1D, 2D- nuclear magnetic resonance) and high resolution mass spectroscopy procedures, and electronic circular dichroism were used to ascertain the structural orientations of these compounds. The anti-inflammatory activities of compounds 1 to 6 were evaluated by measuring their inhibitory effects on lipopolysaccharide (LPS) -induced nitric oxide (NO) production in RAW264.7 LPS-activated macrophages. At 50 μM, compound 1 showed moderate anti-inflammatory activity with an inhibition rate of 61.2%.