Exploring the chemical diversity of sesquiterpenes from the rarely studied South China Sea soft coral Sinularia tumulosa assisted by molecular networking strategy.

Molecular networking strategy-based prioritization of the isolation of the rarely studied soft coral Sinularia tumulosa yielded 14 sesquiterpenes. These isolated constituents consisted of nine different types of carbon frameworks, namely asteriscane, humulane, capillosane, seco-asteriscane, guaiane, dumortane, cadinane, farnesane, and benzofarnesane. Among them, situmulosaols A-C (1, 3 and 4) were previously undescribed ones, whose structures with absolute configurations were established by the combination of extensive spectral data analyses, quantum mechanical-nuclear magnetic resonance and time-dependent density functional theory electronic circular dichroism calculations, the Snatzke's method, and the modified Mosher's method. Notably, situmulosaol C (4) was the second member of capillosane-type sesquiterpenes. The plausible biogenetic relationships of these skeletally different sesquiterpenes were proposed. All sesquiterpenoids were evaluated for their antibacterial, cytotoxic and anti-inflammatory effects. The bioassay results showed compound 14 exhibited significant antibacterial activities against a variety of fish and human pathogenic bacteria with MIC90 values ranging from 3.6 to 33.8 µg/mL. Moreover, moderate cytotoxic effects against HEL cells for components 13 and 14 and moderate inhibitory effect on lipopolysaccharide-induced inflammatory responses in RAW264.7 cells for substance 13 were also observed.

Bi-2-(2-phenethyl)chromone derivatives from agarwood of Aquilaria filaria in the Philippines.

Twelve undescribed 2-(2-phenethyl)chromone dimers (1-12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9-12 exhibited potent to moderate anti-inflammatory activity with IC50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 µM.

Potential in-vitro antioxidant and anti-inflammatory activity of Martynia annua extract mediated Phytosynthesis of MnO2 nanoparticles.

The present research work describes the phyto-synthesis of Manganese dioxide nanoparticles (MnO2NPs) from the reduction of potassium permanganate using Martynia annua (M.annua) plant extract. From the literature review, we clearly understood the M.annua plant has anti-inflammatory activity. Manganese dioxides are important materials due to their wide range of applications. Their increased surface area gives them distinct capabilities, as it increases their mechanical, magnetic, optical, and catalytic qualities, allowing them to be used in more pharmaceutical applications. A detailed review of literature highlighting the issues related to this present work and its knowledge gap that none of the inflammatory activities had been done by MnO2 NPs synthesized from M.annua plant extract. So we selected this study. The product MnO2 NPs showed the wavelength centre at 370 nm and was monitored by UV-Vis spectra. The wave number around 600 cm-1 has to the occurrence of O-Mn-O bonds of pure MnO2 confirmed by FTIR spectroscopy. Transmission electron microscopy images showed the morphology of MnO2 NPs as spherical-shaped particles with average sizes at 7.5 nm. The selected area electron diffraction analysis exhibits the crystalline nature of MnO2 NPs. The obtained MnO2 NPs showed potential antioxidant and anti-inflammatory activity was compared to the plant extract. The synthesized MnO2 NPs have a large number of potential applications in the field of pharmaceutical industries. In the future, we isolate the phytocompounds present in the M.annua plant extract and conduct a study against corona virus. MnO2 produces manganese (III) oxide and oxygen, which increases fire hazard. But further research is required to understand their environmental behaviour and safety.

Design, synthesis, biological and computational screening of novel pyridine-based thiadiazole derivatives as prospective anti-inflammatory agents.

In this study, a novel series of pyridine-based thiadiazole derivatives (NTD1-NTD5) were synthesized as prospective anti-inflammatory agents by combining substituted carboxylic acid derivatives of 5-substituted-2-amino-1,3,4-thiadiazole with nicotinoyl isothiocyanate in the presence of acetone. The newly synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, and mass spectrometry. First, the compounds underwent rigorous in vivo testing for acute toxicity and anti-inflammatory activity and the results revealed that three compounds-NTD1, NTD2, and NTD3, displayed no acute toxicity and significant anti-inflammatory activity, surpassing the efficacy of the standard drug, diclofenac. Notably, NTD3, which featured benzoic acid substitution, emerged as the most potent anti-inflammatory agent among the screened compounds. To further validate these findings, an in silico docking study was carried out against COX-2 bound to diclofenac (PDB ID: 1pxx). The computational analysis demonstrated that NTD2, and NTD3, exhibited substantial binding affinity, with the lowest binding energies (-8.5 and -8.4, kcal/mol) compared to diclofenac (-8.4 kcal/mol). This alignment between in vivo and in silico data supported the robust anti-inflammatory potential of these derivatives. Moreover, molecular dynamics simulations were conducted, extending over 100 ns, to examine the dynamic interactions between the ligands and the target protein. The results solidified NTD3's position as a leading candidate, showing potent inhibitory activity through strong and sustained interactions, including stable hydrogen bond formations. This was further confirmed by RMSD values of 2-2.5 Å and 2-3Ǻ, reinforcing NTD3's potential as a useful anti-inflammatory agent. The drug likeness analysis of NTD3 through SwissADME indicated that most of the predicted parameters including Lipinski rule were within acceptable limits. While these findings are promising, further research is necessary to elucidate the precise relationships between the chemical structures and their activity, as well as to understand the mechanisms underlying their pharmacological effects. This study lays the foundation for the development of novel anti-inflammatory therapeutics, potentially offering improved efficacy and safety profiles.

A New 4-Thiazolidinone Derivative (Les-6490) as a Gut Microbiota Modulator: Antimicrobial and Prebiotic Perspectives.

A novel 4-thiazolidinone derivative Les-6490 (pyrazol-4-thiazolidinone hybrid) was designed, synthesized, and characterized by spectral data. The compound was screened for its antimicrobial activity against some pathogenic bacteria and fungi and showed activity against Staphylococcus and Saccharomyces cerevisiae (the Minimum Inhibitory Concentration (MIC) 820 µM). The compound was studied in the rat adjuvant arthritis model (Freund's Adjuvant) in vivo. Parietal and fecal microbial composition using 16S rRNA metagenome sequences was checked. We employed a range of analytical techniques, including Taxonomic Profiling (Taxa Analysis), Diversity Metrics (Alpha and Beta Diversity Analysis), Multivariate Statistical Methods (Principal Coordinates Analysis, Principal Component Analysis, Non-Metric Multidimensional Scaling), Clustering Analysis (Unweighted Pair-group Method with Arithmetic Mean), and Comparative Statistical Approaches (Community Differences Analysis, Between Group Variation Analysis, Metastat Analysis). The compound significantly impacted an increasing level of anti-inflammatory microorganisms (Blautia, Faecalibacterium prausnitzii, Succivibrionaceae, and Coriobacteriales) relative recovery of fecal microbiota composition. Anti-Treponemal activity in vivo was also noted. The tested compound Les-6490 has potential prebiotic activity with an indirect anti-inflammatory effect.

Diterpenoid glucosides with anti-inflammatory activity from Sigesbeckia glabrescens.

Six previously undescribed diterpenoid glucosides, along with four known compounds, were isolated from the aerial parts of Sigesbeckia glabrescens. The structures and absolute configurations of undescribed compounds were elucidated using extensive spectroscopic techniques, ECD calculations and chemical methods. Compounds 1 and 8 exhibited anti-inflammatory activity against LPS-induced NO production in RAW 264.7 macrophages, with compound 8 demonstrating significant inhibitory activity compared to positive control minocycline, boasting an IC50 value at 14.20 µM.

Production, characterisation, and biological properties of Tenebrio molitor-derived oligopeptides.

Three protein hydrolysates from Tenebrio molitor were obtained by enzymatic hydrolysis employing two food-grade proteases (i.e. Alcalase and Flavourzyme), and a complete characterisation of their composition was done. The digestion-derived products were obtained using the INFOGEST protocol. In vitro antioxidant activity and anti-inflammatory activities were evaluated. Tenebrio molitor flour and the protein hydrolysates showed a high ability to scavenge the DPPH radical (EC50 values from 0.30 to 0.87 mg/mL). The hydrolysate obtained with a combination of the two food-grade proteases could decrease the gene expression of pro-inflammatory genes after being digested. Furthermore, the peptidome was fully determined for the first time for T. molitor hydrolysates and digests, and 40 peptides were selected based on their bioactivity to be evaluated by in silico tools, including prediction tools and molecular docking. These results provide new perspectives on the use of edible insects as sustainable and not nutritionally disadvantageous food for human consumption.

[Analysis of constituents in different parts of Forsythia suspensa by UPLC-Q-TOF-MS and evaluation of their anti-inflammatory activity].

This study aims to characterize and identify the chemical constituents in 11 parts of Forsythia suspensa by using ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with a self-established chemical constituent database, including leaves, flowers, fruits, green F. suspensa, old F. suspensa, and seeds. The quality attributes and differences of different parts of F. suspensa were evaluated by principal component analysis, partial least square discriminant analysis, and other stoichiometric methods. A total of 79 compounds were identified, including 13 phenylethanol glycosides, 10 lignans, 12 flavonoids, 10 organic acids, 14 terpenoids, and 20 other types of compounds. Among them, 34 compounds were the main variables of difference between the different parts of F. suspensa, and the content of each component was relatively higher in the leaves and green F. suspensa. The LPS-induced inflammation model of RAW264.7 cells was applied to study the anti-inflammatory activity of the extracts of the different parts of F. suspensa and the main constituents. The results show that the extracts of green F. suspensa, flower, twig, and stem exhibited anti-inflammatory activity, and the constituents such as forsythoside A, phyllyrin, phillygenin, and(+)-pinoresinol-ß-D-glucopyranoside could significantly inhibit anti-inflammatory activity released by NO. The chemical constituent in different parts of F. suspensa is analyzed comprehensively, and the anti-inflammatory activity is evaluated in this study, which provides a reference for the development and comprehensive utilization of F. suspensa resources.

[A new sesquiterpenoid from Lindera aggregata].

The chemical composition of the aqueous part of the extract from Lindera aggregata was studied, which was separated and purified by the macroporous resin column chromatography, MCI medium pressure column chromatography, semi-preparative high-performance liquid phase and other methods. The structures of the compounds were identified according to physical and chemical properties and spectroscopic data. Thirteen compounds were isolated and identified from the aqueous extracts, which were identified as(1S,3R,5R,6R,8S,10S)-epi-lindenanolide H(1), tachioside(2), lindenanolide H(3), leonuriside A(4), 3,4-dihydroxyphenyl ethyl ß-D-glucopyranoside(5), 3,4,5-trimethoxyphenol-1-O-6-α-L-rhamnose-(1→6)-O-ß-D-glucoside(6), 5-hydroxymethylfurfural(7),(+)-lyoniresin-4-yl-ß-D-glucopyranoside(8), lyoniside(9), norboldine(10), norisopordine(11), boldine(12), reticuline(13). Among them, compound 1 was a new one, and compounds 2, 5, 6, 8, 9 were obtained from L. aggregata for the first time. The inflammatory model was induced by lipopolysaccharide(LPS) in the RAW264.7 cells. The results showed that compounds 1, 8, 10 and 12 had significant anti-inflammatory activity.

[Highly polar chemical constituents from whole herb of Scindapsus officinalis].

Macroporous resin column chromatography, MCI medium pressure column chromatography, and semi-preparative high performance liquid chromatography were employed to isolate the chemical components from the aqueous extract of the whole herb of Scindapsus officinalis. The structures of the compounds were identified based on the physical and chemical properties and the spectroscopic data. Ten compounds were isolated from the aqueous extract and identified as 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1→4)]-ß-D-glucopyranoside(1), alternamide B(2), 3,4-dihydroxyphenylethyl-O-ß-D-glucopyranoside(3), 1-(4-hydroxy)-phenylethyl-ß-D-galactopyranoside(4), 3,4-dihydroxyphenylethyl-8-O-[ß-D-apiofuranosyl-(1→2)]-ß-D-glucopyranoside(5), hydroxytyrosol-4-O-ß-D-glucopyranoside(6), 3,5-dihydroxyphenylethyl-3-O-ß-D-glucopyranoside(7), salidroside(8), dihydroisoquinolone(9), and 4-methoxybenzenepropanol-3-O-ß-D-glucopyranoside(10). Among them, compound 1 was a new one, and compounds 2-10 were obtained from S. officinalis for the first time. The RAW264.7 cells were exposed to lipopolysaccharide for the mode-ling of inflammation, and the cells were then used to examine anti-inflammatory activities of the compounds. The results showed that compounds 6 and 7 had strong anti-inflammatory activities, while compounds 1, 2, and 5 had moderate anti-inflammatory activities.

Anti-inflammatory monomeric sorbicillinoids from the marine-fish-derived fungus Trichoderma sp. G13.

Four new monomeric sorbicillinoids, trichillinoids A - D (1-4), along with two known dimeric sorbicillinoids (5 and 6), and five known monomeric sorbicillinoids (7-11), were obtained from the marine-fish-derived fungus Trichoderma sp. G13. They were structurally characterized on the basis of comprehensive spectroscopic investigations (NMR, HRESIMS, and ECD). Compounds 1-4 displayed moderate anti-inflammatory activities, according to inhibiting the production of NO in RAW264.7 cells activated with IC50 values ranging from 14 to 20 µM.

Anti-inflammatory steroids from the South China Sea Sponge Spongia officinalis.

One new highly degraded steroid, namely 21-nor-4-ene-chaxine A (1) furnishing a 5/6/5-tricyclic, along with one known related analogue (2), were isolated from the South China Sea sponge Spongia officinalis. Their structures including absolute configurations were established by extensive spectroscopic data analysis, TDDFT-ECD calculation, and comparison with the spectral data previously reported in the literature. Compound 1 represent the new member of incisterols family with a highly degradation in ring B. In vitro bioassays revealed compound 2 exhibited significant anti-microglial inflammatory effect on lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells.

Terminalia ferdinandiana Exell. extracts reduce pro-inflammatory cytokine and PGE2 secretion, decrease COX-2 expression and down-regulate cytosolic NF-κB levels.

Based on their high antioxidant capacity and noteworthy phytochemistry, Terminalia ferdinandiana fruit and leaves have attracted considerable recent interest for their therapeutic potential. Whilst those studies have reported a variety of therapeutic properties for the fruit, the anti-inflammatory potential of T. ferdinandiana has been largely neglected and the leaves have been almost completely ignored. This study investigated the immune-modulatory and anti-inflammatory properties of T. ferdinandiana fruit and leaf extracts by evaluating their inhibition of multiple pro- and anti-inflammatory cytokines and chemokines secretion in lipopolysaccharide (LPS)-stimulated and unstimulated RAW 264.7 macrophages using multiplex bead immunoassays and ELISA assays. The methanolic extracts were particularly good immune-modulators, significantly inhibiting the secretion of all the cytokines and chemokines tested. Indeed, the methanolic extracts completely inhibited IL-10, IFN-γ, IL-1ß, IL-6, MCP-1, and MIP-2a secretion, and almost completely inhibited the secretion of TNF-α. In addition, the methanolic T. ferdinandiana extracts also significantly inhibited cytosolic COX-2 levels (by 87-95%) and the synthesis of the PGE2 (by ~ 98%). In contrast, the methanolic extracts stimulated LTB4 secretion by ~ 60-90%, whilst the aqueous extracts significantly inhibited LTB4 secretion (by ~ 27% each). Exposure of RAW 264.7 cells to the methanolic T. ferdinandiana extracts also significantly down-regulated the cytosolic levels of NF-κB by 33-44%, indicating that the immune-modulatory and anti-inflammatory properties of the extracts may be regulated via a decrease in NF-κB transcription pathways. Taken together, these results demonstrate potent anti-inflammatory properties for the extracts and provide insights into their anti-inflammatory mechanisms.

Discovery of novel ocotillol derivatives modulating glucocorticoid receptor/NF-κB signaling for the treatment of sepsis.

Glucocorticoids (GCs) have been used in the treatment of sepsis because of their potent anti-inflammatory effects. However, their clinical efficacy against sepsis remains controversial because of glucocorticoid receptor (GR) downregulation and side effects. Herein, we designed and synthesized 30 ocotillol derivatives and evaluated their anti-inflammatory activities. Ocotillol 24(R/S) differential isomers were stereoselective in their pharmacological action. Specifically, 24(S) derivatives had better anti-inflammatory activity than their corresponding 24(R) derivatives. Compound 20 most effectively inhibited NO release (85.97% reduction), and it exerted dose-dependent inhibitory effects on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels. Mechanistic studies revealed that compound 20 reduces the degradation of GR mRNA and GR protein. Meanwhile, compound 20 inhibited the activation of nuclear factor-κB (NF-κB) signaling, thereby inhibiting the nuclear translocation of p65 and attenuating the inflammatory response. In vivo studies revealed that compound 20 attenuated hepatic, pulmonary, and renal pathology damage in mice with sepsis and suppressed the production of inflammatory mediators. These results indicated that compound 20 is a promising lead compound for designing and developing anti-sepsis drugs.

Two new alkaloids from Portulaca oleracea L. and their anti-inflammatory and anticholinesterase activities.

Two new alkaloids identified as 2-(((S,Z)-1-(1H-azirin-1-yl)-5-methylhex-1-en-3-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol and (S,Z)-1-(1H-azirin-1-yl)-5-methylhex-1-en-3-ol, named olerazirin A (1), olerazirin B (2), together with five known alkaloids, identified as cyclo (L-Val-L-Ala) (3), cyclo-(glycyl-L-leucine) (4), cyclo-(Gly-Phe) (5), cyclo (Ser-Phe) (6), (3S,6S)-3-[(1R)-1-hydroxyethyl]-6-(phenyl-methyl)-2,5-piperazinedione (7) were obtained from Portulaca oleracea L. using a range of chromatographic techniques, 1D and 2D NMR, and high-resolution electrospray ionisation time-of-flight mass spectroscopic methods, in which the compounds 3-7 were isolated from P. oleracea for the first time. In addition, the results showed that the compounds 1 and 2 have anti-inflammatory activities and compounds 1-3 and 5-7 exhibit the anticholinesterase activities.

Two undescribed coumarins from Hansenia weberbaueriana.

Two previously undescribed coumarins (1 and 2) were isolated from the root of Hansenia weberbaueriana which have been used to cure inflammatory diseases over thousands of years by Chinese. The structures of new findings were confirmed by comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR combined with chemical calculations. Compounds 1 and 2 exhibited potential anti-inflammatory properties by reducing the mRNA expression levels of TNF-α, IL-6 and IL-1ß in lipopolysaccharide (LPS)-induced RAW264.7 macrophages at a concentration of 15 µM.

New eremophilane-type sesquiterpenes from Synotis solidaginea.

Eleven new highly oxygenated eremophilane-type sesquiterpenoids were isolated from the whole plant of Synotis solidaginea, including two pairs of C-8 S/R epimers. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configuration of 1 and 9 was confirmed by single-crystal X-ray crystallography using Cu Kα radiation. All the isolates were tested for the inhibition of LPS-stimulated NO production in macrophage-like mouse monocytic leukemia RAW264.7 cells. Compound 1 exhibited weak inhibitory effects with an IC50 of 71.2 µM.

N,N-Diarysulfonamide reduces proinflammatory cytokine interleukin-6 levels in cells through nuclear factor-κB regulation.

The synthesized sulfonamides were evaluated for cytotoxicity followed by the cytokine/inflammatory marker's inhibition capability and its mechanism of action in RAW-264.7 cells. Elevated interleukin-6 (IL-6) levels have been reported in inflammatory conditions and inflammation-associated disorders. Hence, reducing the IL-6 levels in inflammatory conditions can serve as an attractive therapeutic target in dealing the inflammation. Among 42 compounds, seven compounds showed significant inhibition of IL-6 levels in lipopolysaccharide (LPS) challenged RAW-264.7 cells at 12.5 µM concentration. Further, investigation revealed that the IC50 value of these compounds for reducing IL-6 levels was found to be in the range of 9.7 to 2.6 µM. The promising compounds 5y (IC50 of 2.6 µM) and 5n (IC50 of 4.1 µM) along with other derivatives fulfil drug-likeness parameters laid down by Lipinski's rule of five. Further, analysis using RTqPCR and Western-blot analysis revealed that treatment with 5n significantly reduced the expression of pro-inflammatory, inflammatory and macrophage marker's expression (IL-1ß, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that RL-442 exhibited anti-inflammatory properties by modulating the nuclear factor-κB (NF-κB) activation. The identified compound can be a promising candidate for further discovery efforts to generate a preclinical candidate effective in inflammation.

Chitosan/Pomegranate Seed Oil Emulgel Composition as a New Strategy for Dermal Delivery of Hydrocortisone.

Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharmacological activity have attracted particular attention. Chitosan (CS) and pomegranate seed oil (PO) appear to be attractive bioactive components framing the strategy of complex therapy and multifunctional drug carriers. This research is aimed at evaluating the potential of CS in combination with PO in studies on topical emulgels containing hydrocortisone as a model anti-inflammatory agent. Its particular goal was to distinguish alterations in anti-inflammatory action followed with drug dissolution or penetrative behavior between the designed formulations that differ in CS/PO weight ratio. All formulations favored hydrocortisone release with up to a two-fold increase in the drug dissolution rate within first 5 h as compared to conventional topical preparations. The clear effect of CS/PO on the emulgel biological performance was observed, and CS was found to be prerequisite for the modulation of hydrocortisone absorption and accumulation. In turn, a greater amount of PO played the predominant role in the inhibition of hyaluronidase activity and enhanced the anti-inflammatory effect of preparation E-3. Emulgels showed a negligible reduction in mouse fibroblasts' L929 cell viability, confirming their non-irritancy with skin cells. Overall, the designed formulation with a CS/PO ratio of 6:4 appeared to be the most promising topical carrier for the effective treatment of inflammatory skin diseases among the tested subjects.

Elucidation of antioxidant activities of intracellular and extracellular polysaccharides from Cordyceps militaris in vitro and their protective effects on ulcerative colitis in vivo.

In this study, we extracted the polysaccharides from C. militaris fruiting bodies (CFIPs), mycelial intracellular polysaccharides (CMIPs), and fermentation broth extracellular polysaccharides (CFEPs) to investigate their physicochemical properties, antioxidant capacities, and effects on oxazolone-induced zebrafish ulcerative colitis (UC). Our results revealed differences in monosaccharide composition and surface structure among CFIPs, CMIPs, and CFEPs. The molar ratios of glucose to mannose in CFIPs, glucose to xylose in CMIPs, and xylose to glucose in CFEPs were 7.57: 1.6, 7.26: 1.81, and 5.44: 2.98 respectively. Moreover, CFEPs exhibited significantly (p < 0.05) higher chemical antioxidant capacity compared to CMIPs and CFIPs. Surprisingly, CFEP treatment didn't show a significant effect in protecting against H2O2-induced oxidative damage in RAW 264.7 cells. After 3 d of treatment, the levels of ROS, MDA, and MPO in the CFIPs group exhibited a significant (p < 0.05) reduction by 37.82 %, 68.15 %, and 22.77 % respectively. Additionally, the ACP and AKP increased by 60.33 % and 96.99 %. Additionally, C. militaris polysaccharides (CMPs) were found to effectively improve UC by activating the MyD88/NF-κB signaling pathway in vivo. These findings confirm the distinct physicochemical properties of these three types of CMP and their potential for development into antioxidant-rich anti-inflammatory health foods.