Anti-inflammatory Screening Research Articles

Pharmacological and behavioral investigation of putative self-medicative plants in Budongo chimpanzee diets.

Wild chimpanzees consume a variety of plants to meet their dietary needs and maintain wellbeing. While some plants have obvious value, others are nutritionally poor and/or contain bioactive toxins which make ingestion costly. In some cases, these nutrient-poor resources are speculated to be medicinal, thought to help individuals combat illness. In this study, we observed two habituated chimpanzee communities living in the Budongo Forest, Uganda, and collected 17 botanical samples associated with putative self-medication behaviors (e.g., bark feeding, dead wood eating, and pith-stripping) or events (e.g., when consumer had elevated parasite load, abnormal urinalysis, or injury). In total, we selected plant parts from 13 species (nine trees and four herbaceous plants). Three extracts of different polarities were produced from each sample using n-hexane, ethyl acetate, and methanol/water (9/1, v/v) and introduced to antibacterial and anti-inflammatory in vitro models. Extracts were evaluated for growth inhibition against a panel of multidrug-resistant clinical isolates of bacteria, including ESKAPE strains and cyclooxygenase-2 (COX-2) inhibition activity. Pharmacological results suggest that Budongo chimpanzees consume several species with potent medicinal properties. In the antibacterial library screen, 45 out of 53 extracts (88%) exhibited ≥40% inhibition at a concentration of 256 μg/mL. Of these active extracts, 41 (91%) showed activity at ≤256μg/mL in subsequent dose-response antibacterial experiments. The strongest antibacterial activity was achieved by the n-hexane extract of Alstonia boonei dead wood against Staphylococcus aureus (IC50: 16 μg/mL; MIC: 32 μg/mL) and Enterococcus faecium (IC50: 16 μg/mL; MIC: >256 μg/mL) and by the methanol-water extract of Khaya anthotheca bark and resin against E. faecium (IC50: 16 μg/mL; MIC: 32 μg/mL) and pathogenic Escherichia coli (IC50: 16 μg/mL; MIC: 256 μg/mL). We observed ingestion of both these species by highly parasitized individuals. K. anthotheca bark and resin were also targeted by individuals with indicators of infection and injuries. All plant species negatively affected growth of E. coli. In the anti-inflammatory COX-2 inhibition library screen, 17 out of 51 tested extracts (33%) showed ≥50% COX-2 inhibition at a concentration of 5 μg/mL. Several extracts also exhibited anti-inflammatory effects in COX-2 dose-response experiments. The K. anthotheca bark and resin methanol-water extract showed the most potent effects (IC50: 0.55 μg/mL), followed by the fern Christella parasitica methanol-water extract (IC50: 0.81 μg/mL). This fern species was consumed by an injured individual, a feeding behavior documented only once before in this population. These results, integrated with associated observations from eight months of behavioral data, provide further evidence for the presence of self-medicative resources in wild chimpanzee diets. This study addresses the challenge of distinguishing preventative medicinal food consumption from therapeutic self-medication by integrating pharmacological, observational, and health monitoring data-an essential interdisciplinary approach for advancing the field of zoopharmacognosy.

Extraction, characterization, antioxidation and anti-inflammatory activity of polysaccharides from Bupleurum chinense based on different molecular weights

Bupleurum chinense polysaccharide has a wide range of biological activities. In this study, Bupleurum chinense polysaccharides (BPs), BPs-1 (30 kDa) and BPs-2 (2000 kDa) with different molecular weights were isolated and prepared by ultrafiltration interception method. The structures of BPs, BPs-1 and BPs-2 were characterised by monosaccharide composition, GC-MS, Fourier transform infra-red spectroscopy and nuclear magnetic resonance. The results showed that the monosaccharide composition of BPs with different molecular weights was the same, but the proportion was different. BPs, BPs-1 and BPs-2 were mainly connected by Glup-(1→,→2,4)-Araf-(1→,→6)-Glup-(1→). The anti-inflammatory activity screening experiment in vitro showed that BPs-1 had stronger anti-inflammatory effect. Antioxidant experiments showed that BPs-2 had high free radical scavenging activity. This study laid a foundation for elucidating the fine structure and structure-activity relationship of Bupleurum chinense polysaccharides and will promote the product development of Bupleurum chinense polysaccharides.

A new anti-inflammatory lupane in Ziziphus jujuba (L.) Gaertn. var. hysudrica Edgew.

ObjectivesTo investigate extracts of the stem bark of Ziziphus jujuba (L.) Gaertn. var. hysudrica Edgew. (Rhamnaceae) for anti-inflammatory activity and isolate the active principle(s). MethodsThe dry powder was macerated separately in three types of solvents to prepare methanol extract (ME), ethyl acetate extract (EE), and chloroform extract (CE). Following in vitro anti-inflammatory screening, the most active extract was selected to isolate the active compound. Both, the active extract and isolated compound were further tested on rats using the carrageenan-induced inflammation model. The blood and paw tissue were subjected to qPCR, and histopathology, respectively. Key findingsCE showed comparatively higher anti-inflammatory activity (85.0–95.0 %) in all in vitro assays, except the heat-induced membrane stabilization model (p < 0.05), and upon column chromatography, it yielded a pure crystalline compound. The compound was a pentacyclic triterpenoid (Lupane), named as hydroxymethyl (3β)-3-methyl-lup-20(29)-en-28-oate (Hussainate). CE (500 mg/kg) and Hussainate (1.0 mg/kg) reduced edema in 5 h after carrageenan administration. The activity of Hussainate was found to be comparable to that of dexamethasone (standard). The possible activity mechanism was the downregulation of tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-II), NF-κB, and IL-1β. ConclusionsThis study reveals that chloroform extract of the stem's bark of Z. jujuba may be used to prepare standardized anti-inflammatory herbal products using Hussainate as an active analytical marker. Hussainate may be used as a lead to develop anti-inflammatory drugs.

Anti-inflammatory Polyketides from an Endophytic Fungus Chaetomium sp. UJN-EF006 of Vaccinium bracteatum.

Seven new polyketides including three chromone derivatives (1-3) and four linear ones incorporating a tetrahydrofuran ring (4-7), along with three known compounds (8-10), were obtained from the fermentation of an endophytic fungus (Chaetomium sp. UJN-EF006) isolated from the leaves of Vaccinium bracteatum. The structures of these fungal metabolites have been elucidated by spectroscopic means including MS, NMR and electronic circular dichroism. A preliminary anti-inflammatory screening with the lipopolysaccharide (LPS) induced RAW264.7 cell model revealed moderate NO production inhibitory activity for compounds 1 and 4. In addition, the expression of three LPS-induced inflammatory factors IL-6, iNOS and COX-2 was also blocked by 1 and 4.

Antiedematogenic and Analgesic Activities of Abietic Acid in Mice.

Exacerbated inflammatory responses to harmful stimuli can lead to significant pain, edema, and other complications that require pharmacological intervention. Abietic acid (AA) is a diterpene found as a significant constituent in pine species, and evidence has identified its biological potential. The present study aimed to evaluate abietic acid's antiedematogenic and anti-inflammatory activity in mice. Swiss mice (Mus musculus) weighing 20-30 g were treated with AA at 50, 100, and 200 mg/kg. The central nervous system (CNS) effects were evaluated using open-field and rotarod assays. The antinociceptive and anti-inflammatory screening was assessed by the acetic acid and formalin tests. The antiedematogenic activity was investigated by measuring paw edema induced by carrageenan, dextran, histamine, arachidonic acid, and prostaglandin, in addition to using a granuloma model. The oral administration of abietic acid (200 mg/Kg) showed no evidence of CNS effects. The compound also exhibited significant antiedematogenic and anti-inflammatory activities in the carrageenan and dextran models, mostly related to the inhibition of myeloperoxidase (MOP) activity and histamine action and, to a lesser extent, the inhibition of eicosanoid-dependent pathways. In the granuloma model, abietic acid's effect was less expressive than in the acute models investigated in this study. In conclusion, abietic acid has analgesic and antiedematogenic activities related to anti-inflammatory mechanisms.

Bioprospecting-based untargeted metabolomics identifies alkaloids as potential anti-inflammatory bioactive markers of Ocotea species (Lauraceae).

Species within the Ocotea genus (Lauraceae), have demonstrated an interesting profile of bioactivities. Renowned for their diverse morphology and intricate specialized metabolite composition, Ocotea species have re-emerged as compelling candidates for bioprospecting in drug discovery research. However, it is a genus insufficiently studied, particularly regarding anti-inflammatory activity. To investigate the anti-inflammatory activity of Ocotea spp. extracts and determine the major markers in this genus. Extracts of 60 different Ocotea spp. were analysed by an ex vivo anti-inflammatory assay in human whole blood. The experiment estimates the prostaglandin E2 levels, which is one of the main mediators of the inflammatory cascade, responsible for the classical symptoms of fever, pain, and other common effects of the inflammatory process. Untargeted metabolomics analysis through liquid chromatography coupled with high-resolution mass spectrometry was performed, along with statistical analysis, to investigate which Ocotea metabolites are correlated with their anti-inflammatory activity. The anti-inflammatory screening indicated that 49 out of 60 Ocotea spp. extracts exhibited significant inhibition of PGE2 release compared to the vehicle (p < 0.05). Furthermore, 10 of these extracts showed statistical similarity to the reference drugs. The bioactive markers were accurately identified using multivariate statistics combined with a fold change (> 1.5) and adjusted false discovery rate analysis as unknown compounds and alkaloids, with a majority of aporphine and benzylisoquinolines. These alkaloids were annotated with an increased level of confidence since MSE spectra were compared with comprehensive databases. This study represents the first bioprospecting report revealing the anti-inflammatory potential of several Ocotea spp. The determination of their anti-inflammatory markers could contribute to drug discovery and the chemical knowledge of the Ocotea genus.

The anticancer and anti-inflammatory activity screening of pyridazinone-based analogs against human epidermoid skin cancer with detailed mechanistic analyses

3(2H)-Pyridazinone derivatives based on 4-biphenyl, naphtha-2-yl, pyridine, or piperidine moiety were synthesized and characterized using I-R and 1HNMR spectra. The activity and cytotoxicity of some synthesized compounds on the skin epidermoid cancer cell proliferation and progression were investigated. The pyridazine isomer with pyridine revealed a significant decrease in the level of nitric oxide p < 0.01 than the activity of caffeine phenecyl ester. The activity of the three active isomers recorded significant activity for their total antioxidant content that triggers their ability for the scavenging the oxygen free radicals significantly p < 0.01. Moreover, revealing the pharmaceutical activity of the isomers as anti-inflammatory agents, IL-6, IL10, and IL12 have been decreased by variable significant values. Additionally, the active isomers revealed variable actions on the skin cancer cell to induce apoptosis using annexin V-FITC/PI. Pyridine was the highest isomer to induce late apoptosis and necrosis for the skin cancer cells against the use of cisplatin. Importantly, Molecular modeling experiments including docking and dynamic simulations were done for the most active 3 analogs to explore the ligand binding and stability leading to exploring the structure-activity relationship with biological target PARP1 which showed a good binding propensity to pyridazine binding site which supports the in vitro data. In conclusion, the pyridazine moieties with piperdine, naphthayl, and pyridine have pharmacological activities against skin cancer epidermoid by triggering action in inhibition of the proliferation and progression with an up-regulated apoptotic mechanism that evades the emergence of cisplatin resistance among different cancer cells. Communicated by Ramaswamy H. Sarma

Anti-inflammatory probiotic Lactiplantibacillus plantarum HF05 screening from Qula: Genomic analysis and alleviating effect on intestinal inflammation

The use of probiotics for their anti-inflammatory potential is an area with limited research, and there is currently limited understanding of the connection between the genotype and phenotype of the majority of probiotics. In this study, Lactiplantibacillus plantarum HF05 with prominent anti-inflammatory effects and excellent probiotic characteristics was screened from Qula by combining RAW264.7 inflammatory cell model screening with in vitro comparison of probiotic properties. Through whole genome analysis, we found that the HF05 genome encoded a large number of environmental adaptation, adhesion, colonization, anti-inflammatory and antioxidant-related genes. The in vitro experiments demonstrated that HF05 inhibited pro-inflammatory cytokine release in RAW264.7 inflammatory cells. Furthermore, we found that prophylactic intake of HF05 alleviated intestinal inflammation and oxidative damage in mice with acute colitis and inhibited the value-added of enteropathogenic bacteria (Escherichia coli, Enterococcus faecalis, Staphylococcus xylosus) and reversed the depletion of Lactobacillus (Lactobacillus johnsonii, Lactobacillus intestinalis). Collectively, we demonstrated that HF05 can serve as a new probiotic for the relief of intestinal inflammation.

Comparative anti-diabetic, anti-inflammatory, and chromatographic screening of bioactive compounds in selected medicinal plants: extraction system effects

Comparative anti-diabetic, anti-inflammatory, and chromatographic screening of bioactive compounds in selected medicinal plants: extraction system effects

The extraction and anti-inflammatory screening of Onosma glomeratum Y. L. Liu

“Zicao” has a long medicinal history and has a variety of pharmacological activities. As the main resource of “zicao” in Tibet, Onosma glomeratum Y. L. Liu (tuan hua dian zi cao), usually used for treating pneumonia in Tibet, has not been reported deeply. In order to determine the main anti-inflammatory active ingredients of Onosma glomeratum Y. L. Liu, in this study, the extracts enriched in naphthoquinones and polysaccharides were optimized prepared form Onosma glomeratum Y. L. Liu by ultrasonic extraction, and reflux extraction, respectively, with Box-Behnken design effect surface method. And their anti-inflammatory abilities were screened on LPS induced A549 cells model, for figuring out the anti-inflammatory active ingredients from Onosma glomeratum Y. L. Liu. The extract enriched naphthoquinone was obtained under following condition: extract with 85% ethanol in a liquid to material ratio of 1:40 g/mL at 30 °C for 30 minutes using ultrasound, leading to the extraction rate of total naphthoquinone as 0.98 ± 0.017%; the extract enriched polysaccharides was prepared as follows: extract 82 minutes at 100 °C with distilled water in a liquid to material ratio of 1:50 g/mL, with extraction rate of polysaccharide as 7.07 ± 0.02%. On the LPS-induced A549 cell model, the polysaccharide extract from Onosma glomeratum Y. L. Liu showed better anti-inflammatory effects than the naphthoquinone extract, indicating the extract enriched in polysaccharides is the anti-inflammatory extract of Onosma glomeratum Y. L. Liu, which could serve as a potential anti-inflammatory extract in medical and food industries in the future.

Pyrazole appended hetero-hybrids: Bioisosteric design, synthesis, in silico and in vitro antibacterial and anti-inflammatory evaluations

In the present investigation, we adopted bioisosteric based design and synthesis of pyrazole appended "New Molecular Hybrids" to develop antibacterial agents that are efficient against multidrug resistant bacteria. Structure of the compounds were well characterized with the aid of spectroscopic and analytical techniques and, the selected derivatives were further confirmed through the single crystal X-ray analysis. Following an in-silico evaluation of the compounds' effectiveness through docking studies and ADMET calculations, we conducted an in vitro antibacterial assessment and found that 6c was the most effective, having an MIC of 5 µg/mL against P. aeruginosa and M. smegmatis, which was superior to standard drug ampicillin (15.6 and 6.25 µg/mL, respectively). SAR studies of compound 6c on protein 1kzn indicate that it has a binding energy of -8.64 kcal mol−1 via various noncovalent interactions. The anti-inflammatory potential screening revealed that, 6b was the most potent with an IC50 of 9.3 µg/mL, which is moderately active in comparison to standard aspirin (5.03 µg/mL). Thus, based on SAR studies, ADMET calculations, and in vitro studies, the new hybrids appear to be promising hits for the antibacterial and anti-inflammatory drug discovery endeavours.

Anti-inflammatory labdane diterpenoids from the aerial parts of Leonurus japonicus

Twenty-two labdane-type diterpenoids, including ten pairs of 15-epimers and a pair of 13,15-epimers, were obtained from the aerial parts of a well-known medicinal plant Leonurus japonicus Houtt. While these epimers were separated by chiral HPLC, their structures were established mainly via spectroscopic methods especially NMR, X-ray crystallography and ECD techniques. Among them, seventeen compounds, encompassing three pairs of solvolysis artefacts likely due to the use of ethanol as extracting solvent, were reported for the first time in the current work. Our preliminary anti-inflammatory screening demonstrated that seven diterpenoids displayed noteworthy inhibitory effect on the NO production in LPS-induced RAW264.7 cells. In addition, the release of pro-inflammatory factors TNF-α, IL-1β and IL-6, as well as the expression of iNOS and COX-2 proteins, was also suppressed by the unreported 15,16-epoxy-6β-hydroxy-15α-methoxy-7,16-dioxolabd-8,13-diene. Further investigation into the preliminary anti-inflammatory mechanism of this compound indicated that it could block the activation of NF-κB signaling pathway.

Bioactivity-Guided High Performance Counter-Current Chromatography and Following Semi-Preparative Liquid Chromatography Method for Rapid Isolation of Anti-Inflammatory Lignins from Dai Medicinal Plant, Zanthoxylum acanthopodium var. timbor.

The development of Dai medicine is relatively slow, and Zanthoxylum has great economic and medicinal value. It is still difficult to obtain medicinal components from the low-polarity parts of Zanthoxylum belonging to Dai medicine. In this study, we introduced one simple and quick strategy of separating target compounds from the barks of Z. acanthopodium var. timbor by high-performance countercurrent chromatography (HPCCC) with an off-line anti-inflammatory activity screening mode. The development of this strategy was based on the TLC-based generally useful estimation of solvent systems (GUESS) method and HPCCC in combination. This paper presented a rapid method for obtaining target anti-inflammatory compounds. Three lignins were enriched by HPCCC with an off-line inhibition mode of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 macrophage cells, using petroleum ether-ethyl acetate-methanol-water (3:2:3:2) as the solvent system. The results showed that this method was simple and practical and could be applied to trace the anti-inflammatory components of the low-polarity part in Dai medicine.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this “two-cell” (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Chemical constituents from the twigs and leaves of Picrasma quassioides

Two new compounds, including a norsesquiterpenoid, annuionone H (1), and a quassinoid, picraqualide G (2), along with eleven known compounds (3–13), were isolated from the twigs and leaves of Picrasma quassioides. Comprehensive spectroscopic analyses and NMR calculation with DP4+ analysis were used to identify their structures. Moreover, of all these compounds, compound 4 showed a week inhibition rate in the anti-inflammatory screening results against mouse macrophage J774A.1 cell.

Anti-inflammatory activity and HPTLC phytochemical screening of Hibiscus sabdariffa leaves

Anti-inflammatory activity and HPTLC phytochemical screening of Hibiscus sabdariffa leaves

Synthesis and anti-inflammatory activity of S-oxides of pyridinyloxy substituted imidazo[2,1-b][1,3]thiazines

Here derivatives of imidazo[2,1-b][1,3]thiazines are attractive objects for organic and medicinal chemists. In the present work chemoselective conditions for oxidation of the sulfur atom in the 6-(2-pyridinyloxy)substituted (benzo)imidazo[2,1-b][1,3]thiazines to the corresponding sulfoxides were proposed and their synthesis was performed. Synthesized sulfoxides exist in the diastereomeric mixture and individual diastereomers 2a-e and 3a-e were obtained using a chromatographic technique. The structure of compounds 2a-e and 3a-e were characterized using 1H, 13C NMR, LC-MS spectra, and X-ray analysis for derivative 2b. The anti-inflammatory activity screening in vivo was performed using the carrageenan model of inflammatory paw edema in white rats for all the diastereomeric mixtures and individual diastereomers. Diastereomer 2c possessed an anti-inflammatory effect with an inflammation inhibition index of 46.1% which was equal to the activity of the reference drug diclofenac sodium.

Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with myeloid differentiation factor 2 (MD2).

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a challenging clinical syndrome that leads to various respiratory sequelae and even high mortality in patients with severe disease. The novel pharmacological strategies and therapeutic drugs are urgently needed. Natural products have played a fundamental role and provided an abundant pool in drug discovery. A compound library containing 160 natural products was used to screen potential anti-inflammatory compounds. Mice with LPS-induced ALI was then used to verify the preventive and therapeutic effects of the selected compounds. Licochalcone A was discovered from the anti-inflammatory screening of natural products in macrophages. A qPCR array validated the inflammation-regulatory effects of licochalcone A and indicated that the potential targets of licochalcone A may be the upstream proteins in LPS pro-inflammatory signalling. Further studies showed that licochalcone A directly binds to myeloid differentiation factor 2 (MD2), an assistant protein of toll-like receptor 4 (TLR4), to block both LPS-induced TRIF- and MYD88-dependent pathways. LEU61 and PHE151 in MD2 protein are the two key residues that contribute to the binding of MD2 to licochalcone A. In vivo, licochalcone A treatment alleviated ALI in LPS-challenged mice through significantly reducing immunocyte infiltration, suppressing activation of TLR4 pathway and inflammatory cytokine induction. In summary, our study identified MD2 as a direct target of licochalcone A for its anti-inflammatory activity and suggested that licochalcone A might serve as a novel MD2 inhibitor and a potential drug for developing ALI/ARDS therapy.

Anti-Inflammatory Screening of Ulmus pumila L ethanolic extract

Deciduous trees of Ulmus species were reported to exhibit antibiotic, antifungal, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, antiangiogenic, and antiviral effects that rich in flavonoids. In this study, phytochemical analysis and pharmacological activities of Ulmus pumila L were studied. The upper parts of Ulmus pumila L plants were grinded and extracted in 80% ethanol with a ratio of 1:10, infusing by maceration method. The total crude extract was fractioned into a group of solvents with increasing polarity: hexane, chloroform, ethyl acetate, and n-butanol. The results of the toxicity test showed the safety of the oral ingestion and treatment with ethanolic and ethyl-acetic fractions decreased inflammatory symptoms and exhibited protective effects for carrageenan-induced paw edema. These preliminary findings may support its traditional medicinal use and could be promising candidate with application in the treatment of inflammatory symptoms.

Ulcer Index, Analgesics and Anti inflammatory Screening of Some Arylidene Compounds Derived from Phenyl Hydrazine and Aromatic Aldehydes

Arylidene derivatives were synthesized from phenyl hydrazine and series of different aldehydes. Arylidene compounds are important classes of N-containing fused heterocycles widely used as key building blocks for pharmaceutical agents due to a wide range of biological activities that include anti-inflammatory and antitumor properties [1]. Arylidene derivatives were furnished by the fusion of benzene ring with different aldehydes via hydrazine moiety in the presence of glacial acetic acid. These derivatives were characterized by TLC, melting points, Infrared Red, Nuclear Magnetic Resonance and Mass Spectroscopy. Finally, these synthetized derivatives were tested for analgesic activity using hot plate test method, anti-inflammatory activity using rat paw oedema and ulcer index test.