Significant Anti-inflammatory Activity Research Articles

Anti- Inflammatory Activities Of The Methanol Leaf Extract And Fractions Of Elaesis Guineensis In In-Vivo Animals

Abstract Objective Objective of this paper is to investigate the preliminary anti-inflammatory property of the leaves and its fractions of Elaesis guineensis using egg induced albumin and formaldehyde induced arthritis models in rats. Method Egg albumin induced inflammation was induced by sub-plantar injection of 0.1 ml of fresh undiluted egg albumin. The volume of distilled water displaced by the treated paw was measured at 0.5,1, 2, 3, 4, 5, and 6 hours after induction of inflammation. Formaldehyde-induced arthritis was induced after 30 min by sub-plantar injection of 0.1 ml of 2.5% formaldehyde solution and was repeated on day 3. Arthritis was assessed by measuring the volume of distilled water displaced by the paw before induction of arthritis and once every day for ten days, starting from day one, after induction of arthritis. Results The acute toxicity test revealed that the plant extract was safe even at 5000 mg/kg dose level. The methanol extract (ME) showed a dose-dependent inhibition of egg albumin-induced acute inflammation that peaked at the dose of 200 mg/kg, while the fractions of the extract showed that the hexane and ethyl acetate fractions had the highest activity during the experiment. Similarly, the crude extract of the formaldehyde induced arthritis showed a dose-dependent inhibition making the 200 mg/kg the most active dose level. Additionally, it was observed that among the fractions of the extract the hexane fraction (HF) showed the most significant inhibitory activity when compared to other fractions Conclusion this study establishes that the methanol leaf extract and fractions ofElaesis guineensis possess significant anti-inflammatory activity

Carboxylic Acids as Activators of NRF2: Antioxidant and Antiinflammatory Effects

Abstract: The complex interaction between carboxylic acids and molecular signaling pathways, particularly the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, is of growing interest in medicinal chemistry due to its potential therapeutic benefits. Carboxylic acids, which are widely distributed in nature, are versatile regulators of cellular responses due to their ability to interact with multiple signaling pathways, especially those involved in combating oxidative stress and inflammation. Several carboxylic acids exhibit significant antioxidant and anti-inflammatory activities. They have been identified as potential activators of the NRF2 transcription factor, a key regulator of endogenous antioxidants that maintains cellular redox homeostasis and modulates the production of several antioxidant proteins and detoxifying enzymes. The potential effects of carboxylic acid-NRF2 crosstalk are exhibited in a variety of physiological processes, such as attenuation of oxidative stress and inflammation, detoxification of xenobiotics, and modulation of the immune system. The molecular docking of some carboxylic acids with NRF2 protein showed that their binding affinities were comparable to dimethyl fumarate, a reference drug. The current review explores the evolving landscape of carboxylic acid-NRF2 interactions and their mechanisms of action, highlighting the possible impact of their antioxidant and anti-inflammatory effects on inflammation and oxidative stress-mediated diseases. The natural and synthetic sources of NRF2-activating carboxylic acids and the role of their chemical and physical properties in influencing NRF2-inducing activities were discussed. Their potential challenges as future drugs and clinical trial prospects were also highlighted. Carboxylic acid-NRF2 interactions offer potential for developing therapies that will attenuate oxidative stress and inflammation.

Synthesis, Crystal Structure, Spectroscopic Characterization, In Vitro and In Silico Molecular Docking Studies of Benzyl Tetrazole-N-Isobutyl Acetamide Hybrid

Background: Tetrazole-based compounds are of significant interest due to their potential pharmacological applications. The current study focuses on the synthesis and analysis of such a compound. Objective: This research aims to synthesize the title compound N-(3-methyl-1-phenyl-2-(1Htetrazol- 1-yl) butyl) acetamide, analyze its crystal structure, perform computational studies, and evaluate its potential pharmacological activities and it’s in silico and in vitro supports, specifically antidiabetic and anti-inflammatory properties. Methods: The title compound, C14H19N5O, was synthesized, and its crystal structure was confirmed using single-crystal X-ray diffraction analysis by default parameters. Density Functional Theory (DFT) calculations were performed using the Gaussian 09W software package with the B3LYP/6-311++G (d,p) method to optimize the compound's structure and calculate its HOMOLUMO energy gap, Molecular Electrostatic Potential (MEP), and Mulliken charge distribution. In vitro, antidiabetic and anti-inflammatory activities were assessed and compared with standard drugs by using reported protocols. Additionally, molecular docking studies were conducted with enzymes related to diabetes and inflammation with default parameters, and Auto-Dock 4.2 software was used. Results: The X-ray diffraction analysis confirmed the crystal structure, and the Density Functional Theory (DFT) calculations provided insights into the molecular properties of the compound. Molecular docking experiments with relevant enzymes further supported the significant antidiabetic and anti-inflammatory activities demonstrated in the in vitro tests. Conclusion: The synthesized tetrazole-based compound exhibits promising antidiabetic and antiinflammatory activities, supported by both experimental and theoretical studies, suggesting its potential for further pharmacological investigation.

Evaluation of Dermal Wound Healing Potential: Phytochemical Characterization, Anti-inflammatory, Antioxidant, and Antimicrobial Activities of Euphorbia guyoniana Boiss. & Reut. Latex.

This study investigates the wound-healing potential of Euphorbia guyoniana latex (EGL) in male Wistar rats, along with its biochemical composition and biological activities. Phytochemical analysis identified moderate levels of phenolics, flavonoids, and tannins, with HPLC revealing five phenolic compounds. EGL demonstrated strong antioxidant activity in DPPH assays, surpassing ascorbic acid in protecting red blood cells. Its performance in the ß-carotene-linoleic acid assay was robust, though its FRAP assay results were weaker. EGL also exhibited significant anti-inflammatory activity, comparable to Acetylsalicylic acid, and showed antibacterial effects against Listeria innocua. In Vivo, EGL-infused ointments accelerated wound healing, reducing epithelialization periods to 12-16 days, with a higher wound contraction rate compared to controls. The study concludes that EGL, rich in bioactive compounds, holds potential as a promising natural agent for wound healing, owing to its potent antioxidant, anti-inflammatory, and antibacterial properties.

Development of optimized standardized extracts of Echinodorus macrophyllus for arthritis management

Ethnopharmacological relevanceEchinodorus macrophyllus is a medicinal plant traditionally used in Brazil to treat rheumatic diseases. It is listed as a priority species for the development of herbal preparations for the Brazilian Unified Health System (SUS). Previous studies have demonstrated the anti-inflammatory and antiedematogenic properties of extracts and fractions from this species, but these preparations were neither standardized nor optimized for anti-arthritis effects. Aim of studyThis study aimed to investigate the anti-inflammatory and antiarthritic effects of various standardized extracts from the aerial parts of E. macrophyllus and to outline their mechanisms of action. The goal was to define an extract suitable for future scientific validation and clinical use. Material and methodsExtracts from the aerial parts of E. macrophyllus were prepared through percolation with 96°GL ethanol (EtOH) and hydroethanolic solutions at 90%, 70%, and 50% (v/v). They were standardized based on the contents of six chemical markers quantified by UPLC-DAD. Mice with acute or chronic antigen-induced arthritis (AIA) were treated with the extracts orally. The effects were evaluated by counting total and differential inflammatory cells, measuring cytokines by ELISA, and by histological analysis with toluidine blue staining. The mechanism of selected extracts was investigated in LPS-stimulated murine chondrocytes. ResultsAll extracts, except for the 90% EtOH extract, exhibited significant anti-inflammatory activity in acute AIA, reducing the migration of total inflammatory cells, neutrophils, and monocytes to the intra-articular cavity. In chronic AIA, both the 96°GL EtOH and 70% EtOH extracts markedly reduced the migration of total inflammatory cells, neutrophils, and monocytes to the intra-articular cavity, decreased IL-1β and CXCL1 levels in the periarticular tissue, and diminished proteoglycan loss in the articular cartilage. Both extracts reduced IL-6 release and MMP-3 expression in LPS-stimulated chondrocytes. The 70% EtOH and 50% EtOH extracts showed heightened activity and higher levels of chemical markers, notably cinnamoyl-tartaric acid derivatives. ConclusionsThe standardized 70% EtOH and 50% EtOH extracts from the aerial parts of E. macrophyllus, which contain higher levels of chemical markers, exhibit potent anti-inflammatory activity and reduce proteoglycan degradation. These extracts are potentially useful for developing herbal preparations to manage arthritic conditions and should be prioritized for further studies.

Evaluation of antioxidant, anti-inflammatory and cytotoxic potential of phytochemicals from Gymnostachyum febrifugum-an in vitro study

Gymnostachyum febrifugum an ethnomedicinal plant of Acanthaceae family is used to treat fever, ulcer and metrorrhagia. The current study aimed to determine the antioxidant, anti-inflammatory and cytotoxic potential of phytochemicals from methanolic leaf and root extracts of G. febrifugum. In addition, a preliminary phytochemical analysis was carried out using thin layer chromatography (TLC) and liquid chromatography-mass spectrometry (LC-MS). The study revealed significant antioxidant and anti-inflammatory activities of methanolic extracts of G. febrifugum roots compared to that of leaves. Also, a moderate in vitro cytotoxic effect of the root methanolic extracts was observed against human lung cancer cells. LC-MS analysis of the methanolic extract of root revealed the presence of 11 phytochemicals belonging to classes of alkaloids, flavonoids, terpenoids and sugars, of which esculin, 6,7,10-trihydroxy-8-octadecenoic acid, piperlongumine, ardisiacrispin B and berbamine were detected in high abundance. Probably, these phytochemicals were responsible for the antioxidant, anti-inflammatory and cytotoxic potential of G. febrifugum. However further research on isolation and identification of active compounds is necessary to confirm these results.

Application of Network Pharmacology, Molecular Docking, and In Vitro Experimental Evaluation to Decipher the Anti-Inflammatory Mechanisms of Cirsium japonicum

Cirsium japonicum, a traditional herb, exhibits significant anti-inflammatory activity. However, the main components and potential mechanisms of C. japonicum remain unclear. The aim of this study is to investigate the anti-inflammatory mechanism of Cirsium japonicum through network pharmacology and cellular experiments. The effective components of and potential targets for the anti-inflammatory activity of C. japonicum were identified using a traditional Chinese medicine systematic pharmacology database, the TCMSP analysis platform, and the GeneCards database. The drug–component–target–disease network diagram was constructed using Cytoscape 3.8.0 software, while the protein interaction network diagram was created using the STRING database and Cytoscape 3.8.0 software. Gene ontology (GO) enrichment and KEGG pathway enrichment analysis were carried out using the DAVID database. Molecular docking between key targets and active components was constructed with AutoDock 4.2.6 software to determine the best binding target. The results revealed that 14 active components of C. japonicum targeted 171 anti-inflammatory proteins. GO function enrichment analysis yielded 173 items, while KEGG pathway enrichment analysis identified 48 signaling pathways related to inflammation regulation. Molecular docking showed a strong affinity of sitosterol, stigmasterol, and other components with key targets such as peroxisome proliferator-activated receptor α recombinant protein (PPARA) and cyclooxygenase-2 (PTGS2). Vanillin, one active ingredient of C. japonicum, inhibited the release of lipopolysaccharide (LPS)-induced inflammatory factors in RAW264.7 cells. These findings suggest that C. japonicum may exert its anti-inflammatory effects by modulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal pathway (PI3K-Akt) and apoptin signal pathway, highlighting the multi-component, multi-target, and multi-channel molecular mechanism underlying its anti-inflammatory properties. Finally, the anti-inflammatory effect of vanillin, an effective component of C. japonicum, was verified by cell experiments. This study provides a new understanding of the pharmacological mechanisms of C. japonicum in the treatment of inflammatory conditions.

Anti-inflammatory oxazole-, nitro- and hexahydropyrrolo[2,1-b]oxazole-containing abietane diterpenoid alkaloids from Salvia miltiorrhiza

Nine undescibed abietane diterpenoid alkaloids (DAs), salviamines G‒H (1–2), isosalviamines G‒J (3–6), and miltiorramines A‒C (7–9) were isolated from the roots of Salvia miltiorrhiza. Their chemical structures including absolute configurations were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS), combined with the calculated ECD method and single-crystal X-ray diffraction analysis. Among them, compounds 1–6 are unusual 20-nor- or 19,20-bisnor-abietane DAs with an oxazole ring. Compounds 7–8 are the first examples of DAs with a nitro group isolated from plant sources. Notably, compound 9 possesses a rare hexahydropyrrolo[2,1-b]oxazole unit that is fused in the ring B of the abietane skeleton. Bioactivity assay indicated that compound 3 showed significant anti-inflammatory activity by decreasing the gene expressions of IL-1β, IL-6, and TNF-α in LPS-induced RAW264.7 cells in a dose-dependent manner.

Formulation and characterization of tea tree and jojoba oils nano-emulgel for in-vivo wound healing assessment

Cutaneous wounds are the most common surgical affections among living organisms worldwide, and their healing may be interrupted by several factors. This study aimed to formulate and evaluate the antioxidant, anti-inflammatory, and antimicrobial activity of tea tree and jojoba oils nano-emulsions, additionally, investigating the cytotoxicity of the optimized formula was investigated on normal human lung fibroblast cells (WI-38) by MTT colorimetric assay, additionally its in-vivo wound healing. Nano-emulsions (NEs) were prepared using a high-energy method and characterized by Transmission electron microscopy (TEM), Zeta potential, droplet size, and poly dispersive index (PDI). Nano-emulgel (NEG) was formulated by mixing the standard NE with carbopol® 940. For in-vivo wound healing, thirty adult female albino rats were assigned into control, moist exposed burn ointment (Mebo), and NEG-treated groups. The healing was assessed by analysis of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and histopathology in healed wound tissues. All formulations demonstrated antioxidant, anti-inflammatory, and antimicrobial activity against Bacillus Subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Enterococcus faecalis, and Candida albicans. The CC50 of the optimized formula was 453.82± 3.87 µg/mL, with a mean droplet size of 105.4 nm and a zeta potential of −39.2 ± 2.1 mV. NEG enhanced wound closure compared to Mebo-treated and control groups. Also, MDA significantly decreased and SOD significantly increased in NEG and Mebo-treated groups compared to the control (p ˂ 0.05). TNF-α, and IL-1β significantly decreased in NEG and Mebo-treated compared to the control (p < 0.05). Histopathology revealed reduced inflammatory cell infiltration, rapid epithelization, and increased collagen deposition in NEG-treated wound tissues compared to the control and Mebo-treated wounds. In conclusion, the NEG containing tea tree and jojoba oils demonstrated significant antioxidant, anti-inflammatory, antimicrobial, and wound healing activities.

Evaluation of the in vitro toxicity and anti-inflammatory activity of the methanolic extract of the leaves of Pistacia lentiscus L. harvested from northwestern Algeria.

Medicinal and aromatic plants have been used for thousands of years for their therapeutic properties, to treat various ailments and maintain health. This study was carried out to test the in vitro toxicity and anti-inflammatory activity of the methanolic extract of the leaves of Pistacia lentiscus L., native to the north-western region of Algeria. Toxicity was studied in vitro by the hemolysis test and anti-hemolytic activity on human red blood cells, while anti-inflammatory activity was assessed in vitro by the protein denaturation method. The study of toxicity by hemolysis of red blood cells showed a high rate of hemolysis at a dose of 200 mg/mL, with a hemolytic percentage of around 88.64%, while a high rate of anti-hemolysis was observed at a dose of 25 mg/mL, with an inhibition percentage of around 83.17%. Evaluation of anti-inflammatory activity revealed a high percentage of inhibition of ovalbumin denaturation, reaching 63.53% at the 2000 ug/mL dose, while the lowest percentage was obtained at the 3500 ug\mL concentration with 10.16%. This extract has a toxic substance but does not exceed the toxicity threshold which achieves significant anti-inflammatory activity with depandant doses.

Apodanthera glaziovii (Cucurbitaceae) Shows Strong Anti-Inflammatory Activity in Murine Models of Acute Inflammation.

Background/objectives:Apodanthera glaziovii is an endemic species from the semi-arid Brazilian, which has limited toxicological and pharmacological studies. This species belongs to a well-studied family known for its bioactive compounds used in treating inflammatory. This study aimed to identify secondary metabolites in the stems from A. glaziovii, evaluate toxicity, and investigate the anti-inflammatory potential of the stem hydroalcoholic extract (SHE-Ag). Methods: qualitative and quantitative assays were employed to identify secondary metabolites, along with chromatographic analyses and 1H and 13C NMR. Toxicity was assessed through in vitro hemolytic toxicity, in vivo genotoxicity, and oral acute toxicity tests before the pharmacological assays were conducted. Results: phytochemical screening, HPLC and NMR analyses suggested the presence of saponins of the norcucurbitacin class. The SHE-Ag exhibited no hemolytic activity and no mutagenic potential. However, in vivo toxicity at a dose of 2000 mg/kg revealed hematological and biochemical alterations, while the 500 mg/kg dose was safe. In the anti-inflammatory assays, SHE-Ag at 100 mg/kg reduced paw edema by 55.8%, and leukocyte and neutrophil migration by 62% and 68% in the peritonitis model, respectively; inflammatory cell migration by 70% in the air pouch model, outperforming indomethacin, which showed a 54% reduction. Conclusions: these findings indicate that SHE-Ag is rich in saponins, confirmed through HPLC and 1H and 13C NMR analyses. The SHE-Ag also demonstrated low toxicity. The inflammation models used showed a reduction in inflammation, pro-inflammatory cells, and edema, highlighting the significant anti-inflammatory activity of hydroethanolic extract A. glaziovii stems.

Synthesis and Biological Evaluation of Gastroprotective Polymer Conjugates of Aceclofenac

: Nonsteroidal anti-inflammatory drugs account for a sizeable fraction of the drugs prescribed worldwide. If consumed for a long time, they can cause ulcers and lifethreatening side effects. Since the acidic group present in NSAIDs is mainly responsible for these side effects, the scientists try to synthesize polymer drug conjugates that avoid these side effects but still retain the potency of the parent drug. Macromolecular drug conjugates of aceclofenac were prepared by employing pectin, β cyclodextrin, deacetylated chitin (chitosan) and albumin (egg and bovine serum). The prepared conjugates were characterized and tested for their anti-inflammatory, antinociceptive and antiulcerogenic activity. Further experimentation was undertaken to analyze the behavior of compounds and their stability in hydrolytic conditions. Test compound A1, a pectin conjugate of aceclofenac, exhibited significant antinociceptive and anti-inflammatory activity with a significant decrease in ulcer index (4.45±0.24) as against aceclofenac (8.61±0.40) or vehicle (12.39±0.44) treated group. A novel and safer polymer drug conjugate of aceclofenac has been synthesized and evaluated.

Phenolic Bisabolane Sesquiterpene Derivatives from an Arctic Marine-derived Fungus Aspergillus sydowii MNP-2

Background:: Filamentous fungi in the genus Aspergillus are well known for their important roles in production of bioactive secondary metabolites with diversely chemical structures and potential application in pharmaceutical industry. Objective:: The present study aimed to investigate the phenolic bisabolane sesquiterpene (PBS) derivatives from an Arctic marine-derived fungus Aspergillus sydowii MNP-2. Methods:: In this study, antimicrobial activities were carried out according to the broth microdilution assay, nitric oxide (NO) production in mouse macrophages (RAW264.7) and BV2 microglial cells was used to detect the inhibitory effect of compounds in inflammatory reactions, and in vitro inhibitory cell proliferation activity was determined by the cell counting kit-8 (CCK-8) assay. Results:: In this work, chemical investigation of an Arctic marine-derived strain A. sydowii MNP-2 led to the isolation of 11 PBSs (1-11) using various chromatographic methods. Their chemical structures were unambiguously determined by 1H NMR spectroscopy and mass spectrometry analyses as well as comparison with literature data. It is noteworthy that compounds 1, 7 and 11 were firstly obtained from A. sydowii. Antimicrobial assay showed that these chemicals had no potent inhibitory effect on Staphylococcus aureus, Escherichia coli, and Candida albicans with MIC values &gt; 16 μg/mL. Additionally, the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)- induced inflammation in mouse macrophages (RAW264.7) and BV2 microglial cells were all below 10% for compounds 4-6 and 8, indicating almost negligible anti-inflammatory efficacy. Among the tested compounds 4-6 and 8 for tumor-cell proliferation inhibition activities, compound 5 demonstrated the strongest inhibitory effect against human acute promyelocytic leukemia cells (HL-6) with a 44.76% inhibition rate. Conclusion:: In the present study, 11 PBS derivatives were purified and characterized from the solidand liquid-state fermentations of the Arctic marine-derived fungus A. sydowii MNP-2. Unfortunately, none of these metabolites had significant antimicrobial, anti-inflammatory, or tumor-cell proliferation inhibition activities.

Novel Synthesized Benzophenone Thiazole Hybrids Exhibited ExVivo and In Silico Anti-Inflammatory Activity.

Novel benzophenone-thiazole hybrids with different substituents were synthesized and evaluated for anti-inflammatory activity using an exvivo human whole-blood assay. All hybrids (3c and 5a-h) showed significant anti-inflammatory activity via prostaglandin E2 (PGE2) release inhibition. Moreover, 5c (82.8% of PGE2 inhibition), 5e (83.1% of PGE2 inhibition), and 5h (82.1% of PGE2 inhibition) were comparable to the reference drugs. Molecular docking revealed potential preferable binding to the active sites of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes. This study provides the first evidence that benzophenone-thiazole hybrids may also dock in mPGES-1, a new attractive anti-inflammatory drug target, besides providing promising exvivo anti-inflammatory activity. Thus, the novel hybrids are promising anti-inflammatory lead compounds and highlight the significance of optimal substituent selection in the design of potent PGE2 inhibitors.

Almond polysaccharides inhibit DSS-induced inflammatory response in ulcerative colitis mice through NF-κB pathway

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic recurrent inflammatory disease of the colon. Our previous findings demonstrated that almond polysaccharide (AP-1) exhibits significant anti-inflammatory activity in vitro. Therefore, this study aimed to explore the ameliorative effect of AP-1 on dextrose sodium sulfate (DSS)-induced UC mice and to elucidate its possible mechanism of action. By observing changes in body weight, fecal viscosity, stool blood, disease activity index, and colon length, we found that AP-1 attenuated inflammation. It inhibited TNF-α, IL-1β, and IL-6 while boosting anti-inflammatory IL-10 levels. Histomorphologically, AP-1 protected against DSS-induced colonic tissue damage by reducing inflammatory cell infiltration and mucosal injury. It also lowered myeloperoxidase (MPO) and NO while increasing total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in colonic tissues. Moreover, using the Western blot technique, AP-1 was shown to inhibit the phosphorylation of p65 and IκB-α proteins in the NF-κB/iNOS/COX2 signaling pathway and down-regulate the expression of inflammation-associated proteins COX2 and iNOS, thus slowing down and ameliorating inflammatory processes. Therefore, the safe and effective beneficial effects of AP-1 make it a promising therapeutic strategy for relieving IBD, especially UC.

Investigation of Antioxidant Potential of Black Beans Due to Phytochemical and Globulin Content for Nutraceutical Application

The study aims to elucidate the antioxidant and anti-inflammatory properties of black beans and identify the key contributors within the beans. Black beans boast high protein and phytochemical content, suggesting potential antioxidant activity. This work delves into this possibility, focusing on the role of globulins (a protein fraction) and various phytochemicals in black bean’s bioactivity. Globulins were isolated from black beans by salt precipitation. Ethanolic and aqueous extracts were prepared, followed by phytochemical screening for phenolics, flavonoids, alkaloids, etc. Quantification of phenolics and flavonoids was performed by colorimetric assays. SDS-PAGE and mass spectrometry identified the isolated globulin. Ferric reducing potential and total antioxidant capacity tests assessed antioxidant capacity, while erythrocyte membrane stabilisation inhibition evaluated anti-inflammatory potential. Black beans exhibited a diverse range of phytochemicals. The ethanolic extract displayed the highest flavonoid content (11.18±0.11mg QE/gram extract), while the aqueous extract was richest in phenolics (0.71±0.14 mg GAE/gram extract). The aqueous extract displayed the strongest antioxidant activity (2.87 ± 0.98 mg AAE/gram extract), followed by the globulin fraction (1.23± 0.43 mg AAE/gram extract). The ethanolic extract demonstrated superior anti-inflammatory activity. Mass spectrometry identified globulin as a 68.7 kDa legumin protein from Phaseolus vulgaris. Black beans display significant antioxidant and anti-inflammatory activity due to globulins and diverse phytochemicals. By informing dietary practices and facilitating the development of nutraceutical interventions, this work has the potential to contribute to a healthier population.

Senna alata: Phytochemistry, Antioxidant, Thrombolytic, Anti-inflammatory, Cytotoxicity, Antibacterial activity, and GC-MS analysis

Objective: Nepal's medicinal herbs are rich in cultural importance and have several uses. Senna alata, a plant belonging to the Leguminosae family, is prized for its aesthetic and therapeutic qualities. The goal of the study was to extract Senna alata leaves using several solvent macerations. Methods: The study aims to evaluate the phytochemistry, total phenolic and flavonoid levels, antioxidant qualities in vitro, anti-inflammatory effects, cytotoxicity, anti-thrombolytic potential, and antibacterial activity, a variety of methodologies were employed. Results: The extractive values of Senna alata were determined as 1.58%, 0.78%, and 5.92% in hexane, ethyl acetate, and methanol, respectively. GC-MS analysis revealed major compounds such as 3-Methylmannoside, Neophytadiene, Campesterol, and Vitamin E in the leaf extract. Qualitative phytochemical screening confirmed the presence of tannins, carbohydrates, flavonoids, cardiac glycosides, glycosides, and saponins in the methanol extract. The total phenolic and flavonoid contents were 46.36±4.5 mg GAE/g and 480.4±3.055 QE/g of dried extract, respectively. The extract exhibited significant antioxidant and anti-inflammatory activities, with IC50 values of 29.81 and 9.93, respectively. Additionally, it demonstrated cytotoxic activity with an LC50 value of 767.85 in the brine shrimp bioassay. In terms of thrombolytic activity, the extract showed clot lysis percentages of 7.89% and 10.13% at concentrations of 10 mg/ml and 25 mg/ml, respectively. Conclusion: The methanolic extract of Senna alata leaves displayed therapeutic potential, including antioxidant, anti-inflammatory, cytotoxic, thrombolytic, and antibacterial effects. The presence of several bioactive compounds, as confirmed by GC-MS analysis, further supports the plant's potential for therapeutic use.

Comparison of the difference in the anti-inflammatory activity of two different color types of Farfarae Flos based on in vitro, in vivo experiments and untargeted metabolomics.

Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored. This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms. Our findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos. This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos.

Design, Synthesis, Anti-Cancer, Anti-Inflammatory and In Silico Studies of 3-Substituted-2-Oxindole Derivatives.

This study focuses on the design and synthesis of 3-substituted-2-oxindole derivatives aimed at developing dual-active molecules with anti-cancer and anti-inflammatory properties. The molecules were designed with diverse structural and functional features while adhering to Lipinski, Veber, and Leeson criteria. Physicochemical properties were assessed using SWISSADME to ensure drug-likeness and favourable pharmacokinetics. Multistep synthetic procedures were employed for molecule synthesis. In vitro evaluations confirmed the dual activity of the derivatives, with specific emphasis on the significance of dialkyl aminomethyl substitutions for potency against various cell lines. 4 a exhibited GI50 value 3.00E-05 against MDA-MB-231, 4 b has shown GI50 value 2E-05 against MDA-MB-231, 4 c has shown GI50 value 6E-05 against VERO, 4 d has shown GI50 value 8E-05 each against both the MDA-MB-231 and MCF-7 and 4 e has shown GI50 values 2E-05 and 5E-05 each against both the MCF-7 and VERO. The analysis indicates that compounds 3 c (71.19 %), 3 e (66.84 %), and 3 g (63.04 %) exhibited significant anti-inflammatory activity. Additionally, in silico binding free energy analysis and interaction studies revealed significant correlations between in vitro and computational data, identifying compounds 4 d, 4 e, 3 b, 3 i, and 3 e as promising candidates. Key residues such as Glu917, Cys919, Lys920, Glu850, Lys838, and Asp1046 were found to play critical roles in ligand binding and kinase inhibition, providing valuable insights for designing potent VEGFR2 inhibitors. The Quantum Mechanics-based Independent Gradient Model analysis further highlighted the electronic interaction landscape, showing larger attractive peaks and higher electron density gradients for compounds 4 d and 4 e compared to Sunitinib, suggesting stronger and more diverse attractive forces. These findings support the potential of these compounds for further development and optimization in anticancer drug design.

Curcumol derivatives exhibit ameliorating effects on lipopolysaccharide-induced acute lung injury: Synthesis, biological evaluation, structure–activity relationship and action mechanism

Acute lung injury (ALI) is an intricate clinical disease marked by high mortality and a sudden start. Currently, although there are no specific therapeutics for ALI, the administration of anti-inflammatory drugs is a promising treatment strategy. Curcumol, a terpenoid natural product, has demonstrated significant anti-inflammatory activity. Herein, we designed and synthesised 42 curcumol derivatives using curcumol as the core scaffold. These derivatives underwent in vitro screening for anti-inflammatory activity, and their structure–activity relationship was assessed. Among them, derivative 2 exhibited potent anti-inflammatory potential, inhibiting the expression of inflammatory markers at the nanomolar level. In addition, its water solubility was considerably improved, thereby laying the foundation for enhanced druggability. Derivative 2 also ameliorated lipopolysaccharide (LPS)-induced ALI and reduced pulmonary inflammation at a dose of 5 mg/kg. Proteomics analysis revealed that the anti-inflammatory effect of this compound primarily involved the mTOR signalling pathway. Furthermore, molecular docking and cellular thermal shift assays indicated that GSK3β is a critical target of action of derivative 2, as verified via western blotting. These findings suggest that derivative 2 can be a lead therapeutic compound for ALI, with GSK3β emerging as a promising novel target for the development of specific anti-ALI drugs.