Carrageenan-induced Paw Edema In Mice Research Articles

Synthesis and anti-inflammatory activity of benzimidazole derivatives; an in vitro, in vivo and in silico approach

Many non-steroidal anti-inflammatory drugs (NSAIDs) concurrently inhibit both COX-1 and COX-2, with a preference for specifically targeting COX-2 due to its significant involvement in various pathologies. In addition to COX enzymes, several other targets, including Aldose reductase, Aldo-ketoreductase family 1-member C2, and Phospholipase A2, have been identified as contributors to inflammation and a myriad of other diseases.In this context, a series of 2-substituted benzimidazole derivatives was synthesized and assessed for their anti-inflammatory potential through both in vitro and in vivo assays. Molecular docking studies were conducted to elucidate the mechanism of action of these compounds against COX enzymes and other therapeutic targets associated with NSAIDs, such as Aldose reductase, AIKRC, and Phospholipase A2.Among the synthesized compounds, B2, B4, B7, and B8 demonstrated IC50 values lower than the standard ibuprofen, as determined by the Luminol-enhanced chemiluminescence assay. Validation of these findings was achieved through an in vivo carrageenan-induced mice paw edema model, confirming a comparable anti-inflammatory effect to diclofenac sodium observed in vitro. Notably, these compounds exhibited significant binding affinity with all therapeutic targets investigated in this study.These results suggest that the newly synthesized derivatives possess noteworthy anti-inflammatory potential, warranting further exploration for the development of novel multi-targeting inhibitors.

Pharmacological screening of Anti-inflammatory and Analgesic activity of Apigenin in Mice Model

Introduction: Apigenin is a flavonoid found in many fruits and vegetables as well as in Chinese medicinal herbs. This study aimed to assess the anti-inflammatory and analgesic effects of Apigenin. Materials and Methods: Carrageenan-induced mouse paw edema was used to assess anti-inflammatory activityand Eddy's hot plate analgesiometer was used to assess analgesic activity. Results and Discussion: Apigenin at dosages of 25 mg/kg and 50mg/kg body weight significantly reduced Carrageenan-induced paw edema by 41.21% (3–9 h) and 61.4% (3–9 h), respectively. Apigenin 25mg/kg and 50mg/kg body weight produced significant dose-response analgesic activity in the hot plate test. Conclusion: The findings in this study suggest that Apigenin possesses anti-inflammatory and analgesic activities in a dose dependent manner.

Analgesic, Anti-Inflammatory, and Chondroprotective Activities of Siraitia grosvenorii Residual Extract.

Inflammation is crucial to osteoarthritis (OA) pathogenesis. The aim of this study was to evaluate Siraitia grosvenorii residue extract (NHGRE) obtained by extracting S. grosvenorii fruits with water as a potential food supplement for treating arthritis based on its analgesic, anti-inflammatory, and chondroprotective effects and the remaining residue with 70% ethanol. We observed the analgesic activity of NHGRE based on the acetic acid-induced writhing response in mice, examined its anti-inflammatory efficacy against carrageenan-induced paw oedema in mice, and investigated its effect on inflammatory cytokine expression in interleukin (IL)-1β-induced SW1353 cells. Furthermore, we determined its effects on cartilage protection in interleukin-1β (IL-1β)-treated SW1353 cells. NHGRE at 200 mg/kg significantly reduced the acetic acid-induced writhing response and prevented oedema formation in the carrageenan-induced paw oedema model. In IL-1β-induced SW1353 cells, NHGRE at 400 µg/mL reduced the expression of inflammation mediators such as tumour necrosis factor (TNF)-α (55.3%), IL-6 (35.4%), and prostaglandin E2 (PGE2) (36.9%) and down-regulated the expression of matrix metalloproteinase (MMP)-1 (38.6%), MMP-3 (29.3%), and MMP-13 (44.8%). Additionally, it restored degraded collagen II levels in chondrocytes. NHGRE plays a protective role in chondrocytes by regulating Nuclear factor kappa B (NF-κB) activation. Overall, NHGRE may be a useful therapeutic agent for OA by controlling pain, oedema formation, and inflammation-related mechanisms.

Evaluation of In-vivo Anti-inflammatory activity of methyl 2-(5-butyl-6-thioxo-1, 3, 5-thiadiazinan-3yl), butanoate

Inflammation is the body's way of fending off damage. Nonetheless, continuous and increasing inflammation may lead to the development of some chronic illnesses. It is still needed to evaluate new and safe anti-inflammatory therapies because existing medications have major side effects. Objective: To examine a novel compound's anti-inflammatory properties of methyl 2-(5-butyl-6-thioxo-1, 3, 5-thiadiazinan-3yl), butanoate (MBTTB) in albino mice models. Method: To test the anti-inflammatory effects in vivo, carrageenan-induced paw edema in albino mice of both sexes was utilized, and inflammation was measured by using Digital Plethysmometer. After extraction of carrageenan induced paw edematous, tissue level of inflammatory mediators like TNF-α, IL-1β, NF-ĸβ, and cox2 was ascertained by Western Blot analysis. Result: Based on in-vivo anti-inflammatory effects, compound MBTTB was shown to exhibit a maximum percentage inhibition of 16.7% after 1 hour, which is comparable to the standard drugs 12.8%. Following three hours, compound MBTTB showed the highest percentage inhibition of 23.2%, while the standard was 14.5%. Compound MBTTB showed the highest percentage inhibition after five hours (26.2 %), while the standard was 15.4%. The expression of many mediators' proteins, including TNF-α, IL-1β, NF-ĸβ, and COX-2, was ascertained. The computational analysis was carried out to forecast the level of decline of various mediators, including Tumor Necrosis Factor-α, (TNF) Interleukin-1β, NF-ĸβ, and COX-2. Conclusion: When considered as a whole, our current research indicates that MBTTB is a viable option for preventing inflammation in mice that has been caused by carrageenan in edematous paw.

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.

Phytochemical analysis and immunomodulatory activities in vitro and in vivo of Aframomum melegueta K Schum seed extracts.

Aframomum melegueta K Schum (A. melegueta), an herbaceous plant renowned for its medicinal seeds, was investigated for its potential immunomodulatory effects in vitro and in vivo using ethanolic and methanolic extracts. The immunomodulatory effect was evaluated by measuring antibody titers using the agglutination technique, while anti-inflammatory activity was assessed in a carrageenan-induced mouse paw edema model. In vitro immunomodulatory activity was measured by lysozyme release from neutrophils. Additionally, white blood cell counts were analyzed post-extracts treatment. The MTT assay was employed to determine cytotoxicity, and the biochemical parameters of liver toxicity were evaluated. Remarkably, both extracts exhibited a dose-dependent reduction in paw edema (p < 0.001), with the most significant reduction observed at 1g/kg (78.13 and 74.27% for ethanolic and methanolic extracts, respectively). Neutrophil degranulation was significantly inhibited in a dose-dependent manner (p < 0.003), reaching maximal inhibition at 100μg/mg (60.78 and 39.7% for ethanolic and methanolic extracts, respectively). In comparison to the control group, both antibody production and white blood cell counts were reduced. Neither of the extracts showcased any cytotoxicity or toxicity. These findings suggest that A. melegueta extracts exhibit immunosuppressive and anti-inflammatory activities due to the presence of various biomolecules.

Discovery of dibenzyl amide derivatives as novel CXCR4 modulators against inflammatory bowel disease

The CXCR4/CXCL12 chemokine axis demonstrates significant potential in the treatment of inflammatory bowel disease (IBD) due to its crucial roles in inflammatory and immune responses. Modulating the CXCR4/CXCL12 pathway can be an effective therapeutic approach to ameliorate the inflammatory state of IBD. In this study, a novel series of meta-dibenzyl amide derivatives were designed and synthesized based on the lead compound AMD3100 and its structurally modified derivatives. Both in vitro and in vivo assays conclusively established that these compounds exhibited potent CXCR4 antagonism and anti-inflammatory activity. Compound 5t demonstrated superior inhibitory rates of binding affinity and chemotaxis of CXCR4+ cells compared to AMD3100. Furthermore, compound 5t notably reduced swelling volume and tissue thickness in the carrageenan-induced mouse paw edema model. Most importantly, in the dextran sodium sulfate (DSS)-induced colitis model, compound 5t significantly mitigated colonic inflammation on both macroscopic and microscopic levels, while suppressing the expression of inflammatory factors and myeloperoxidase (MPO). These findings unequivocally establish the immense potential of compound 5t in the treatment of IBD.

Searching for Novel Sources of Hydrogen Sulfide Donors: Chemical Profiling of Polycarpa aurata Extract and Evaluation of the Anti-Inflammatory Effects.

Hydrogen sulfide (H2S) is a signaling molecule endogenously produced within mammals' cells that plays an important role in inflammation, exerting anti-inflammatory effects. In this view, the research has shown a growing interest in identifying natural H2S donors. Herein, for the first time, the potential of marine extract as a source of H2S-releasing agents has been explored. Different fractions obtained by the Indonesian ascidian Polycarpa aurata were evaluated for their ability to release H2S in solution. The main components of the most active fraction were then characterized by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and NMR spectroscopy. The ability of this fraction to release H2S was evaluated in a cell-free assay and J774 macrophages by a fluorimetric method, and its anti-inflammatory activity was evaluated in vitro and in vivo by using carrageenan-induced mouse paw edema. The anti-inflammatory effects were assessed by inhibiting the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and interleukin-6 (IL-6), coupled with a reduction in nitric oxide (NO) and IL-6 levels. Thus, this study defines the first example of a marine source able to inhibit inflammatory responses in vivo through the release of H2S.

Radical Scavenging, Anti-Inflammatory, and Hepatoprotective Activities of Pentacyclic Triterpene isolated from Rosa webbiana.

Rosa webbiana (RW) Wall Ex. Royle is used in traditional medicine in Pakistan for the treatment of several diseases including jaundice. To date, only neuroprotective potential of the plant has been evaluated. The current study was designed to isolate bioactive compound(s) and investigate its possible radical scavenging, anti-inflammatory and hepatoprotective activities. Column chromatography was done to isolate compounds from the chloroform fraction of RW. The compound was characterized by mass spectrometry, 1H-NMR, and 2D-NMR spectroscopy. Radical scavenging activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) assays, while anti-inflammatory potential was evaluated via xylene-induced ear edema and carrageenan-induced paw edema models. For hepatoprotection, CCl4-induced model in mice was used. A triterpene compound (3α, 21β-dihydroxy-olean-12-ene) was isolated from RW fruits (ARW1). The compound exhibited DPPH and H2O2 scavenging activities 61 ± 1.31% and 66 ± 0.48% respectively at 500 μg/ml. ARW1 (at 50 mg/kg) exhibited 62.9 ± 0.15% inhibition of xylene-induced ear edema and 66.6 ± 0.17% carrageenan-induced paw edema in mice. In CCl4-induced hepatotoxic mice, ARW1 significantly countered elevation in alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (T.B), and reduction in total protein (T.P) levels. Liver histomorphological study supported the serum biochemical profile for hepatoprotection. Moreover, ARW1 significantly attenuated the toxic changes in body and liver weight induced by CCl4. The compound ARW1 exhibited anti-radical, anti-inflammatory and hepatoprotective effects. The anti-inflammatory and hepatoprotective activities may be attributed to anti-oxidant potential of the compound.

Chemical profiling and assessment of biological activities of wild Artemisia absinthium L. essential oil from Algeria

Artemisia absinthium L. (A. absinthium L.) is an important perennial shrubby plant widely employed in traditional medicine for the treatment of several ailments including gastritis, wound healing, and digestive disorders. In this study we assessed the chemical composition, as well as the antioxidant, anti-inflammatory and analgesic activities of a pure essential oil obtained from the aerial part of A. absinthium L., growing wild in Cherchell (Tipaza, Algeria). The essential oil, obtained through hydrodistillation using a Clevenger-type apparatus, underwent gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) analysis. The essential oil yield was 0.67 ± 0.02% (w/w), comprising 38 identified components, constituting 89.05% of the essential oil. Notable components included trans-thujone (54.7%), chamazulene (10.05%), β-eudesmol (4.7%), cis-thujone (4.2%), terpinen-4-ol (4.2%), and germacrene D (4.1%). Antioxidant activities were assessed via the DPPH٠free radical test (IC50: 489.19 ± 5.28 μg/mL) and the reducing power test (EC0.5: 424.95 ± 1.25 μg/mL). While the essential oil exhibited relatively low antioxidant activity compared to standard antioxidants, it showed significant antioxidant activity in the β-carotene-linoleic acid test (78.38 ± 0.83%). An acute toxicity study using various essential oil doses (10-100 mg/kg) revealed no signs of toxicity or mortality. Anti-inflammatory and antinociceptive activities were observed when testing the essential oil on carrageenan-induced paw edema in mice and acetic acid-induced pain in mice, with significant reductions (P < 0.05). In conclusion, A. absinthium L. essential oil possesses antioxidant, anti-inflammatory, and antinociceptive properties, suggesting its potential as a natural preservative ingredient in the food, cosmetics, and pharmaceutical industries.

A Comparative Study on Polyphenol, Flavonoid Content, Antioxidant and AntiInflammatory Capacity of Different Solvent Extract from Portulaca oleracea in Carrageenan-Induced Paw Edema in Mice

A Comparative Study on Polyphenol, Flavonoid Content, Antioxidant and AntiInflammatory Capacity of Different Solvent Extract from Portulaca oleracea in Carrageenan-Induced Paw Edema in Mice

Screening of Anti-inflammatory and Analgesic Activities of Caulerpa Racemosa from the Bay of Bengal, Bangladesh

Caulerpa spp; is a remarkably potential seaweed due to its pharmacological importance, high nutritional compositions, biological activities , and human health benefit. It is a species of ulvophyte green algae inhabiting mostly in the intertidal and shallow sub-tidal coastal regions in the Asia- Pacific and commonly consumed in South-East Asia for its high contents of vitamins and minerals. Besides its culinary uses, it is well-reported for its antibacterial, antifungal, diabetes, blood pressure, and lipid-lowering properties. However, to date, no extensive assessment of the diversity, distribution, and biological activity assay of these seaweeds found on the Bangladesh coast has been carried out. This study aimed at anti-inflammatory and analgesic studies of 50% ethanolic extract of Caulerpa racemosa. collected from St. Martin's Island, Bangladesh. Consequently, secondary metabolites such as steroids, flavonoids, glycoside, and saponin were also detected in the phytochemical assay. In the present study, 25 &amp; 50mg/kg body weight of ethanolic extract of C. racemosa was used in hot plate, acetic acid, formic acid, and carrageenan-induced paw edema in Swiss albino mice showing C. racemosa extract has significant analgesic and anti-inflammatory properties.&#x0D; Bioresearch Commu. 9(2): 1330-1339, 2023 (July)

Anti-inflammatory activity of Eucheuma denticulatum from Warambadi coast: In-vivo study model of carrageenan-induced paw oedema

Background: Chronic inflammatory diseases have been declared the leading cause of mortality in the world, with more than 50% of deaths associated with inflammatory cases. Based on previous studies, red algae contained antioxidants such as phenolics and flavonoids, which are correlated to their anti-inflammatory activity, including Eucheuma denticulatum. Objective: This study aims to analyse antioxidants and anti-inflammatory activity as well as the phenolic and flavonoid content of red algae E. denticulatum ethyl acetate extract (EDEE). Method: EDEE was macerated in ethyl acetate and the antioxidant activity was performed using the (2,2-diphenyl-1-picryl-hydrazyl-hydrate) DPPH method. Total phenolic and flavonoid content was quantified using the Folin-Ciocalteu and AlCl3 methods. The anti-inflammatory activity was analysed by measuring the percentage of anti-inflammatory activity in carrageenan-induced mice paw edema. Result: The results showed that the Inhibition concentration 50 (IC50) of EDEE was 1031.5 ppm with a total phenolic and flavonoid content of 81.34 ± 0.996mg gallic acid equivalents (GAE/g) and 5.64 ± 0.12 mg quercetin equivalents (QE/g) extract, respectively. In vivo study showed that EDEE of 20, 50, and 100mg/kg body weight (BW) provided the percentage of anti-inflammatory activity of 53.49%, 86.63%, and 78.49% respectively, which is significantly different (p&lt;0.05) compared to the negative control. Conclusion: EDEE 50mg/kg BW had the highest anti-inflammatory activity due to the presence of phenolic compounds.

Anti-Inflammatory Activities of Arnica montana Planta Tota versus Flower Extracts: Analytical, In Vitro and In Vivo Mouse Paw Oedema Model Studies

Arnica montana is well known for its anti-inflammatory properties. While the anti-inflammatory activity of Arnica flowers (Arnicae flos) has been extensively studied, that of the whole plant (Arnicae planta tota) is less characterized. We compared the ability of Arnicae planta tota and Arnicae flos extracts to inhibit the pro-inflammatory NF-κB-eicosanoid pathway, using several in vitro and in vivo assays. We showed that Arnicae planta tota inhibited NF-κB reporter activation, with an IC50 of 15.4 μg/mL (vs. 52.5 μg/mL for Arnicae flos). Arnicae planta tota also inhibited LPS-induced expression of ALOX5 and PTGS2 genes in human differentiated macrophages. ALOX5 and PTGS2 encode the 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2) enzymes that initialize the conversion of arachidonic acid into leukotrienes and prostaglandins, respectively. Arnicae planta tota inhibited 5-LO and COX-2 enzymatic activity in vitro and in human primary peripheral blood cells, with lower IC50 compared to Arnicae flos. Finally, Arnicae planta tota applied topically reduced carrageenan-induced mouse paw oedema more efficiently than Arnicae flos. Altogether, Arnicae planta tota displayed a superior anti-inflammatory activity compared to Arnicae flos, suggesting that Arnicae-planta-tota-containing products might be more effective in alleviating the manifestations of acute inflammation than those based on Arnicae flos alone.

Anxiolytic, analgesic and anti-inflammatory effects of Citrus maxima (Burm.) Merr. Seed extract in Swiss albino mice model

BackgroundCitrus maxima (Burm.) Merr. is traditionally used for its diverse pharmacological properties. Therefore, there remains a possibility that the seed extract may contain some bioactive compounds. The present study was carried out to evaluate the anxiolytic, analgesic, and anti-inflammatory effects of methanolic seed extract of Citrus maxima (MECM).MethodThe effect of MECM on the rodent central nervous system was evaluated using the hole-board and elevated plus-maze method. Analgesic effect was measured with the acetic acid-induced writhing and formalin-induced paw licking method. The anti-inflammatory effect was examined using a formalin and carrageenan-induced mice paw edema model.ResultsThe MECM at doses of 200 mg/kg and 400 mg/kg significantly (p < 0.01) increased the number of head dipping in the hole-board test. Additionally, the test subjects entered into the open arm and spent more time in it at an increased rate (p < 0.01) in the elevated plus-maze test. In the acetic acid-induced writhing method, the extract showed high potential (p < 0.001) as an analgesic agent. In the case of formalin-induced pain assessment, MECM demonstrated a significant effect (p < 0.01) at the early phase as a centrally acting anti-nociceptive agent and very high potential (p < 0.001) to reduce pain during the late phase as a peripherally acting analgesic. The extract also showed potency (p < 0.01) as an anti-inflammatory agent in formalin and carrageenan-induced mice paw edema test.ConclusionThe findings of the current study indicate that MECM can be a promising new candidate for searching novel anxiolytic, analgesic, and anti-inflammatory compounds through further investigation.

Leaf-buds of Pistacia atlantica: a novel source of bioactive molecules with high anti-inflammatory, antioxidant, anti-tyrosinase and antimicrobial properties.

In this study, for the first time, the anti-inflammatory, antioxidant, anti-tyrosinase and antimicrobial property of P. atlantica Desf. subsp. atlantica leaf-bud extracthave been investigated. The anti-inflammatory activity was determined in vivo by reducing carrageenan-induced hind paw edema in mice, while the antiradical function was evaluated using DPPH, total antioxidant capacity (TAC) and reduction power assays. The extract induced a significant reduction of the edema, from 1 to 6h in a dose-dependent manner (150, 200 and 300mg/kg). Histological observations of the inflamed tissues also confirmed this. An effective antioxidant activity of the plant samples was demonstrated, showing an EC50 = 0.183 ± 0.005mg/mL for the DPPH test, a value of 28.776 ± 2.541mg AAE/g for the TAC and an EC50 = 0.136 ± 0.003mg/mL for reducing power. The leaf-bud extract also revealed a good antimicrobial activity against S. aureus and L. monocytogenes (mean diameter of inhibition zones of 13.2 and 17.0mm, respectively), while a slight antifungal effect was observed. The plant preparation was then documented to inhibit tyrosinase activity, with an EC50 value of 0.098 ± 0.00mg/mL in a dose-dependent manner. HPLC-DAD analysis revealed that dimethyl-allyl caffeic acid and rutin were the most abundant molecules. The current data documented that P. atlantica leaf-bud extract has strong biological properties and constitutes a potential source of pharmacological molecules.

Anti-inflammatory, Antinociceptive, and Toxicological Properties of Uvaria comperei Stem Crude Extract and Fractions.

The present study was carried out to investigate the anti-inflammatory activity of a methanolic extract and fractions of Uvaria comperei stems. The crude extract was obtained by maceration of the powder in methanol and fractions by vacuum chromatography from the methanolic extract. To study the anti-inflammatory activity in vitro, red blood cell lysis inhibition assay and albumin denaturation inhibition were performed, while in vivo measurements of carrageenan-induced paw oedema and formalin-induced pain in albino mice were performed. Acute toxicity and cytotoxicity studies of the fraction F2 were performed, as well as its HPLC, and some biochemical parameters were quantified. Uvaria comperei crude extract (UCCE) at 250 and 500 μg/mL completely inhibited albumin denaturation, while decreasing 75.5% of heat blood cell lysis at 500 μg/mL. The fractions 128-136 (F3), 10-11 (F1), and 56-62 (F2) at 500 μg/mL displayed a significant anti-inflammatory activity with percentages of inhibition of 60.5, 67.4, and 100%, respectively. Administration of fraction F2 (25, 50, and 100 mg/kg, p.o.) produced a dose-dependent inhibition of formalin-induced pain of 60.2% at 50 mg/kg in the neurogenic phase (p < 0.05) and 70.2% at 25 mg/kg in the inflammatory phase (p < 0.05). Similarly, the time-dependent increase in carrageenan-induced paw circumference induced by carrageenan was inhibited by pretreatment with F2: 50% of inhibition at 25 mg/kg after 30 min (p < 0.05) and 96.5% inhibition at 25 mg/kg after 6 h (p < 0.05). In this research, the fraction F2 presented its maximum analgesic property at 50 mg/kg, while it presented the highest anti-inflammatory property at 25 mg/kg. The oral lethal median dose (LD50) of F2 was determined to be greater than 2000 mg/kg; further low cytotoxicity in RAW cells was also observed. Overall, this work shows that the methanolic crude extract and fractions, mainly F2, of Uvaria comperei stem have interesting anti-inflammatory properties.

The dichloromethane extract of Callicarpa longissima rich in diterpenoid phenols exerts anti-inflammatory effect via inhibiting the TLR4/NF-κB signaling pathway

Ethnopharmacological relevanceCallicarpa longissima is a typical Yao ethnomedicine that has been used to treat arthritis in China. Our previous study found that the dichloromethane extract (DCME) of C. longissima showed anti-inflammatory activity in vitro. However, the anti-inflammatory mechanism and detailed chemical composition of DCME remain unclear, which lead to the original interest of this study. Aim of the studyThe study aimed to evaluate the anti-inflammatory properties of the DCME from C. longissima and further explore the accurate chemical components responsible for this active extract. Materials and methodsThe anti-inflammatory activity of DCME in vivo was tested with carrageenan-induced mice paw edema model. Its anti-inflammatory mechanism was explored with LPS-stimulated RAW264.7 macrophages model. The compounds in DCME were isolated by repeated column chromatography and their structures were identified on the basis of nuclear magnetic resonance spectroscopy. The anti-inflammatory activities of the isolates in vitro were also tested by suppressing releases of inflammatory mediators (NO, IL-6 and TNF-α) in RAW264.7 macrophages model. In addition, the molecular docking analysis, which evaluated the potential interaction between the compounds and Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB), was performed. ResultsDCME effectively alleviated the mice paw edema induced by carrageenan. In LPS-stimulated RAW264.7 cells, DCME significantly decreased the production of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) via inhibiting their mRNA transcription, down-regulated the expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of alpha inhibitor of NF-κB (IκBα), NF-κB p65, and degradation of IκBα. Twelve diterpenoid phenols were identified from DCME, and they not only showed different inhibitory effects on the production of NO, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells, but also could bind to TLR4 and NF-κB as analyzed by molecular docking. ConclusionsTaken together, DCME from C. longissima could inhibit inflammatory response both in vitro and in vivo, which is mainly attributed to the synergistic effect of abundant diterpenoid phenols through inhibiting the TLR4/NF-κB signaling pathway, and might be a promising agent for the treatment of inflammatory diseases.

Synthesis and characterization of biologically active flurbiprofen amide derivatives as selective prostaglandin-endoperoxide synthase II inhibitors: In vivo anti-inflammatory activity and molecular docking

A novel series of twenty two flurbiprofen amides (1−22) were designed and synthesized in good to excellent yields by reacting flurbiprofen acid with various aromatic/aliphatic primary amines in the presence of 1,1‑carbonyldiimidazole (CDI) in basic medium using acetonitrile as solvent. Structures of the synthesized derivatives were elucidated with the help of HR-ESI-MS, 1H-, and 13C NMR spectroscopy and finally screened them for their in-vivo anti-inflammatory potential using carrageenan induced mice paw oedema assay. Among the series, four compounds (8, 14, 15, and 20) displayed excellent activity ranging from 59.0 to 77.7 % decrease, while eight compounds (1, 3, 7, 10, 12, 13, 17, and 18) exhibited good activity in the decrease range of 37.0–50.0 %. Additionally, four compounds (2, 6, 16, and 22) attributed less activity, while the remaining six compounds (4, 5, 9, 11, 19, and 21) were found to be inactive. Furthermore, the In-silico studies were executed on the synthesized derivatives in order to explain the binding interface of compounds with the active sites of prostaglandin endoperoxide-synthase II enzyme.

Smart redox-sensitive micelles based on chitosan for dasatinib delivery in suppressing inflammatory diseases

Dasatinib (DAS) exhibits anti-inflammatory effects by retrieving the balance between inflammatory and anti-inflammatory cytokines secreted by macrophages. The aim of this study was the development of redox-responsive micelles with the potential of passive targeting and on-demand drug release for DAS delivery to macrophages. For this purpose, two molecular weights of chitosan (CHIT) were conjugated to DAS at different molar ratios using 3,3′-dithiodipropionic anhydride (DTDPA) as disulfide bond containing linker to synthesize a series of CHIT-S-S-DAS amphiphilic conjugates. Micelles obtained by the sonication method had particle sizes of 129.3–172.2 nm, zeta potentials of +17.5 to +20.9 mV, drug contents of 0.90–7.20 %, CMC values of 35.3–96.6 μg/ml, and exhibited redox-responsive in vitro drug release. Optimized micelles were non-toxic and dramatically more efficient than non-redox responsive micelles in reducing TNF-α and IL-6 and increasing IL-10 secretion from LPS-stimulated RAW264.7 cells. Furthermore, the redox-responsive micelles were able to reduce the mice paw edema, reduce the plasma levels of pro-inflammatory cytokines and increase plasma level of IL-10, considerably more than free DAS and non-redox responsive micelles in carrageenan-induced mice paw edema model of inflammation.