Xylene-induced Ear Edema Model Research Articles

A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies

A variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated their anti-inflammatory activity in vitro and in vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE2 inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 enzyme at 5 μM via ELISA experiment. Compound L-37 (1 μM) also inhibited the PGF1 production as well as the expression of COX-1, but displayed weak inhibition activity to the Leukotrienes (LT) and Thromboxane B2 (TXB-2) production. However, the expression of 5-LOX was significantly inhibited by compound L-39 at 5 μM. Xylene-induced ear edema model was explored for in-vivo anti-inflammatory evaluation, compound L-37 showed similar inhibitory activity compared with celecoxib, approximately 80% at 50 mg/kg dosage. Every outcome showed that the newly synthesized compounds can effectively inhibit inflammation.

Anti-inflammatory effects and related mechanisms in vitro and in vivo of Hedychium coccineum rhizome essential oil

Ethnopharmacological relevanceHedychium coccineum rhizome is an anti-inflammatory ethnomedicine used to remedy inflammation-related swelling and bronchial asthma. Aim of the studyThe study aimed to analyze the phytochemical constituents of H. coccineum rhizome essential oil (EO) and evaluate its in vitro and in vivo anti-inflammatory effects and underlying mechanisms. Materials and methodsPhytochemical constituents of H. coccineum rhizome EO were analyzed using GC-FID/MS. In RAW264.7 macrophages induced by LPS, blockade of PGE2, NO, IL-1β, IL-6, and TNF-α secretion by H. coccineum rhizome EO was measured, and then Western blot, qRT-PCR, and immunofluorescent staining were used to evaluate its underlying mechanisms. Moreover, we used the xylene-induced ear edema model for testing anti-inflammatory potential in vivo and examined auricular swelling as well as tissue and serum contents of IL-1β, IL-6, and TNF-α. ResultsEO's main components were E-nerolidol (40.5%), borneol acetate (24.8%), spathulenol (4.5%), linalool (3.8%), elemol (3.5%), and borneol (3.4%). In RAW264.7 cells stimulated by LPS, EO downregulated the expression of pro-inflammatory enzyme (iNOS and COX-2) genes and proteins, thereby suppressing pro-inflammatory mediators (NO and PGE2) secretion. Simultaneously, it reduced TNF-α, IL-1β, and IL-6 release by downregulating their mRNA expression. Besides, H. coccineum EO attenuated LPS-stimulated activation of NF-κB (by reducing IκBα phosphorylation and degradation to inhibit NF-κB nuclear translocation) and MAPK (by downregulating JNK, p38, and ERK phosphorylation). In xylene-induced mouse ear edema, EO relieved auricular swelling and lowered serum and tissue levels of TNF-α, IL-1β, and IL-6. ConclusionsH. coccineum EO had powerful in vivo and in vitro anti-inflammatory effects by inhibiting MAPK and NF-κB activation. Hence, H. coccineum EO should have great potential for application in the pharmaceutical field as a novel anti-inflammatory agent.

The antioxidant, anti-inflammatory and analgesic activity effect of ethyl acetate extract from the flowers of Syringa pubescens Turcz

Ethnopharmacological relevanceSyringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis.Aim of the study: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. MethodsHPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and β-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1β) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. ResultsHPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1β were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. ConclusionThe study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.

Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (− 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

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.

Molecular docking, DFT studies, and anti-inflammatory evaluation of peshawaraquinone isolated from Fernandoa adenophylla

In recent years, there has been growing interest in exploring natural compounds with anti-inflammatory properties for potential therapeutic applications. This study focuses on investigating the anti-inflammatory potential of peshawaraquinone (PAQ), a compound isolated from Fernandoa adenophylla, which is known for its local use in pain relief. We aim to evaluate the efficacy of peshawaraquinone in both in vitro and in vivo models and gain insights into its mode of action. In the in vitro Human red blood cell (HRBC) assay, various concentrations of peshawaraquinone were tested for their ability to inhibit the hemolysis of red blood cells, a well-established indicator of anti-inflammatory activity. The results demonstrated a maximum percent inhibition of 79.69 at a concentration of 100 µM, indicating significant anti-inflammatory potential. Furthermore, the in vivo xylene-induced ear edema model was employed to assess the compound’s efficacy in reducing inflammation. Xylene was topically applied to the ear to induce edema, and peshawaraquinone was administered to evaluate its inhibitory effects. The findings revealed a substantial 74.19% reduction in ear edema, accompanied by decreased ear thickness and histopathological improvements, such as inhibited cell infiltration and epidermal hyperplasia. To gain further insights into the compound’s mechanism of action, density functional theory (DFT) calculations were performed to investigate its spectroscopic characteristics and geometric properties. Additionally, docking studies were conducted on key targets involved in inflammation, including COX-1 and COX-2. In conclusion, this study showcases the significant anti-inflammatory potential of peshawaraquinone, offering promising prospects for its use as a natural anti-inflammatory agent. The results from both in vitro and in vivo models, as well as the mechanistic insights gained from computational analyses, provide a solid basis for further exploration of peshawaraquinone’s therapeutic applications. Communicated by Ramaswamy H. Sarma

Usefulness of Lipidic Nanoparticles of Curcumin and Tetrahydrocurcumin for Skin Inflammation: A Comparative Study

Background: Yellow curcumin, the “Indian Gold” is known since ancient times to modulate the activities of a wide variety of targets. The voluminous literature and several patents are a proof of the therapeutic value of curcumin. Tetrahydrocurcumin (THC), however, has remained as an unexplored molecule although its cosmeceutical properties have been documented. Their compromised bioavailability, poor aqueous solubility (curcumin 11 ng/mL, THC 56ng/mL), high log P (Cur: 3.28; THC: 2.98) are hurdles for developing as potential drugs. Objective: This article discusses the usefulness of lipidic nanoparticles of curcumin and THC for skin inflammation. Method: Nanocouturing to produce lipidic nanoparticles (LNs) of curcumin and THC was done via an optimized microemulsification technique. LNs were characterized by FTIR, TEM, pharmacokinetics, and pharmacodynamic study. Results: FTIR reflected the suitable incorporation of drugs into LNs. TEM examination revealed a spherical to ellipsoidal shape with a particle size of &lt;200 nm. In vitro release study indicates the release of both drugs is between 70-80% within 24 h. Ex-vivo permeation studies confirmed the ability of LNs to cross the stratum corneum. Stability studies (Q1AR2) indicated that both were stable, safe, and nonirritating (OECD 404). Xylene induced ear edema model of inflammation showed both molecules to possess equivalent abilities to treat inflammation. Conclusion: Curcumin being yellow in color is unstable at physiological pH and plasma and possesses poor bioavailability, while THC is a colorless stable molecule, making it a molecule of choice to be developed as an effective topical product.

Anti-inflammation activity of Zhizi Jinhua Pills and overall quality consistency evaluation based on integrated HPLC, DSC and electrochemistry fingerprints.

Zhizi Jinhua Pills (ZZJHP), a compound preparation composed of 8 traditional Chinese medicines (TCM), is widely used clinically to clearing heat, purging fire, cooling blood and detoxifying. However, the studies on its pharmacological activity and the determination of active compounds are relatively few. There is a lack of quality control methods that can reflect the effectiveness of the drug. The objective was to construct fingerprint profiles, conduct a spectrum-effect relationship study and establish an overall quality control method for ZZJHP through anti-inflammatory and redox activity studies. Firstly, anti-inflammatory activity was tested using the xylene-induced ear edema model in mice. Then, Five-wavelength fusion HPLC fingerprint, electrochemical fingerprint, and Differential scanning calorimetry (DSC) profiling were established to evaluate ZZJHP more comprehensively, where Euclidean quantified fingerprint method (EQFM) was proposed for the similarity assessment of these three fingerprints. Moreover, the spectrum-activity relationship of HPLC-FP and DSC-FP with electrochemical activity helped explore the active components or ranges in the fingerprint. Finally, integrated analysis of HPLC, DSC and electrochemistry were used for the quality screen of samples from different manufacturers. ZZJHP was found to significantly decrease the levels of both TNF-α and IL-6 in the mice. Qualitatively, the integrated similarity Sm of 21 samples were all greater than 0.9, indicating the great consistency in chemical composition. Quantitatively, 9 batches of samples were classified as Grade1∼4; 6 batches of samples were classified as Grade5∼7 due to higher PINT; 6 batches of samples were classified as Grade4∼5 due to lower PINT. EQFM can qualitatively and quantitatively characterize the fingerprint profile information from an overall perspective. This strategy will contribute to the quantitative characterization of TCM and promote the application of fingerprint technology in the phytopharmacy field.

Fatty-Acid-Rich Agave angustifolia Fraction Shows Antiarthritic and Immunomodulatory Effect.

Agave angustifolia is a xerophytic species widely used in Mexico as an ingredient in sweet food and fermented beverages; it is also used in traditional medicine to treat wound pain and rheumatic damage, and as a remedy for psoriasis. Among the various A. angustifolia extracts and extract fractions that have been evaluated for their anti-inflammatory effects, the acetonic extract (AaAc) and its acetonic (F-Ac) and methanolic (F-MeOH) fractions were the most active in a xylene-induced ear edema model in mice, when orally administered. Four fractions resulting from chemically resolving F-Ac (F1-F4) were locally applied to mice with phorbol 12-myristate 13-acetate (TPA)-induced ear inflammation; F1 inhibited inflammation by 70% and was further evaluated in a carrageenan-induced mono-arthritis model. When administered at doses of 12.5, 25, and 50 mg/kg, F1 reduced articular edema and the spleen index. In addition, it modulated spleen and joint cytokine levels and decreased pain. According to a GC-MS analysis, the main components of F1 are fatty-acid derivatives: palmitic acid methyl ester, palmitic acid ethyl ester, octadecenoic acid methyl ester, linoleic acid ethyl ester, and oleic acid ethyl ester.

Hedychium flavum flower essential oil: Chemical composition, anti-inflammatory activities and related mechanisms in vitro and in vivo

Ethnopharmacological relevanceHedychium flavum, an ornamental, edible, and medicinal plant, is extensively cultivated as a source of aromatic essential oils (EO). Its flower is a traditional Chinese medicine for treating inflammation-related diseases like indigestion, diarrhea, and stomach pain. In particular, H. flavum flower EO has been used in cosmetics and as an aromatic stomachic to treat chronic gastritis in China. Aim of the studyThis research aimed to analyze H. flavum flower EO's chemical composition and explore its anti-inflammatory activities and related mechanisms in vitro and in vivo. Materials and methodsEO's chemical composition was determined by GC-FID/MS analysis. For in vitro test, the anti-inflammatory activity of EO was demonstrated by measuring the LPS-induced release of NO, PGE2, IL-1β, TNF-α, and IL-6 in RAW264.7 macrophages, and then its related mechanisms were explored using qRT-PCR, western blot, and immunofluorescent staining analysis. Next, EO's in vivo anti-inflammatory potential was further evaluated using a xylene-induced ear edema model, in which ear swelling and TNF-α, IL-6, and IL-1β levels in serum and tissue were examined. ResultsThe main components of EO were β-pinene (20.2%), α-pinene (9.3%), α-phellandrene (8.3%), 1,8-cineole (7.1%), E-nerolidol (5.4%), limonene (4.4%), borneol (4.1%), and β-caryophyllene (3.7%). For the anti-inflammatory activities in vitro, EO dramatically reduced the LPS-stimulated NO and PGE2 release by suppressing the mRNA and protein expression of iNOS and COX-2. Meanwhile, it remarkably decreased IL-6, TNF-α, and IL-1β production by inhibiting their mRNA levels. Related mechanism studies indicated that it not only inhibited IκBα phosphorylation and degradation, leading to blockade of NF-κB nuclear transfer but also suppressed MAPKs (ERK, p38, and JNK) phosphorylation in LPS-stimulated RAW264.7 cells. Further in vivo assay showed that EO ameliorated xylene-induced ear edema in mice and reduced TNF-α, IL-6, and IL-1β levels in serum and tissue. ConclusionsH. flavum EO exerted significant anti-inflammatory activity in vivo and in vitro, and its mechanism of action is related to the inhibition of MAPK and NF-κB activation. Thus, H. flavum EO could be considered a novel and promising anti-inflammatory agent and possess high potential for utilization in the pharmaceutical field.

Efficacy of 2-Hydroxyflavanone in Rodent Models of Pain and Inflammation: Involvement of Opioidergic and GABAergic Anti-Nociceptive Mechanisms

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg−1, showed considerable analgesic, anti-inflammatory effects, as well as efficacy against neuropathic pain. Naloxone and pentylenetetrazol at 1 and 15 mg kg−1 antagonized the anti-nociceptive activities of 2-hydroxyflavanone indicating the involvement of opioidergic and GABAergic mechanisms. In the static allodynia model, combination of gabapentin 75 mg kg−1 with 2-HF at 15, 30, 45 mg kg−1 doses exhibited considerable efficacy. In cold allodynia, 2-hydroxyflavanone, at doses of 15, 30 and 45 mg kg−1 and in combination with gabapentin (75 mg kg−1), demonstrated prominent anti-allodynic effects. The paw withdrawal latency was considerably increased in gabapentin + cisplatin treated groups. Moreover, cisplatin + 2-hydroxyflavanone 15, 30, 45 mg kg−1 showed increases in paw withdrawal latency. Likewise, considerable efficacy was observed for 2-hydroxyflavanone in thermal hyperalgesia and dynamic allodynia models. Our findings suggest that 2-hydroxyflavanone is a potential remedy for pain syndrome, possibly mediated through opioidergic and GABAergic mechanisms.

Evaluation of Phytochemistry and Pharmacological Properties of Alnus nitida.

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds’ complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70–80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40–60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography–mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.

Investigation of Wound Healing and Anti-Inflammatory Activities of Leaf Gel of Aloe trigonantha L.C. Leach in Rats.

BackgroundTraditionally Aloe trigonantha leaf is used for the treatment of different diseases. However, there were no in vivo studies which prove its claimed use for wound healing and anti-inflammatory activity. Therefore, the present study aimed at evaluating the in vivo wound healing and anti-inflammatory effects of the leaf gel of the plant in rats.MethodsThe leaf gel powder of the Aloe trigonantha was prepared after the gel gets lyophilized. It was evaluated for wound healing activity topically by incorporating it in a simple ointment base at a concentration of 5% (w/w) and 10% (w/w). Excision and incision models were used for wound healing activity in rats. For the excision wound model, wound contraction and period of epithelialization were evaluated, while wound tensile strength was evaluated using an incision wound model. A Xylene-induced ear edema model and cotton pellet-induced granuloma model were used for anti-inflammatory study. The leaf gel powder of Aloe trigonantha was given orally at a dose of 100, 200, and 400 mg/kg in both models of anti-inflammatory studies. An anti-inflammatory effect was measured by reduction of ear edema weight and reduction of wet exudate and dry granuloma weight in both of xylene-induced ear edema and cotton pellet-induced granuloma models, respectively.ResultsTreatment of wounds with ointment containing 5% and 10% (w/w) of the gel exhibited a significantly increased wound contraction rate, shorter epithelialization time, and higher skin breaking strength (p<0.05) compared to controls. Aloe trigonantha leaf gel powder also produced dose-dependent significant reductions (p<0.05) of inflammation compared to control in both models.ConclusionData obtained from this study collectively indicated that Aloe trigonantha is a potential wound-healing and anti-inflammatory agent in rat models of wound and inflammation which provides evidence for the traditional claim.

Synthesis and Activity Evaluation of Some Pyrazole–Pyrazoline Derivatives as Dual Anti-Inflammatory and Antimicrobial Agents

In this study, 18 pyrazole derivatives coupled with pyrazoline were synthesized and screened for their anti-inflammatory and antimicrobial activities. All the target compounds were synthesized smoothly and characterized using 1H NMR, 13C NMR, and HRMS. In vitro lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α model and in vivo xylene-induced ear-edema model were used to evaluate their anti-inflammatory activity. Antimicrobial activity against several Gram-positive strains and Gram-negative strains was evaluated using a serial dilution method. Pharmacological results indicated that most of the compounds markedly inhibited the expression of TNF-α at the concentration of 20 μg/mL. Compounds 9b showed 66.4% inhibition for the LPS-induced TNF-α release, which was superior than that of the positive control drug dexamethasone (DXMS). And compounds 4a, 4b, 5a, 5b, 6b, and 9b showed comparable inhibition activity to DXMS. In xylene-induced ear-edema model, compound 4a inhibited edema by 48.71%, which was more effective than DXMS (47.18%) in inhibiting xylene-induced ear edema. Compound 4b, 5a, 5b, 6b, and 9b showed inhibition of 36.82%, 27.65%, 45.87%, 31.78%, and 43.67%, respectively. Furthermore, compounds 4a, 5a, 5b, and 9b displayed broad-spectrum antimicrobial activity against several Gram-positive and Gram-negative bacterial. These compounds, 4a, 5a, 5b, and 9b, possess both anti-inflammatory and antimicrobial activities, thus are worth further investigation to enhance their antimicrobial activities for the development of new class of dual anti-inflammatory–antimicrobial agents.

New Hydrazone Derivatives of Pyrazole-4-carboxaldehydes Exhibited Anti-inflammatory Properties

Background: Several series of hydrazone derivatives of pyrazole-4-carboxaldehydes (4- 11) were designed and synthesized to screen their inflammatory activity. Methods: The products were characterized by 1H NMR, 13C NMR and HRMS. In vitro LPS-induced TNF-α model and in vivo xylene-induced ear-edema model were used to evaluate their antiinflammatory activity. Results and Conclusion: Bioassays indicated that most of the compounds markedly inhibited the expression of TNF-α at the concentration of 10 µg/mL. Compounds 7b and 11c, two of the most potent compounds, exhibited TNF-α inhibitory ability in a dose-dependent manner with IC50 values of 5.56 and 3.69 µM, respectively. In vivo, intraperitoneal administration with 7b and 11c markedly inhibited the ear edema at the doses of 20 and 50 mg/kg. Compound 11c, inhibited edema by 49.59 % at the dose of 20 mg/kg, was comparable to the reference drug dexamethasone at the same dose (with an inhibition of 50.49 %). To understand the binding pattern, molecular docking of representative 7b and 11c was performed, which demonstrated that both compounds have a forceful binding with the TNF-α, and that the phenyl and hydrazide moieties of them play a significant role in binding with the target site.

Protective effects of Ginger Essential Oil (GEO) against chemically-induced cutaneous inflammation

Abstract The inhibitory effects of ginger essential oil (GEO) on chemically-induced cutaneous inflammation were investigated. Three kind of experimental murine models, such as xylene-induced ear edema model, carrageenan-induced paw edema model and 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) model were exploited to evaluate the anti-inflammatory effect of GEO. Results showed that GEO lowered the ear swelling rate induced by xylene and decreased paw edema rate induced by carrageenan of mice with cutaneous inflammation significantly. Treatment with GEO significantly inhibited DNFB-induced ear swelling degree and rate, and alleviated the inflammatory symptoms of ear skin lesions of ACD model mice markedly. Treatment with GEO decreased the gene expression of the inflammatory cytokines of auricular tissues such as TLR-2, TLR-4, TNF-α, IFN-γ, IL-1β, IL-8, and increased the gene expression of cytokine IL-4 significantly. In conclusion, GEO has anti-inflammatory and protective effect on chemically-induced cutaneous inflammation.

Synthesis and Biological Evaluation of Some Pyrazole Derivatives, Containing (Thio) Semicarbazide, as Dual Anti-Inflammatory Antimicrobial Agents

Background:Several series of pyrazole derivatives containing (thio) semicarbazide (4a-4h, 5a-5l, 6a-6f, 7a-7c) were designed and synthesized to screen dual inflammatory and antimicrobial activities.Methods:The products were characterized by1H NMR, 13C NMR and HRMS. In vitro LPS-induced TNF-α model and in vivo xylene-induced ear-edema model were used to evaluate their antiinflammatory activity. Their in vitro antimicrobial activities were evaluated using a serial dilution method against several gram-positive strains, gram-negative strains and a fungi strain.Results:Bioassays indicated that most of the compounds markedly inhibited the expression of TNF- α at the concentration of 20 µg/mL Compounds 5i, 6b, and 7b had comparable in vivo antiinflammatory activity to the reference drug dexamethasone at the dose of 50 mg/kg. In addition, several compounds showed antimicrobial activity against different strains, and compounds 5g and 5h exhibited potent inhibitory activities with the MIC value of 8 µg/mL against the Streptococcus pneumoniae CMCC 31968 and Staphylococcus aureus CMCC 25923, respectively. Compound 7b, which exhibited both anti-inflammatory and antimicrobial activities, should be studied as it is or after derivatization.Conclusion:It can be concluded that pyrazoles, with (thio)-semicarbazone moieties, have the potential to be developed into new anti-inflammatory agents.

Steroidal glycosides from the underground parts of Hosta ventricosa and their anti-inflammatory activities in mice

Two new pregnane glycosides, 2α, 3β-dihydroxy-5α-pregn-16-en-20-one-3-O-{α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-galactopyranoside} (1) and 2α, 3β-dihydroxy-5α-pregn-16-en-20-one-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside}(2), have been isolated along with two known spirostanol saponins from the underground parts of Hosta ventricosa. Their structures were elucidated on the basis of chemical and spectral evidence. The anti-inflammatory activities of these steroidal glycosides were evaluated using a xylene-induced ear edema model. Our results indicated that the compounds exhibited promising anti-inflammatory activities.

Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin.

Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.

Urginea indica attenuated rheumatoid arthritis and inflammatory paw edema in diverse animal models of acute and chronic inflammation

Ethnopharmacological relevanceUrginea indica has been used in the traditional system of medicine to treat various inflammatory diseases. Aim of the studyPresent study investigates the effects of aqueous and ethanolic extracts of U. indica on joint inflammation using different models of acute and chronic inflammation. Materials and methodsFCA-induced arthritic rat model, a model of chronic joint inflammation, was used to evaluate the anti-arthritic effects of plant extracts (500 mg/kg, each extract). Macroscopic arthritic scoring, digital water plethysmometery, and histopathological evaluation (H & E staining) were performed to measure the severity of arthritis. Acute inflammatory models like, carrageenan-, histamine- and serotonin-induced paw edema models were used to evaluate effects of U. indica, and supported by xylene-induced ear edema model. ResultsBoth extracts significantly inhibited arthritic development, paw edema, bone erosion, pannus formation, and infiltration of inflammatory cells. Treatment with U. indica extracts resulted in almost normalization of altered counts of white blood cells (WBCs), platelets, and red blood cells (RBCs), along with Hb content. Both extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by non-significant difference of alanine aminotransferase (ALT), aspartate transaminase (AST), urea, and creatinine levels among all groups. U. indica significantly attenuated carrageenan-induced paw edema. There are several mechanisms involved in the attenuation of carrageenan-induced paw edema; inhibition of autacoids is one of those important mechanisms. The autacoid inhibition was confirmed by reduction of histamine- and serotonin-induced paw edema found in plant extract treated groups. Suppression of xylene-induced ear edema by plant extract further validated the suggested mechanism of autacoid inhibition. GC-MS analysis showed the presence of isopropyl palmitate in the highest quantity (26.852%). ConclusionsThis study validated the folkloric uses of U. indica and showed that plant possessed anti-arthritic and anti-inflammatory properties which might be ascribed to inhibition of autacoids.