Central and peripheral mechanism of MOTS-c attenuates pain hypersensitivity in a mice model of inflammatory pain.

BACKGROUND: Inflammatory pain is caused by damaged tissue or noxious stimuli, accompanied by the release of inflammatory mediators that often leads to severe hyperalgesia and allodynia with limited therapy options. Recently, a novel mitochondrial-derived peptide (named MOTS-c) was reported to regulate obesity, metabolic homeostasis and inflammatory response. The aim of this study was to investigate the effects of MOTS-c and its related regulatory mechanisms involved in inflammatory pain. METHODS: Male Kunming mice (8-10 weeks-old) were intraplantar injected with formalin, capsaicin, λ-Carrageenan and complete Freund adjuvant (CFA) to establish acute and chronic inflammatory pain. The effects of MOTS-c on the above inflammatory pain mice and its underlying mechanisms were examined by behavioral tests, quantitative polymerase chain reaction (qPCR), western blotting, enzyme linked immunosorbent assay (ELISA), immunohistochemistry (IHC) and immunofluorescence (IF). RESULTS: Behavioral experiments investigated the potential beneficial effects of MOTS-c on multiple acute and chronic inflammatory pain in mice. The results showed that MOTS-c treatment produced potent anti-allodynic effects in formalin-induced acute inflammatory pain, capsaicin-induced nocifensive behaviors and λ-Carrageenan/CFA-induced chronic inflammatory pain model. Further mechanistic studies revealed that central MOTS-c treatment significantly ameliorated CFA-evoked the release of inflammatory factors and activation of glial cells and neurons in the spinal dorsal horn. Moreover, peripheral MOTS-c treatment reduced CFA-evoked inflammatory responses in the surface structure of hindpaw skin, accompanied by inhibiting excitation of peripheral calcitonin gene-related peptide (CGRP) and P2X3 nociceptive neurons. CONCLUSIONS: The present study indicates that MOTS-c may serve as a promising therapeutic target for inflammatory pain.

Design, QSAR Methodology, Synthesis and Assessment of Some Structurally Different Xanthone Derivatives as Selective Cox-2 Inhibitors for their Anti-inflammatory Properties.

INTRODUCTION: Inflammation can be defined as a complex biological response that is produced by body tissues to harmful agents like pathogens, irritants, and damaged cells and thereby acts as a protective response incorporating immune cells, blood vessels, and molecular mediators. Histamine, serotonin, bradykinin, leukotrienes (LTB4), prostaglandins (PGE2), prostacyclins, reactive oxygen species, proinflammatory cytokines like IL-1, IL-11, TNF- anti-inflammatory cytokines like IL-4, IL-10, IL-11, IL-6 and IL-13, etc. all have different effects on both pro and anti-inflammatory mediators. Incorporation of combinatorial chemistry and computational studies have helped the researchers to design xanthones moieties with high selectivity that can serve as a lead compound and help develop potential compounds that can act as effective COX-2 inhibitors. The study aims to design and develop different series of substituted hydroxyxanthone derivatives with anti-inflammatory potential. METHODS: The partially purified synthetic xanthone derivatives were orally administered to the carrageenan induced paw oedemic rat models at the dose of 100 mg/kg, and their effect in controlling the degree of inflammation was measured at the time interval of 30 min, 1, 2, 3, 4 and 6 hrs. respectively. Further, these compounds were also subjected to modern analytical studies like UV, IR, NMR and mass spectrometry or their characterization. RESULTS: The results drawn out of the in silico, in vitro, in vivo and analytical studies concluded that the hydroxyxanthone derivatives can obstruct the enzyme COX-2 and produce anti-inflammatory action potentially. CONCLUSION: With the aim to evaluate the compounds for their anti-inflammatory activity, it was observed that the newly designed xanthonic compounds also possess a safe toxicity margin and hence can be utilized by the researchers to develop hybrid xanthonic moieties that can specifically target the enzyme COX-2.

Preventing upper respiratory tract infections with prophylactic nasal carrageenan: a feasibility study.

Aim: To observe upper respiratory tract infection (URTI) symptoms, rhinovirus levels and compliance with daily carrageenan nasal spray. Methods: 102 adults were randomized to carrageenan or saline placebo three times daily for 8 weeks and URTI symptoms were recorded. A control group (n = 42) only recorded URTI symptoms. Participants collected nasal swabs when symptomatic. Results: Regular daily carrageenan prophylaxis resulted in consistent but nonsignificant reductions in URTI symptoms versus the placebo group. Saline placebo decreased and increased some cold symptoms compared with no treatment. Conclusion: Daily prophylactic administration of antiviral carrageenan may not significantly reduce URTI symptoms. Due to low compliance, use in a population with specific reasons to avoid URTIs may be more appropriate. Disease-specific outcomes may be more useful than symptom reporting.

HPLC and GC Characterization of Dicliptera bupleuroides Aerial Parts and Evaluation of Its Anti-Inflammatory Potential in Vitro, in silico and in Vivo Using Carrageenan and Formalin Induced Inflammation in Rat Models.

The current study aimed to evaluate the anti-inflammatory activity of Dicliptera bupleuroides Nees aerial parts methanol extract and its different fractions namely hexane, chloroform, ethyl acetate and butanol in vitro using cyclooxygenase inhibitory assay (COX-2). In vivo anti-inflammatory evaluation was performed using carrageenan and formalin induced inflammation in rat models followed by molecular docking. High performance liquid chromatography (HPLC) and gas chromatography coupled with mass chromatography (GC/MS) analyses were used for chemical analyses of the tested samples. The tested samples showed significant inhibition in COX-2 inhibitory assay where methanol extract (DBM) showed the highest inhibitory potential at 100 µg/mL estimated by 67.86 %. At a dose of 400 mg/kg, all of the examined samples showed pronounced results in carrageenan induced acute inflammation in rat model at 4th h interval with DBM showed the highest efficiency displaying 65.32 % inhibition as compared to the untreated rats. Formalin model was employed for seven days and DBM exhibited 65.33 % and 69.39 % inhibition at 200 and 400 mg/kg, respectively approaching that of the standard on the 7th day. HPLC revealed the presence of caffeic acid, gallic acid and sinapic acid, quercetin and myricetin in DBM. GC/MS analysis of its hexane fraction revealed the presence of 16 compounds belonging mainly to fatty acids and sterols that account for 85.26 % of the total detected compounds. Molecular docking showed that hexadecanoic acid followed by decanedioic acid and isopropyl myristate showed the best fitting within cyclooxygenase-II (COX-II) while nonacosane followed by hexatriacontane and isopropyl myristate revealed the most pronounced fitting within the 5-lipoxygenase (5-LOX) active sites. Absorption, metabolism, distribution and excretion and toxicity prediction (ADMET/ TOPKAT) concluded that most of the detected compounds showed reasonable pharmacokinetic, pharmacodynamic and toxicity properties that could be further modified to be more suitable for incorporation in pharmaceutical dosage forms combating inflammation and its undesirable consequences.

Modulating Effects of the Hydroethanolic Leaf Extract of Persicaria lanigera R. Br. Soják (Polygonaceae) against Acute Inflammation.

Plant species have been used traditionally to treat numerous inflammatory disorders because of their known medicinal properties. This study aimed to assess the anti-inflammatory effect of aqueous ethanolic leaf extract of Persicaria lanigera using acute inflammatory models. The safety profile of the Persicaria lanigera extract was assessed using an acute toxicity model. The anti-inflammatory effect of the Persicaria lanigera leaf extract (100-600 mg·kg-1, p.o.) was studied in carrageenan-induced paw oedema, zymosan-induced knee joint arthritis, and histamine-induced paw oedema in Sprague-Dawley rats (n = 5). It was observed that the Persicaria lanigera leaf extract administered prophylactically significantly inhibited paw oedema from 99.01 ± 12.59 to 59.10 ± 4.94%, 56.08 ± 3.65%, and 48.62 ± 3.27% at 100 mg·kg-1, 300 mg·kg-1, and 600 mg·kg-1, while the standard drug, aspirin, showed 41.84 ± 9.25% in carrageenan-induced paw oedema, respectively. Furthermore, the extract decreased knee joint inflammation significantly from 62.43 ± 5.73% to 32.07 ± 2.98% and 24.33 ± 8.58% at 300 mg·kg-1 and 600 mg·kg-1 in zymosan-induced knee joint inflammation, respectively. In the histamine-induced paw oedema model, the extract significantly inhibited oedema to 61.53 ± 9.17%, 54.21 ± 9.38%, and 54.22 ± 9.37% at the same doses. Aqueous ethanolic leaf extract of Persicaria lanigera is safe and attenuates inflammation in acute inflammation models.

Evaluation of the anti-inflammatory, analgesic, anti-pyretic and anti-ulcerogenic potentials of synthetic indole derivatives.

A large number of new synthetic compounds are synthesized in the field of heterocyclic chemistry having a variety of biological potentials. In the present study, some synthetic indole derivatives are used to check anti-inflammatory, analgesic, antipyretic and gastroprotective activity in albino mice. Albino mice of either sex of reproductive age were used for each study (n = 5). In anti-inflammatory activity, the negative control (NC) and positive control group animals were treated with normal saline and 10 mg/kg of indomethacin respectively. The treated groups received the twenty four different synthetic chemicals, after 30 min of sub cutaneous injection of carrageenan. In analgesic activity, hot-plate method is used and for each group the latency period was recorded at zero moment of the provision of required dose and after 30, 60, 90, 120 and 180 min. In anti-pyretic activity, Pyrexia was induced by using Brewer's yeast method. Before any treatment and then after duration of 18 h, the rectal temperatures were recorded. Among all the chemicals, only those chemicals which show any potential related to above mentioned activities were selected for gastroprotective activity. The gastroprotective activity was performed to check the gastric ulcers by using 300 mg/kg of single oral dose of indomethacin to animals of all groups except NC group. This study helped to screen out the most potent indole derivatives 3a-II and 4a-II from the 24 synthetic indole derivatives which demonstrated the best biological potential (anti-inflammatory, analgesic, antipyretic, and gastroprotection) as compared to the remaining ones. The micrometric and biochemical results also support the histological findings. Out of the twenty-four novel indole amines tested, 3a-II and 4a-II have shown the effective pharmacological capacity and additionally have not shown any overt and systemic toxicity. Thus these two indole amines need further in-depth pharmacokinetic and pharmacodynamics studies before they are recommended for any pre-clinical trial.

Antinociceptive and anti-inflammatory activity of DW-1021, the ionic complex of pelubiprofen and tramadol, in rodents.

Although drugs such as acetaminophen, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs), are commonly used for pain management, the side effects of these drugs such as hepatotoxicity, nephrotoxicity, nausea, and vomiting, can not be neglected. Therefore, combinations of analgesics with different mechanisms raise the possibility of developing novel analgesics. Therefore, the aim of the present study was to evaluate whether DW-1021, the ionic complex of pelubiprofen (NSAID) and tramadol (opioid), has synergic antinociceptive and anti-inflammatory effects in nociceptive as well as inflammation-induced nociceptive models compared to pelubiprofen- or tramadol-only administration. Strong synergistic antinociceptive efficacy of DW-1021 was observed in the mouse writhing test and von Frey paw withdrawal threshold test in the carrageenan-induced rats. The hot plate test in mice and the Randall-Selitto mechanical paw pressure test in carrageenan-induced rats revealed that DW-1021 had a preferable effect on relieving pain to pelubiprofen, but not as much as tramadol. In the carrageenan-induced rats, DW-1021 had a more potent effect on reducing paw inflammation (paw volume, width, and thickness) via the suppression of PGE2 production than tramadol, but less than that of pelubiprofen. Taken together, our results suggest that the administration of DW-1021, a combination of pelubiprofen and tramadol, exerted a potent effect and can be used as a potential therapeutic agent for relieving pain and inflammation.

κ-Selenocarrageenan Oligosaccharides Prepared by Deep-Sea Enzyme Alleviate Inflammatory Responses and Modulate Gut Microbiota in Ulcerative Colitis Mice.

κ-Selenocarrageenan (KSC) is an organic selenium (Se) polysaccharide. There has been no report of an enzyme that can degrade κ-selenocarrageenan to κ-selenocarrageenan oligosaccharides (KSCOs). This study explored an enzyme, κ-selenocarrageenase (SeCar), from deep-sea bacteria and produced heterologously in Escherichia coli, which degraded KSC to KSCOs. Chemical and spectroscopic analyses demonstrated that purified KSCOs in hydrolysates were composed mainly of selenium-galactobiose. Organic selenium foods through dietary supplementation could help regulate inflammatory bowel diseases (IBD). This study discussed the effects of KSCOs on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57BL/6 mice. The results showed that KSCOs alleviated the symptoms of UC and suppressed colonic inflammation by reducing the activity of myeloperoxidase (MPO) and regulating the unbalanced secretion of inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10). Furthermore, KSCOs treatment regulated the composition of gut microbiota, enriched the genera Bifidobacterium, Lachnospiraceae_NK4A136_group and Ruminococcus and inhibited Dubosiella, Turicibacter and Romboutsia. These findings proved that KSCOs obtained by enzymatic degradation could be utilized to prevent or treat UC.

Protective effect of soloxolone derivatives in carrageenan- and LPS-driven acute inflammation: Pharmacological profiling and their effects on key inflammation-related processes.

The anti-inflammatory potential of three cyanoenone-containing triterpenoids, including soloxolone methyl (SM), soloxolone (S) and its novel derivative bearing at the C-30 amidoxime moiety (SAO), was studied in murine models of acute inflammation. It was found that the compounds effectively suppressed the development of carrageenan-induced paw edema and peritonitis as well as lipopolysaccharide (LPS)-driven acute lung injury (ALI) with therapeutic outcomes comparable with that of the reference drugs indomethacin and dexamethasone. Non-immunogenic carrageenan-stimulated inflammation was more sensitive to the transformation of C-30 of SM compared with immunogenic LPS-induced inflammation: the anti-inflammatory properties of the studied compounds against carrageenan-induced paw edema and peritonitis decreased in the order of SAO > S > > SM, whereas the efficiency of these triterpenoids against LPS-driven ALI was similar (SAO ≈ S ≈ SM). Further studies demonstrated that soloxolone derivatives significantly inhibited a range of immune-related processes, including granulocyte influx and the expression of key pro-inflammatory cytokines and chemokines in the inflamed sites as well as the functional activity of macrophages. Moreover, SM was found to prevent inflammation-associated apoptosis of A549 pneumocytes and effectively inhibited the protease activity of thrombin (IC50 = 10.3 µM) tightly associated with rodent inflammatome. Taken together, our findings demonstrate that soloxolone derivatives can be considered as novel promising anti-inflammatory drug candidates with multi-targeted mechanism of action.

Synergistic Effect of Silk Sericin and Curcumin to Treat an Inflammatory Condition.

Inflammation-related diseases are recognized as the major cause of morbidity around the globe. In this study, the anti-inflammatory potential of sericin, curcumin, and their mixture was investigated in vivo and in vitro. Edema was induced via 1% carrageenan and then sericin (0.03, 0.06, 0.09 mg/ml), curcumin (1%, 2%, 3%), and their mixture doses were applied topically. The paw circumference and thickness were measured after 1-, 2-, 3-, 4-, 5-, and 6-hour post-carrageenan injection. The levels of IL-4 and IL-10 were measured from the serum. In mice fibroblast cells, sericin (20, 40, 60 µg/ml), curcumin (5, 10, 20 µM), and mixture concentrations were applied and then stimulated with lipopolysaccharide (LPS). Afterward, the cells were used for the analysis of gene expression, and the supernatant was collected for protein expression of IL-1ß, IL-4, and IL-10. Our results demonstrated that sericin and curcumin caused a dose-dependent reduction in edema, whereas the mixture-treated group reduced the paw thickness and circumference most significantly (p = .0001). Furthermore, the mixture treatment of carrageenan-inflicted group increased the levels of anti-inflammatory cytokines, IL-4 (650.87 pg/ml) and IL-10 (183.14 pg/ml), in comparison to the carrageenan control. The in vitro data revealed that among all the treatment doses, the mixture-treated group has effectively reduced the gene (1.13-fold) and protein (51.9 pg/ml) expression of IL-1ß in comparison to McCoy cells stimulated with LPS. Moreover, mixture treatment elevated the expression of IL-4 and IL-10 at genes (4.3-fold and 3.7-fold, respectively) and protein levels (169.33 and 141.83 pg/ml, respectively). The current study reports the enhanced anti-inflammatory effects of the mixture of curcumin and sericin through modulating expressions of interleukins in vitro and in vivo. Thus, natural products (curcumin and sericin)-based formulations have greater potential for clinical investigations.

Nipecotic Acid Derivatives as Potent Agents against Neurodegeneration: A Preliminary Study.

Alzheimer's Disease (AD) is a common neurodegenerative disorder characterized by memory loss and cognitive impairment. Its pathology has not been fully clarified and therefore highly effective treatments have not been obtained yet. Almost all the current treatment options aim to alleviate only the symptoms and not to eliminate the disease itself. Acetylcholinesterase inhibitors are the main therapeutic agents against AD, whereas oxidative stress and inflammation have been found to be of great significance for the development and progression of neurodegeneration. In this work, ethyl nipecotate (ethyl-piperidine-3-carboxylate), a heterocyclic carboxylic acid derivative, which acts as a GABA reuptake inhibitor and has been used in research for diseases involving GABAergic neurotransmission dysfunction, was amidated with various carboxylic acids bearing antioxidant and/or anti-inflammatory properties (e.g., ferulic acid, sinapic acid, butylated hydroxycinnamic acid). Most of our compounds have significant antioxidant potency as lipid peroxidation inhibitors (IC50 as low as 20 µΜ), as oxidative protein glycation inhibitors (inhibition up to 57%), and act as DPPH reducing agents. Moreover, our compounds are moderate LOX inhibitors (up to 33% at 100 µΜ) and could reduce rat paw edema induced by carrageenan by up to 61%. Finally, some of them possessed inhibitory activity against acetylcholinesterase (IC50 as low as to 47 µΜ). Our results indicate that our compounds could have the potentiality for further optimization as multi-targeting agents directed against AD.

Beneficial interaction of pycnogenol with indomethacin in rats.

Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.

In vivo and in silico anti-inflammatory properties of the sesquiterpene valencene.

Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1ß, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.

[Pathophysiology and pharmacotherapy of benign prostatic disorders].

Men with benign prostatic hyperplasia (BPH) often experience symptoms of overactive bladder (OAB), and bladder outlet obstruction (BOO) is one of cause of BPH. It has been suggested that bladder myogenic microcontractions or micromotions may partly contribute to the development of urgency (bladder sensory (afferent) hypersensitivity) in OAB related to BOO. We have investigated the direct effects of drugs (ß3-adrenoceptor agonists, α1-adrenoceptor antagonists, PDE type5 inhibitors) on the bladder afferent function in BOO rats. In our results, almost all drugs may act on the bladder afferent function, and mirabegron inhibits the afferent activities through the suppression of the bladder myogenic microcontractions in BOO condition. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) causes long-standing pain and/or storage symptoms including storage symptoms, such as urgency and frequency. We evaluated the likelihood of deterioration of bladder sensation in a carrageenan-induced CP/CPPS model. In results, the carrageenan-induced CP/CPPS rat model showed edema, ischemia, and inflammatory pain in the prostate, whereas a little change was detected in bladder sensation. These findings demonstrated that the bladder sensation is unlikely deteriorated in this model, suggesting CP/CPPS is possibly overlapping with symptoms in BPH.

Application of Box-Behnken design for optimization of phenolics extraction from Leontodon hispidulus in relation to its antioxidant, anti-inflammatory and cytotoxic activities.

To the best of our knowledge, there have been no phytochemical studies concerning the wild plant Leontodon hispidulus Boiss. (Asteraceae). Optimization of the green extraction process of the plant aerial parts, identification of main phenolic compounds, evaluation of antioxidant, anti-inflammatory and anticancer activities of the optimized extract have been carried out. HPLC-analysis was performed using 95% ethanolic extract. 3-Level Box-Behnken Design was applied for optimization of extraction yield and total phenolic content using 3-factors (ethanol/water ratio, material/solvent ratio and extraction time). Antioxidant, anticancer and anti-inflammatory activities were evaluated by ABTS-assay, prostate and cervical carcinoma human cell lines and carrageenan-induced rat paw edema model, respectively. HPLC-analysis showed the presence of quercetin, rutin, kaempferol, chlorogenic and ρ-coumaric acids. Increasing both ethanol/water ratio and material/solvent ratio decreased the yield, while, it increased by prolongation of the extraction time. High material/solvent ratio increased the phenolic content. The optimized extract showed high total phenolic content (104.18 µg/mg) using 201 ml of 74.5% ethanol/water at 72 h and good biological activities. Antioxidant activity was found to be 41.89 mg Trolox-equivalent/gm, with 80% free radicals inhibition. For anti-inflammatory activity, 100 mg/kg of the extract inhibited the edema in rats by 83.5% after 4 h of carrageenan injection as compared to 81.7% inhibition by indomethacin. Prostate carcinoma cell line was more sensitive to the anticancer activity of the extract than cervical carcinoma cell line (IC50 = 16.5 and 23 µg/ml, respectively). The developed extraction procedure proved to be efficient in enriching the extract with phenolic compounds with promising anticancer, anti-inflammatory and antioxidant activities.

Computer-aided discovery of pleiotropic effects: Anti-inflammatory action of dithioloquinolinethiones as a case study.

Most of pharmaceutical agents exhibit several or even many biological activities. It is clear that testing even one compound for thousands of biological activities is a practically not feasible task. Therefore, computer-aided prediction is the method-of-the-choice to select the most promising bioassays for particular compounds. Using PASS Online software, we determined the likely anti-inflammatory action of the 13 dithioloquinolinethione derivatives with antimicrobial activities. Chemical similarity search in the Cortellis Drug Discovery Intelligence database did not reveal close structural analogues with anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds was comparable with or higher than the reference drug Indomethacin. Thus, based on the in silico predictions, novel class of the anti-inflammatory agents was discovered.

Cassia artemisiodes attenuates nociceptive and diabetes-induced neuropathic pain modalities apropos antioxidant and anti-inflammatory mechanisms.

Cassia plants have a considerable position in conventional systems of medicine. The possible anti-nociceptive, anti-inflammatory, and anti-neuropathic properties of Cassia artemisiodes (CAD) extract were tested using the standard animal models. In this study, in vitro antioxidant, cyclooxygenase (COX-1 and 2), and 5-lipoxygenase (5-LOX) inhibitory assays were performed. The anti-inflammatory activity was evaluated using carrageenan, histamine, and serotonin-induced paw edema models. Antipyretic activity, thermally and chemically-induced nociception, and naloxone antagonistic activities were carried out. The CAD extract was tested for anti-neuropathic activity in the streptozotocin-induced diabetic neuropathy model. Suppressing the effect of CAD extract on the mRNA level of inducible nitric oxide synthase (iNOS), COX-2, and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) was determined by performing RT-PCR. The CAD extract inhibited COX-2 and 5-LOX enzymes, paw inflammation, and reduced nociceptive behaviors. The mRNA gene expression of iNOS, COX-2, and inflammatory cytokines was reduced significantly with increased DPPH scavenging activity. The extract significantly reduced the diabetes-induced neuropathic pain. In a nutshell, these results recommended that the CAD extract has anti-nociceptive and anti-neuropathic activities due to inhibition of inflammatory and oxidative signaling.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents.

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1ß level was assessed in the chronic model. One-way ANOVA (post hoc Tukey's) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin's anti-inflammatory effects were associated with a significant IL-1ß decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

Thymus algeriensis and Artemisia herba-alba Essential Oils: Chemical Analysis, Antioxidant Potential and In Vivo Anti-Inflammatory, Analgesic Activities, and Acute Toxicity.

The study of bioactive molecules of natural origin is a focus of current research. Thymus algeriensis and Artemisia herba-alba are two medicinal plants widely used by the Moroccan population in the traditional treatment of several pathologies linked to inflammation. This study aimed to evaluate the single and combined antioxidant, anti-inflammatory and analgesic effects of the essential oils extracted from these two medicinal plants, and also their potential toxicity. Essential oils were extracted using hydro-distillation in a Clevenger-type apparatus. The antioxidant activity was evaluated by two methods: the scavenging of the free radical DPPH, and the reduction in iron. Anti-inflammatory activity was evaluated by evaluating the edema development induced by carrageenan injecting, while the analgesic power was evaluated according to the number of abdominal contortions induced by the intraperitoneal injection of acetic acid (0.7%). The acute oral toxicity was performed to assess the potential toxicity of the studied EOs, followed by an analysis of the blood biochemical parameters. The results of the two antioxidant tests indicated that our extract mixture exhibits good iron reduction capacity and very interesting DPPH free radical scavenging power, with an IC50 of around 4.38 ± 0.98 µg/mL higher than that of the benchmark antioxidant, BHT. The anti-inflammatory test demonstrated that the mixture administered orally at a dose of 150 mg/kg has a better activity, exceeding that of 1% Diclofenac, with a percentage of maximum inhibition of the edema of 89.99 ± 4.08. The number of cramps in the mice treated with the mixture at a dose of 150 mg/kg is significantly lower (29.80 ± 1.92) than those of the group treated with Tramadol (42.00 ± 2.70), respectively. The toxicity results show no signs of toxicity with an LD50 greater than 150 mg/Kg. These interesting results show that the two plants' EOs had an important anti-inflammatory, analgesic, and antioxidant activity, and also a powerful synergistic effect, which encourages further in-depth investigations on their pharmacological proprieties.

Analysis on the effect of intravenous anesthesia with dexmedetomidine and propofol combined with seaweed polysaccharides on hemodynamics and analgesia in pregnant females undergoing painless induced abortion.

This study attempted to investigate the effect of intravenous anesthesia with dexmedetomidine and propofol combined with seaweed polysaccharides on painless induced abortion. A total of 82 pregnant females were divided into study group and reference group. The subjects in the study group took seaweed polysaccharides orally before surgery and received intravenous anesthesia with dexmedetomidine and propofol, while the subjects in the reference group received intravenous anesthesia with sufentanil combined with propofol. The onset time of anesthesia in the reference group was significantly shorter than that in the study group (P<0.001) and both recovery time and the dosage of propofol in the study group were significantly lower than those in the reference group (P<0.001). The values of MAP and HR at T3 and T4, clinical analgesia effective rate, ramsay sedation scores and incidence of adverse reactions of the subjects in study group was significantly better than those indexes of the subjects in reference group (P<0.05). The intravenous anesthesia with dexmedetomidine and propofol combined with seaweed polysaccharides is a promising strategy for painless induced abortion, which is worthy of application and popularization in clinical practice.