In Vivo Neuropharmacological Effects of Neophytadiene.

Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

Postoperative administration of ketorolac compared to other drugs for pain control after third molar surgery: A meta-analysis of double-blind, randomized, clinical trials.

AIMS: The aim of this study was to evaluate the analgesic effectiveness and adverse reactions of ketorolac in comparison with other drugs when administered postoperatively after third molar surgery. METHODS: PubMed and Google Scholar were utilized to search for articles comparing the efficacy and safety of ketorolac and other analgesic agents after third molar surgery. Data from papers with a lower risk of bias were recorded. The overall evaluation of analgesia onset, general and subgroup evaluation of the number of patients requiring rescue analgesic medication, general and subgroup assessment of the study medication (satisfaction on the study drugs), and the overall estimation of adverse effects were performed using the Review Manager Software 5.3 to analyse the data and obtain the meta-analysis plot. RESULTS: The subgroup evaluation of the study medication showed that patients who received ketorolac 30 mg were more satisfied than those who were given parecoxib 1 mg (odds ratio [OR] = 8.57, 95% confidence interval [CI] = 3.66-20.08, P = .00001), parecoxib 2 mg (OR = 7.17, 95% CI = 2.88-17.86, P = .0001), parecoxib 5 mg (OR = 3.03, 95% CI = 1.69-5.41, P = .0002), and parecoxib 10 mg (OR = 2.42, 95% CI = 1.36-4.32, P = .003). Moreover, patients who received ketorolac reported fewer adverse reactions compared with those who had received opioid analgesics (OR = 0.14, 95% CI = 0.32-1.76, P = .0001). CONCLUSIONS: The data from this study demonstrates that the postoperative administration of ketorolac 30 mg presents better results on patient satisfaction when compared to parecoxib 1 mg to 10 mg, and presents a similar satisfaction to parecoxib 20 mg following third molar removal.

A meta-analysis on the efficacy of the ropivacaine infiltration in comparison with other dental anesthetics.

OBJECTIVES: The aim of this meta-analysis was to assess the clinical efficacy and safety profile of ropivacaine in comparison with other dental anesthetics in different clinical conditions. MATERIALS AND METHODS: This meta-analysis was registered in the National Institute for Health Research PROSPERO (ID: CRD42020205580). PubMed and Scholar Google were consulted to identify clinical trials using ropivacaine in comparison with other local anesthetic drugs for any dental procedure. Articles comparing ropivacaine and other dental anesthetics were assessed with the Cochrane Collaboration's risk of bias tool. Data from reports without a high risk of bias were extracted (anesthetic and adverse effects) and analyzed using the Review Manager Software 5.3. for Windows and the Risk Reduction Calculator. RESULTS: Ropivacaine produces a longer anesthetic time when compared with lidocaine/adrenaline (n = 260; p = 0.00001) and similar anesthesia than bupivacaine (n = 190). CONCLUSIONS: Data of this study indicate that ropivacaine infiltration produces a longer anesthetic time when compared with lidocaine and articaine but not when compared to bupivacaine in dental procedures. CLINICAL RELEVANCE: Ropivacaine was more effective than lidocaine for dental anesthesia. For this reason, the manufacture of a ropivacaine dental cartridge with a suitable concentration could be an important advancement for clinical practice.

Antinociceptive and anti-inflammatory effects of Cuphea aequipetala Cav (Lythraceae).

Cuphea aequipetala Cav (Lythraceae) is an herb used in folk treatment for pain and inflammation. The aim of this study was to evaluate the antinociceptive and anti-inflammatory actions of an ethanol extract from the leaves and stem of Cuphea aequipetala (CAE). The antinociceptive actions of CAE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing, hot plate, and formalin tests. The possible mechanism of action of CAE was evaluated using inhibitors. The effects of CAE on motor coordination were assessed by the rotarod test. The in vitro anti-inflammatory actions of CAE were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed by the TPA-induced ear oedema and the carrageenan-induced paw oedema tests. The production of inflammatory mediators was estimated from both in vitro and in vivo assays. CAE showed antinociception (ED50 = 90 mg/kg) in the acetic acid test and in the second phase of the formalin test (ED50 = 158 mg/kg). Pretreatment with glibenclamide or L-NAME partially reversed the antinociception shown by the plant extract. CAE (50-200 mg/kg) did not affect motor coordination in mice. CAE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 10 pg/ml) and, in the carrageenan-induced paw oedema test (threefold increase). In conclusion, CAE induced antinociceptive effects without affecting motor coordination, probably due to the involvement of nitric oxide and ATP-sensitive K+ channels. CAE also exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.

Use of allopathic and complementary medicine for preventing SARS-CoV-2 infection in Mexican adults: A national survey.

BACKGROUND: The aim of this study was to assess the frequency of allopathic and complementary medicine use for preventing the infection with SARS-CoV-2 in Mexico. A descriptive and cross-sectional study was conducted using an online questionnaire among general adult population (n = 16,724) of the 32 Mexican states from March to November 2020. METHODS: The factors associated with the use, self-medication practice, and adverse reactions due the consumption of allopathic and complementary medicine to prevent infection with SARS-CoV-2 virus were assessed using a structured questionnaire. The suspected adverse reactions associated with the use of drugs or complementary medicine were reported. RESULTS: The prevalence (42.9%) of allopathic and/or complementary medicine use for preventing SARS-CoV-2 infection was mainly associated with unemployment [OR:2.026 (1.722-2.283)]. Acetaminophen (n = 2272) and vitamin C (n = 3252) were the main allopathic and complementary medicine products used to prevent SARS-CoV-2 infection, respectively. The prevalence of self-medication and adverse reactions was 35.3% and 4.8%, respectively. Self-medication [OR:1.930 (1.633-2.282)] and adverse reactions [OR:2.603 (2.015-3.363)] were mainly associated with individuals of low socioeconomic status. Hydroxychloroquine (21.2%) and chloroquine (15.2%) showed the highest prevalence of adverse reactions, which were mainly related to gastrointestinal disorders. CONCLUSION: The use of medications and complementary medicine to prevent SARS-CoV-2 infection is prevalent (almost one-half of the respondents) among Mexican population, and it is mainly associated with unemployment. Self-medication and the adverse reactions derived from self-medication are also prevalent and seem to be influenced by low socioeconomic status.

Enantioselective synthesis of tetrahydrocarbazoles via trienamine catalysis and their anxiolytic-like activity.

The first study about the anxiolytic activity of two chiral tetrahydrocarbazoles is presented. This new chiral compounds were prepared through an organocatalytic strategy via trienamine activation. The in situ ortho-quinodimethane species, formed by the condensation of the N-protected 2-methylindole acrylaldehyde with a sterically hindred diarylsilylprolinol ether derivative as catalyst, easily participate in a Diels-Alder reaction with the ethyl cyanophenyl acrylate as dienophile, in good yields and excellent stereoselectivity. These compounds showed activity against anxiety and mood disorders that can possibly contribute in the discovery of new drugs. In addition, the use of N-protected 2-methylindole acrylaldehyde will set a new base for the synthesis of medically and pharmacologically important tetrahydrocarbazoles via trienamine catalysis.

Central nervous system evaluation of an ethanol extract of Bidens odorata Cav (Asteraceae) leaves, and its antinociceptive interaction with paracetamol and naproxen.

INTRODUCTION: Bidens odorata Cav (Asteraceae) is a medicinal plant employed for the treatment of pain, anxiety, and depression. This study aimed to evaluate some neuropharmacological effects of an ethanol extract of B. odorata (BOE) and assess its antinociceptive interaction with naproxen and paracetamol. MATERIALS AND METHODS: The following neuropharmacological effects were evaluated with the ethanolic extract of B. odorata leaves (BOE) (10-200 mg/kg p.o.): the strychnine-induced-convulsion assay (anticonvulsant effect), rotarod test (locomotor activity), tail suspension test (anti-depressant-like activity), cylinder exploratory test (anxiolytic-like actions), and pentobarbital-induced sleep test (sedative effect). The interaction of the BOE-paracetamol and BOE-naproxen combinations were evaluated with the acetic acid-induced writhing test. The ED50 value of each drug was estimated and the combinations of paracetamol and naproxen with BOE were calculated. RESULTS: BOE (100-200 mg/kg) showed anti-convulsant activity by increasing the latency to occurrence of strychnine-induced convulsions, antidepressant-like effects by 28% and 33%, respectively, exerted anxiolytic actions (ED50 = 125 mg/kg), but did not affect motor locomotion. The pre-treatment with 2 mg/kg flumazenil or 20 mg/kg pentylenetetrazol partially reverted the anxiolytic activity shown by BOE alone. BOE (200 mg/kg) prolonged the duration of sleep with similar effect in comparison to clonazepam (1.5 mg/kg). The combinations of BOE-paracetamol (1:1) and BOE-naproxen (1:1) showed antinociceptive synergism. CONCLUSION: BOE induces sedative and anticonvulsant effects. The anxiolytic actions shown by BOE are probably induced by the participation of the GABAergic system. BOE exerts antinociceptive synergistic interaction with paracetamol and naproxen probably by the participation of nitric oxide and ATP-sensitive K+ channels, respectively.

Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro, In Vivo, and In Silico Approaches.

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC50 of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD50 value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD50 was LD50 > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.

Anti-inflammatory and antinociceptive effects of an ethanol extract from Senna septemtrionalis.

Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a medicinal plant used as a folk remedy for inflammation and pain. The objective of this study was to evaluate the anti-inflammatory and antinociceptive actions of an ethanol extract of Senna septemtrionalis aerial parts (SSE). The in vitro anti-inflammatory effects of SSE were assessed using LPS-stimulated macrophages and the subsequent quantification of the levels of cytokines (IL-6, IL-1ß, and TNF-α) with ELISA kits, nitric oxide (NO), and hydrogen peroxide (H2O2). The in vivo anti-inflammatory actions of SSE were evaluated with the TPA-induced ear oedema test and the carrageenan-induced paw oedema test. The antinociceptive actions of SSE (10-200 mg/kg p.o.) were assessed using three models: two chemical assays (formalin-induced orofacial pain and acetic acid-induced visceral pain) and one thermal assay (hot plate). SSE showed in vitro anti-inflammatory actions with IC50 values calculated as follows: 163.3 µg/ml (IL-6), 154.7 µg/ml (H2O2) and > 200 µg/ml (IL-1ß, TNF-α, and NO). SSE showed also in vivo anti-inflammatory actions in the TPA test (40% of inhibition of ear oedema) and the carrageenan test (ED50 = 137.8 mg/kg p.o.). SSE induced antinociceptive activity in the formalin orofacial pain test (ED50 = 80.1 mg/kg) and the acetic acid-induced writhing test (ED50 = 110 mg/kg). SSE showed no antinociceptive actions in the hot plate assay. The pre-treatment with glibenclamide abolished the antinociceptive action shown by SSE alone. Overall, SSE exerted in vitro and in vivo anti-inflammatory actions, and in vivo antinociceptive effects by the possible involvement of ATP-sensitive K + channels.

Anti-inflammatory and diuretic effects of the diterpene ent-dihydrotucumanoic acid.

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent-dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti-inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti-inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ-carrageenan-induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 µg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500-1,000 µg/mL showed moderate genotoxicity. In LPS-stimulated macrophages, DTA showed IC50 values of 74.85 µg/mL (TNF-α) and 58.12 µg/mL (NO), whereas the maximum inhibition of IL-6 (24%) and IL-1ß (36%) was recorded at 200 µg/mL. DTA induced in vivo anti-inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti-inflammatory activity of DTA seems to be associated with the decrease in the release of TNF-α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L-NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti-inflammatory and diuretic effects, but lacked antioxidant effects.

Protecting-Group-Free Total Synthesis and Biological Evaluation of 3-Methylkealiiquinone and Structural Analogues.

The modular protecting-group-free total synthesis of 3-methylkealiiquinone, an analogue of the marine alkaloid kealiiquinone, was accomplished in seven steps. A regioselectively constructed functionalized arylbenzimidazolone moiety and dimethyl squarate were used as the only two building blocks. A thermal ring expansion via 6π-conrotatory ring closure to build the quinone fragment gave rise to the desired linear analogue of the natural compound along with a nondescribed structurally attractive angular naphtho[1,2- d]imidazole regioisomer. The IC50 values for the compounds were determined on three cancer cell lines.

Antinociceptive, anti-inflammatory, and central nervous system (CNS) effects of the natural coumarin soulattrolide.

Soulattrolide is a natural coumarin synthesized by the leaves of species of Calophyllum (Calophyllaceae) rain forest trees, including the American C. brasiliense, and the Asian C. teysmanii. Soulattrolide is a potent inhibitor of the reverse transcriptase from HIV-1 (RT-HIV-1), and active against Mycobacterium tuberculosis. However, the effects of this coumarins on other systems, remains to be evaluated. C. brasiliense is used in traditional medicine for the treatment of pain and inflammation. Therefore, we decided to explore the antinociceptive, anti-inflammatory activity of soulattrolide in mice, as well as, some of its possible effects on the CNS. Soulattrolide showed antinociceptive effects in the writhing test (ED50 = 33.8 mg/kg), as well as, in the formalin test with an ED50 = 7.9, and 22.1 mg/kg for Phases 1 and 2, respectively. The highest dose of soulattrolide (50 mg/kg) induced 40% of antinociception in the hot plate test. Regarding to anti-inflammatory activity, in the 12-O-Tetradecanoylphorbol-13-acetate (TPA) test, soulattrolide showed an IC50 = 1.81 µmol/ear, whereas in the myeloperoxidase assay, it showed an inhibition of 87% (1 µmol/ear). Soulattrolide showed sedative effects on the pentobarbital-induced sleeping time test, and the rotarod test, but lacked antidepressant activity on the tail suspension test. In conclusion, we report for the first time, the antinociceptive effects of soulattrolide in mice, like those of naproxen; soulattrolide also showed mild anti-inflammatory activity, as well as mild sedative and anxiolytic properties, therefore, it has also activity on the CNS.

Anti-inflammatory and antinociceptive effects of tilifodiolide, isolated from Salvia tiliifolia Vahl (Lamiaceae).

Salvia tiliifolia Vahl (Lamiaceae) is used for the empirical treatment of pain and inflammation. The diterpenoid tilifodiolide (TFD) was isolated from Salvia tiliifolia. The in vitro anti-inflammatory effects of TFD (0.1-200 µM) were assessed using murine macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The in vivo anti-inflammatory activity of TFD was assessed using the carrageenan-induced paw edema test for 6 h. The antinociceptive effects of TFD were evaluated using the formalin test and the acetic acid induced-writhing test. The effects of TFD on locomotor activity were assessed using the open field test and the rotarod test. TFD inhibited the production of TNF-α (IC50 = 5.66 µM) and IL-6 (IC50 = 1.21 µM) in macrophages. TFD (200 mg/kg) showed anti-inflammatory effects with similar activity compared to 10 mg/kg indomethacin. The administration of TFD induced antinociception in the phase 1 (ED50 = 48.2 mg/kg) and the phase 2 (ED50 = 28.9 mg/kg) of the formalin test. In the acetic acid assay, TFD showed antinociceptive effects (ED50 = 32.3 mg/kg) with similar potency compared to naproxen (ED50 = 36.2 mg/kg). In the presence of different inhibitors in the acetic acid assay, only the co-administration of TFD and naloxone reverted the antinociceptive activity shown by TFD alone. TFD did not affect locomotor activity in mice. TFD exerts in vitro and in vivo anti-inflammatory activity and in vivo antinociceptive effects.

Self-medication practice in pregnant women from central Mexico.

Self-medication during pregnancy represents a serious threat for mother and child health. The objective of this study was to evaluate the prevalence and the factors associated with self-medication among Mexican women living in the central region of Mexico. This is a descriptive interview-study of 1798 pregnant women or women who were pregnant no more than 3 years ago, when the interview was carried out. Data analysis was carried out with chi-square analysis and odds ratio. The prevalence of self-medication (allopathic drugs, medicinal plants, and other products, including vitamins, food supplements, among others) was 21.9%. The factors associated (p < 0.05) with self-medication were: higher education (college and postgraduate), smoking, and consumption of alcohol. Smoking was the strongest factor (OR: 2.536; 1.46-4.42) associated to self-medication during pregnancy, followed by consumption of alcohol (OR: 2.06; 1.38-3.08), and higher education (OR: 1.607; 1.18-2.19). Medicinal plant consumption was associated with nausea, constipation, migraine, and cold (p < 0.05), whereas he self-medication of allopathy was associated with gastritis and migraine (p < 0.05). Self-medication was influenced mainly by a relative or friend, who recommended the use of herbal medicine/allopathic medication. Two of the most common medicinal plants (arnica and ruda) here informed are reported to induce abortion or toxicity during pregnancy. The findings showed that self-medication (medicinal plants and allopathic medication) is a common practice among pregnant women from central Mexico. Adequate counselling of pregnant women by healthcare professionals about the potential risks of self-medication with herbal medicine and allopathic drugs during pregnancy is strongly warranted.

Synergism between Naproxen and Rutin in a Mouse Model of Visceral Pain.

Preclinical Research The aim of the present study was to evaluate the antinociceptive interaction between naproxen and the glycoside flavonoid, rutin in the acetic acid-induced writhing test in mice. Naproxen (5, 20, 50, and 100 mg/kg p.o.) or rutin (10, 25, 50, and 100mg/kg p.o.) were administered 60 min before the intraperitoneal administration with acetic acid. The dose-response curve of each individual compound and the experimental effective dose 50 (ED50 ) value were obtained to determinate different proportions of the combinations between the two compounds (naproxen-rutin 1:1, 3:1, and 3:1) in the writhing test. The results indicated a synergistic antinociceptive interaction between two drugs with different mechanism of action, naproxen and rutin in all the combinations. Drug Dev Res 78 : 184-188, 2017. © 2017 Wiley Periodicals, Inc.

Antinociceptive Activity of Ent-Dihydrotucumanoic Acid Isolated from Gymnosperma glutinosum Spreng Less.

Preclinical Research The diterpene ent-dihydrotumanoic acid (DTA) was among the compounds isolated from Gymnosperma glutinosum (Spreng) Less (Asteraceae). There are no reports regarding the pharmacological effects of DTA. Cytotoxicity against cancer cells (1-250 µM), and the antibacterial (50-1400 µM) activity of DTA were evaluated using the MTT assay, and the minimum inhibitory concentration test, respectively. The antidiarrheal (1-100 mg/kg p.o.) and anti-inflammatory (2 mg/ear) effects of DTA were evaluated using castor oil and 12-O-tetradecanoylphorbol-13-acetate, respectively. The antinociceptive and sedative effects of DTA (1-100 mg/kg p.o.) were evaluated using two models of chemically-induced nociception, and the pentobarbital-induced sleeping time test, respectively. The antinociceptive mechanism of DTA was evaluated using the acetic acid writhing test with inhibitors related to pain processing pathways. The effects of DTA (10-100 mg/kg p.o.) on locomotor activity were evaluated using the rotarod test. DTA lacked cytotoxic activity (IC50 > 100 µM) on cancer cells, possessed moderate antibacterial effects against B. subtillis (MIC= 175 µM), moderate antidiarrheal and anti-inflammatory effects, and minimal vasorelaxant effects. In the formalin test, DTA showed antinociceptive effects in both phases. In the acetic acid test, DTA showed antinociceptive activity (ED50 = 50.2 ± 5.6 mg/kg) with potency similar to that of naproxen (NPX; ED50 =33.7 ± 4.5 mg/kg) an effect blocked by naloxone implicating an opioid mechanism. DTA also exerted antidiarrheal activity and showed no sedative effects or changes in locomotor activity in mice. Drug Dev Res 78 : 340-348, 2017. © 2017 Wiley Periodicals, Inc.

Pharmacological evaluation of 2-angeloyl ent-dihydrotucumanoic acid.

CONTEXT: Gymnosperma glutinosum (Spreng.) Less. (Asteraceae) is a bush used for the empirical treatment of pain, fever, and cancer. An ent-neo-clerodane diterpene (2-angeloyl ent-dihydrotumanoic acid; ADTA) was isolated from G. glutinosum. OBJECTIVE: This study evaluates the cytotoxic, anti-inflammatory, and antinociceptive effects of ADTA. MATERIALS AND METHODS: The cytotoxic effects of ADTA (1-350 µM) were evaluated using the MTT assay with human tumorigenic (SW-620, MDA-MB231, SKLU1, SiHa, and PC-3), and non-tumorigenic (HaCaT) cells for 48 h. The in vitro anti-inflammatory effects of ADTA (0.23-460 µM) were assessed using murine peritoneal macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The antinociceptive effects of ADTA (25-100 mg/kg p.o.) were evaluated using two in vivo models of chemical-induced nociception during 1 h. RESULTS: ADTA lacked cytotoxic activity (IC50> 100 µM) on tumorigenic cells. In non-tumorigenic cells (HaCaT), ADTA exerted low cytotoxic effects (IC50 = 273 µM). ADTA, at concentrations of 115 µM or higher, decreased the release of pro-inflammatory mediators. The maximum antinociceptive effects of ADTA in the acetic acid-induced abdominal constrictions by ADTA was found at 100 mg/kg (63%), whereas in the formalin test at phase 1 and phase 2, ADTA (100 mg/kg) decreased the licking time by 47 and 71%, respectively. CONCLUSION: The results indicate that ADTA, obtained from G. glutinosum, exerts moderate in vitro anti-inflammatory and in vivo antinociceptive effects, but lacks cytotoxic effects on human cancer cells.

Antinociceptive Activity of an Ethanol Extract of Justicia spicigera.

Preclinical Research The aim of the present study was to evaluate the antinociceptive and sedative activity of an ethanol extract of Justicia spicigera an evergreen used in Mexican traditional medicine for the relief of pain, wounds, fever and inflammation. At 200 mg/kg po, the maximum dose examined, the ethanol extract of J. spicigera (JSE) had analgesic activity in mice in the acetic acid writhing test, the second phase of the formalin test and the tail flick test that was similar in efficacy to the NSAID, naproxen (150 mg/kg po). JSE was inactive in the hot plate test and and the ketamine-induced sleeping time test; it had no sedative effects. These results show that the ethanol extract from the leaves of J. spicigera has antinociceptive effects in mice without inducing sedation. Drug Dev Res 77 : 180-186, 2016. © 2016 Wiley Periodicals, Inc.

Synthesis, antinociceptive and anti-inflammatory effects of porphyrins.

Porphyrins are natural compounds with several biological activities. We report the synthesis and the evaluation of the anti-inflammatory and antinociceptive effects of 4 porphyrins: 5,10,15,20-tetraphenylporphyrin (TPP), 5,10,15,20-tetra(4'-fluorophenyl)porphyrin (TpFPP), 5,10,15,20-tetra(4'-chlorophenyl)porphyrin (TpClPP), and 5,10,15,20-tetra(4'-bromophenyl)porphyrin (TpBrPP). The in vitro anti-inflammatory effects were evaluated on heat-induced hemolysis. The antinociceptive effects were evaluated using the hot plate and formalin tests. The in vivo anti-inflammatory assays were tested on the acute and chronic TPA (12-O-tetradecanoylphorbol 13-acetate) method to induce ear edema. The anti-arthritic effects were evaluated using carrageenan kaolin induced arthritis (CKIA). All porphyrins inhibited hemolysis with similar potency than naproxen (NPX). In the antinociceptive tests, all porphyrins tested at 200mg/kg showed similar effects compared to 100mg/kg NPX. In the in vivo anti-inflammatory acute assay, only three porphyrins (TPP, TpFPP and TpBrPP) decreased inflammation with similar activity than 2mg/ear indomethacin (IND). Further anti-inflammatory experiments were carried out with TPP, TpFPP and TpBrPP. In the in vivo anti-inflammatory chronic assay, porphyrins decreased inflammation with similar activity than 8mg/kg IND. Porphyrins tested at 200mg/kg showed anti-arthritic effects. The antinociceptive, anti-inflammatory and arthritic activities of porphyrins suggest that these compounds might be a good alternative for the treatment of inflammatory diseases.

Effects of kramecyne on LPS induced chronic inflammation and gastric ulcers.

Preclinical Research Krameria cytisoides is used for the treatment of inflammation, stomach pain, and gastric ulcers. The active ingredient from this plant is a peroxide, kramecyne (KACY) which has anti-inflammatory effects. The aim of the present study was to evaluate the anti-inflammatory activities of KACY in lipopolysaccharide (LPS)-induced systemic chronic inflammation in mice for 60 days, using dexamethasone (DEX) as the positive control, vehicle (the LPS group) as the negative control and the control group (mice without inflammation). KACY did not affect survival, body weight or relative organ weight in mice but it: decreased nitric oxide (NO) production by 68%; prostaglandin E2 (PGE2 ) by 67%; increased release of anti-inflammatory cytokine IL-10 (2.0-fold), and reduced production of the proinflammatory cytokines, IL-6 (2.0-fold), IL-1ß (2.4-fold), and TNF-α (2.0-fold). Furthermore, the gastroprotective effects of KACY in mice were evaluated in an ethanol-induced gastric ulcer model. The results showed that KACY at 50 and 100 mg/kg exerted gastroprotective effects with similar activity to 50 mg/kg ranitidine. In gastric tissues, KACY decreased the level of malondialdehyde (MDA) but increased the catalase (CAT) activity. KACY have potential for the treatment of chronic inflammatory diseases due its similar activity to that of DEX. It also has gastroprotective effects.