Tail Flick Research Articles

Formulation and Evaluation of Transdermal Gel of Ibuprofen: Use of Penetration Enhancer and Microneedle

The objective of the current study was to develop Ibuprofen (IBP) gel using different polymers individually and in combination and then to select best gel formulation based on various in-vitro evaluation parameters such as bioadhesive strength, gel strength, spreadability, viscosity and drug release study. The selected gel formulation was found to be composed of 1% (w/w) each of hydroxypropyl methylcellulose (HPMC K100M) and sodium carboxy methylcellulose (NaCMC). Two techniques such as chemical method using 1,8-cineole as chemical penetration enhancer (CPE) and physical technique using microneedle were employed to improve IBP permeation across the abdominal skin of rat. Out of the two techniques, the later technique showed higher (2.865-fold) permeation enhancement compared to control. Furthermore, a synergistic effect was also observed when both the techniques were used simultaneously with 3.307-fold increase in permeation enhancement. In-vivo anti-inflammatory study on rats induced with carrageenan paw oedema and analgesic activity investigation by tail flick method in rat model exhibited sustained effect up to 8 h compared to orally treated group. The stability study at room and accelerated conditions for three months did not show any sign of instability. Thus, the developed IBP gel is stable and have potential to illicit both anti-inflammatory and analgesic effect when administered transdermally.

Modulation of synergism COX-1 with COX-2 in the tail flick of mice

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used in the treatment of pain. In this study was evaluated, by isobolographic analysis, in a radiant heat model of mice, the tail flick, the potential antinociceptive pharmacological interaction of the combination between ketorolac and meloxicam and the modulation by tropisetron, risperidone, prazosin, yohimbine, naltrindole or 7-Nitroindazole. In the assay, the combination of ketorolac with meloxicam induces an additive interaction with an interaction index of 12.20 ± 0.92. Neither tropisetron nor risperidone nor prazosin nor yohimbine modify the nature of interaction, however naltrindole and 7-Nitroindazol change the nature of interaction from additive a subadditive with an interaction index of 16.85 ± 2.52 and 18.00 ± 2.57, respectively. The current results suggests that the interaction antinociceptive of the combination between ketorolac with meloxicam does not seem to be influenced by adrenergic, dopaminergic, histaminergic or serotonegic mechanisms. Nonetheless, the pretreatment of the mice with naltrindole or con 7-Nitroindazole induced a significant decrease in the antinociceptive power of the combination with a significant reduction in DE. It is suggested that DOR and NO may be involved, in the tail flick model, regulating the antinociceptive bioactivity of these NSAIDs.

Modulation of synergism COX-1 with COX-2 in the tail flick of mice

Modulation of synergism COX-1 with COX-2 in the tail flick of mice

Role of dopaminergic system in oxytocin analgesia: The missing part in a puzzle

Purpose: To investigate the analgesic effects of oxytocin (OT) and elucidate the role of dopaminergic system in its mechanisms.Methods: In this study, 72 male (n=6 for each group) 230-250 gr Wistar Albino rats were used. Firstly, dose studies were performed with 100 μg/kg, 200 μg/kg and 400 μg/kg to determine the optimal analgesic effect of oxytocin. Optimal dose was found at 200 μg/kg, and then animals were divided into nine groups: Saline, D1 agonist (SKF 38393; 0.1 mg/kg), D1 antagonist (SCH-23390; 0.1 mg/kg), D1 agonist + oxytocin, D1 antagonist + oxytocin, D2 agonist (Cabergoline; 0,5 mg/kg), D2 antagonist (Sulpride; 10 mg/kg), D2 agonist + oxytocin and D2 antagonist + oxytocin. Serum physiologic saline was given to the saline group and other drugs were administered intraperitoneally at the indicated doses. Tail-flick and hot-plate tests were used to measure analgesic effects. Analgesic tests were measured in 30 min-intervals (at 30th, 60th, 90th, and 120th min) and recorded in seconds. To evaluate maximum antinociceptive effect (% MPE), the tail-flick and hot-plate latencies were converted to the antinociceptive effectivenessResults: The results show that D1 antagonist SCH-23390 (0.1 mg/kg) and D2 agonist cabergoline (0.5 mg/kg) created strong analgesia while the D1 agonist SKF 38393 (0.1 mg/kg) and D2 antagonist sulpiride (10 mg/kg) did not have any analgesic effect. However, only D2 antagonist sulpiride blocked the analgesic effect produced by OTConclusion: OT may be one of the primary agents participating in spinal analgesia, and the dopaminergic system is one of the central mechanisms of action for this important molecule. The dopaminergic system may also be one of the targets for ‘descending’ analgesic system.
 Keywords: Oxytocin, Tail flick, Hot plate, Dopaminergic, Analgesic, Antagonist, Agonist

Synthesis, Characterization and Analgesic Activity of Cadmium(II) Complex of Tolfenamic Acid

Tolfenamic acid is a member of fenamate group of non-steroidal anti-inflammatory drugs (NSAID). It is generally used to treat migraine. In recent studies, metal complexes of traditional drugs like, manganese(II) complex of tolfenamic acid and mefenamic acid; cobalt(II) and zinc(II) complexes of tolfenamic acid are reported to give better biological activities than their parent drugs. In this study, tolfenamic acid was complexed with a divalent metal, cadmium(II) to form the drug-metal complex. The peripheral and central analgesic activities of this complex were tested to find out the impact of complexation on the pharmacological activity of the drug. Cadmium nitrate tetrahydrate was used for the complexation reaction and Fourier transform infrared (FT-IR) spectroscopic technique was used to identify the drug-metal complexation. Writhing method and tail flick technique were used to test peripheral and central analgesic activities, respectively in Swiss albino mice model. Comparison of the data obtained for positive and negative controls with the drug metal complex revealed a statistically significant increase in analgesic activities. Extensive experimentation is underway for further development in order to achieve better activity and assess toxicity profiles.
 Dhaka Univ. J. Pharm. Sci. 19(1): 59-64, 2020 (June)

Examining the Effects of (α4)3(β2)2 Nicotinic Acetylcholine Receptor-Selective Positive Allosteric Modulator on Acute Thermal Nociception in Rats.

Neuronal nicotinic acetylcholine receptor (nAChR)-based therapeutics are sought as a potential alternative strategy to opioids for pain management. In this study, we examine the antinociceptive effects of 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrazol-4-yl)isoxazole (CMPI), a novel positive allosteric modulator (PAM), with preferential selectivity to the low agonist sensitivity (α4)3(β2)2 nAChR and desformylflustrabromine (dFBr), a PAM for α4-containing nAChRs. We used hot plate and tail flick tests to measure the effect of dFBr and CMPI on the latency to acute thermal nociceptive responses in rats. Intraperitoneal injection of dFBr, but not CMPI, dose-dependently increased latency in the hot plate test. In the tail flick test, the effect achieved at the highest dFBr or CMPI dose tested was only <20% of the maximum possible effects reported for nicotine and other nicotinic agonists. Moreover, the coadministration of dFBr did not enhance the antinociceptive effect of a low dose of nicotine. Our results show that the direct acute effect of dFBr is superior to that for CMPI, indicating that selectivity to (α4)3(β2)2 nAChR is not advantageous in alleviating responses to acute thermal nociceptive stimulus. However, further studies are necessary to test the suitability of (α4)3(β2)2 nAChR-selective PAMs in chronic pain models.

Behavioral changes in calves 11 days after cautery disbudding: Effect of local anesthesia

Hot-iron disbudding results in painful burn wounds that take weeks to heal. Spontaneous behaviors indicative of pain are apparent in the immediate hours after disbudding, but whether they occur later in the healing process is unknown. To evaluate whether ongoing pain was present around the time the necrotic tissue loosens from the scalp, we tested the effect of administration of local anesthetic 11 d after the procedure. Disbudded female Holstein and Jersey calves (n = 24) were randomly assigned to receive an injection of local anesthetic (lidocaine) or saline at the cornual nerve on both sides of the head. We recorded the frequency of 8 behaviors for 75 min: head shakes, head rubs, head scratches, ear flicks, tail flicks, bucks/jumps/kicks, grooming, and transitions between standing and lying. Calves treated with lidocaine shook their heads less and tended to flick their ears less than calves administered saline, consistent with the effects of pain relief previously reported in the immediate hours after disbudding. These calves also rubbed their head against the sides of the pen more often, suggesting lidocaine suppressed wound protective behavior. Head shaking and head scratching became more common in the last 25 min compared with the first 50 min in calves treated with lidocaine, consistent with the return of sensation to the disbudding wounds. No treatment differences in the other behaviors were observed. These results suggest that calves experience ongoing pain 11 d after hot-iron disbudding, adding to a growing body of evidence that pain persists for weeks after the procedure.

Sex dependent alterations of resveratrol on social behaviors and nociceptive reactivity in VPA-induced autistic-like model in rats

IntroductionThe present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats. MethodsPregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively. ResultsThe results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats. ConclusionIt can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.

Antinociceptive Activity of the Essential Oil Formulation from the Roots of Saussaura lappa Clarks

Saussurea lappa Clarke (Compositae) is well known as a medicinal plant. Its roots are traditionally used in alleviating pain and swelling. In the current research, we have evaluated the antinociceptive activity of essential oil obtained from the roots of S. lappa. In addition, the development and evaluation of a pharmaceutical-grade cream was also conducted in this study. Extraction of essential oil from the roots of the plant was performed by a steam distillation method using the Clevenger apparatus. The antinociceptive activity was assessed in Sprague Dawley rats using tail flick, hot plate, and analgesic-meter, where diclofenac was used as a standard reference analgesic agent. S. lappa showed analgesic activity in all test systems in a dose- and time-dependent manner. In addition, the formulated cream obtained from the essential oil showed very promising pharmaceutical and pharmacological properties. The analgesic activity of S. lappa may be due to its interaction with opioid receptors and involvement of peripheral analgesia. The ability of S. lappa to show both slow- and fast-onset analgesic effects suggests it could be used as a drug candidate for pain management. The current findings thus warrant further research in the development of this novel analgesic agent.

Interaction of auditory and pain pathways: Effects of stimulus intensity, hearing loss and opioid signaling

Moderate intensity sounds can reduce pain sensitivity (i.e., audio-analgesia) whereas intense sounds can induce aural pain, evidence of multisensory interaction between auditory and pain pathways. To explore auditory-pain pathway interactions, we used the tail-flick (TF) test to assess thermal tail-pain sensitivity by measuring the latency of a rat to remove its tail from 52 °C water. In Experiment 1, TF latencies were measured in ambient noise and broadband noise (BBN) presented from 80 to 120 dB SPL. TF latencies gradually increased from ambient to 90 dB SPL (audio-analgesia), but then declined. At 120 dB, TF latencies were significantly shorter than normal, evidence for audio-hyperalgesia near the aural threshold for pain. In Experiment II, the opioid pain pathway was modified by treating rats with a high dose of fentanyl known to induce post-treatment hyperalgesia. TF latencies in ambient noise were normal 10-days post-fentanyl. However, TF latencies became shorter than normal from 90 to 110 dB indicating that fentanyl pre-treatment had converted audio-analgesia to audio-hyperalgesia. In Experiment III, we tested the hypothesis that hearing loss could alter pain sensitivity by unilaterally exposing rats to an intense noise that induced a significant hearing loss. TF latencies in ambient noise gradually declined from 1- to 4-weeks post-exposure indicating that noise-induced hearing loss had increased pain sensitivity. Our results suggest that auditory and pain pathways interact in ways that depend on intensity, hearing loss and opioid pain signaling, results potentially relevant to pain hyperacusis.

561-P: Activated Xanthine Oxidase in Serum Is a Potent Therapeutic Target for Experimental Diabetic Polyneuropathy

Xanthine oxidase (XO), a potent inducer of reactive oxygen species, catalyzes purine metabolism. XO is expected to be implication of the macrophage activation. XO is also expressed in the peripheral nerve system, while its role in diabetic polyneuropathy (DPN) has not been clarified. We explored the implication of XO in DPN of db/db mice (db/db) treating with XO-inhibitor, topiloxostat (To). C57BL6 mice (C57) and db/db (5 wks of age) were daily treated with 1mg/kg (dbT1) and 2mg/kg (dbT2) To (per os) for 8 wks. During experimental period, peripheral nerve function was monitored. At end, serum and dissected sciatic nerves and dorsal root ganglia (DRG) served for evaluation of uric acid metabolism. Primary culture of DRG neuron was performed to evaluate the effects of To on neurite outgrowth in vitro. To improved significant delay of nerve conduction velocities and elevation of threshold for tail flick test in db/db in a dose dependent manner (p&amp;lt;0.05 dbT2 vs. C57 for NCVs, p&amp;lt;0.05 db/db vs. dbT1, p&amp;lt;0.01 db/db vs. dbT2 for tail flick). XO activity was significantly up-regulated in DRG (p&amp;lt;0.01) and serum of db/db compared to those of W (p&amp;lt;0.05). To successfully suppressed the elevated XO activity in a dose dependent manner (p&amp;lt;0.05, W vs. T1, p&amp;lt;0.01, T1 vs. T2). Uric acid was significantly accumulated in serum and DRG of db/db compared to those of C57 (p&amp;lt;0.05). To could significantly reduce the accumulation (p&amp;lt;0.01). In primary culture of DRG neuron, extrinsic 100 μM XO depleted the neurite outgrowth more than 50 % than that of non-stimulated neurons (p&amp;lt;0.01). 4.3ng/ml To could significantly restored the reduction of neurite outgrowth compared to that of non-treated neurons (p&amp;lt;0.05). As a conclusion, increase in XO activity in serum and DRG may be implicated in the pathophysiology of DPN in db/db. Activation of XO in serum may directly exacerbate neuronal injury for DRG in DPN. To has a beneficial effect on DPN through its specific property to suppress serum XO activity. Disclosure H. Ichinohe: None. H. Mizukami: None. S. Osonoi: None. K. Kudo: None. S. Yagihashi: None.

Pharmacological approach to mechanism of action of tramadol in murine nociception and inflammation assays

The analgesic activity of tramadol has been recognized both in man and in several animal models of pain. However an extensive characterization of the opioid mechanism of action of tramadol of pain has not been reported. The objective of the present study was to evaluate the antinociceptive and anti-inflammatory activity of tramadol in different animal pain models and to determine the effect of the selective opioid antagonist: naltrexone, naltrindole and nor-binaltorphimine. The i.p. administration of tramadol induced a dose-dependent with the following order of potency: formalin hind paw, phase II > formalin hind paw, phase I> acetic acid writhing > tail flick > hot plate. Pretreatment of the mice with naltrexone (1 mg/kg i.p.) antagonized tramadol activity in the acetic acid writhing test, in the hot plate and the tail flick assays, however lack of effect in the formalin hind paw assays. Naltrindole (1 mg/kg i.p.) did not induce a significant change in all the murine assays. However, the mice pretreated with nor-binaltorphimine (1 mg/kg, i.p.) did not modified the tramadol antinociception in the acetic acid writhing and in the hot plate assays. Besides, nor-binaltorphimine pretreatment reversed significantly the tramadol effect in the tail flick and in the formalin hind paw assays. This findings suggests that tramadol effect is mediated by MOR and KOR rather DOR receptors.

Effects of lincomycin hydrochloride on the neurotoxicity of zebrafish.

Lincomycin hydrochloride is one of the commonly used drugs in clinic. However, it has many side effects on patients, and its mechanism is still poorly understood. In this study, 6h post-fertilization (6 hpf) zebrafish embryos were exposed to several concentrations of lincomycin hydrochloride (15, 30, 60μg/mL) for up to 24 or 96 hpf to detect their developmental toxicity and neurotoxicity, and to 6 days post-fertilization (6 dpf) to detect their behavioral toxicity. Our results showed that lincomycin hydrochloride could lead to embryonic head deformities (unclear ventricles, smaller ventricles, fewer new neurons). The studies showed that the frequency of spontaneous tail flick of zebrafish embryo increased at 24 hpf, and the lincomycin hydrochloride exposed zebrafish embryos showed increased heart rate, shorter body length, and yolk sac edema with severe pericardial edema at 96 hpf. The studies also showed that lincomycin hydrochloride increased oxidative stress level, Acetylcholinesterase (AChE) activity, ATPase activity and apoptosis in zebrafish larvae. In addition, the swimming behavior of zebrafish larvae decreased with the increase of lincomycin hydrochloride concentration, but the angular velocity and meandering degree increased, which might be due to the decreased activity of AChE and ATPase, as well as the decreased expression of genes related to neurodevelopment and neurotransmitter system, leading to the change of their motor behaviors. In summary, we found that lincomycin hydrochloride induced developmental toxicity and neurotoxicity in zebrafish larvae, contributing to a more comprehensive evaluation of the safety of the drug.

The functions of tail flicking in birds: A meta-analysis

Tail flicking is a common behavior that can be observed in many bird species. Various studies have investigated this behavior in different contexts such as during foraging, social interactions, or during predator–prey interactions. Nonetheless, there has been no statistical synthesis of results concerning the most commonly hypothesized functions of tail flicking. We conducted meta-analyses of published studies reporting flicking rates of birds in different contexts to identify a general function of tail flicking across species. We found evidence that tail flicking does not serve only one function but most likely has various functions across species. We found the general trend for flicking being a reflection of vigilance and predation risk. Flicking was related to flock size as rates decreased with increasing flock size, which might be related to a decreased individual predation risk in larger flocks. Moreover, we found flicking to be related to body condition and prey flushing. However, effect sizes for these hypotheses were only available from very few studies (body condition k = 2, prey flushing k = 3). Hence, future research concerning these two functions are necessary. Finally, our results suggested that flicking is not used for social communication, as it was not related to the presence of a conspecific or social status of an individual.

Insect-repelling behavior in goitered gazelles: responses to biting fly attack

Ungulates suffer greatly from a variety of biting flies, the results of which decrease their feeding and resting time and force them to move to lower-quality habitats and unvegetated areas. This in turn leads to weight loss in adults, lower milk production in mothers, and growth retardation in young. An ungulate’s first line of defense against blood-sucking flies is its insect-repelling behaviors that include head waving, ear flapping, tail flicking, and foot stamping. Ungulates also can respond to a biting fly attack by gathering into larger groups to lessen the number of flies per individual (dilution effect) and by finding microhabitats with lower temperatures and stronger winds, where fewer biting flies are found. In this paper, I considered the insect-repelling behaviors of goitered gazelles to better understand the protection strategies of wild ungulates against fly attacks to enhance the management of domestic animals. I found that (a) goitered gazelles demonstrated the highest rate of insect-repelling behavior during the hot and windless summer months, which was the most favorable time of year for biting fly activity; (b) smaller body-sized fawns and sub-adults performed fly defensive behaviors significantly less often than adults, while there were no differences in repelling behavior rates between adult males and females in spite of the discrepancy in their body sizes; (c) goitered gazelles increased their group sizes through the summer months of high biting fly activity; and (d) during summer, the gazelles used landscape features to find elevated and unvegetated sites with lower temperatures and higher wind speeds to lower fly activity. Blood-sucking fly activity is very likely a powerful environmental factor under which ungulate hosts significantly modify their behaviors in order to escape the pain and harassment—and lessen the costs—from biting fly attacks.

Glabridin Alleviates Inflammation and Nociception in Rodents by Activating BK&lt;sub&gt;Ca&lt;/sub&gt; Channels and Reducing NO Levels

Inflammation, and the pain that accompanies it, is a natural response of the body. The licorice plant (Glycyrrhiza glabra) have demonstrated anti-inflammatory, anti-edematous, and anti-nociceptive effects of its extracts. The effective ingredient remains unidentified; however, one possibility is the unique isoflavone glabridin. The anti-nociceptive, and anti-inflammatory effects of glabridin and its possible mechanism with focus on the large conductance Ca2+-activated K+ (BKCa) channels and L-arginine-nitric oxide (NO) pathway were examined by using different tests. In order to determine the anti-edematous, anti-nociceptive, and anti-oxidative effects of glabradin, some tests such as the tail flick, hotplate, carrageenan-induced paw edema, air pouch, acetic-acid-induced writhing, formalin, and capsaicin tests, as well as toxicity and open field tests were made. Glabridin was administered to rats (n = 8) or mice (n = 8) for 3 d at 3 doses (10, 20, and 40 mg/kg). Glabridin inhibited cytokine production and showed an anti-nociceptive response via the activating of BKCa channels and downregulating NO level and partially transient receptor potential vanilloid-1 pathways. It also demonstrated anti-inflammatory effects by inhibiting cyclooxygenase (COX) activity, while showing no cytotoxicity. Glabridin, however, showed no anti-nociceptive effect in the neurogenic phase. Glabridin is a promising substance in terms of its anti-nociceptive and anti-inflammatory effects by disrupting peripheral NO production, inhibiting cyclic guanosine monophosphate (cGMP) activation and activating BKCa channels and its lack of acute and subacute toxic effects.

Clinico-physiological and haemato-biochemical evaluation of midazolam-ketofol anaesthesia in atropinized goats

The study was conducted on six healthy non-descript goats of either sex weighing between 20-25 kg by administrating atropine sulphate (0.04 mg/kg I/M) followed by midazolam (0.4 mg/kg I/M) and 15 min. later followed by induction of anaesthesia with ketofol (5mg/kg I/V). Sedation with drooping of head after midazolam administration within 8.20±0.58 min. After ketofol administration went into lateral recumbency and onset of anaesthesia was 0.62±0.14 min. Corneal, palpebral and anal pinch reflexes were abolished completely. Complete relaxation of all muscles of jaw, tail, anus, prepuce, neck and limb was observed but for short duration. There was complete analgesia and moderated salivation after ketofol anaesthesia. The average duration of anaesthesia was 33.71±1.08 min. after which sign of recovery such as raising of head, tail flicking appeared and complete recovery took 62.14±1.53 min. after ketofol anaesthesia. There was no significant variations in rectal temperature whereas a significant (P

Emergency obstacle avoidance trajectory tracking control based on active disturbance rejection for autonomous vehicles

To solve the problem of understeer and oversteer for autonomous vehicle under high-speed emergency obstacle avoidance conditions, considering the effect of steering angular frequency and vehicle speed on yaw rate for four-wheel steering vehicles in the frequency domain, a feed-forward controller for four-wheel steering autonomous vehicles that tracks the desired yaw rate is proposed. Furthermore, the steering sensitivity coefficient of the vehicle is compensated linearly with the change in the steering angular frequency and vehicle speed. In addition, to minimize the tracking errors caused by vehicle nonlinearity and external disturbances, an active disturbance rejection control feedback controller that tracks the desired lateral displacement and desired yaw angle is designed. Finally, CarSim® obstacle avoidance simulation results show that an autonomous vehicle with the four-wheel steering path tracking controller consisting of feed-forward control and feedback control could not only improve the tire lateral forces but also reduce tail flicking (oversteer) and pushing ahead (understeer) under high-speed emergency obstacle avoidance conditions.

Phytochemical Investigation, Acute Toxicity, Central Analgesic and Antioxidant Activities of Extracts and Essential Oil of Cotula cinerea Del (Asteraceae)

Background:Cotula cinerea belongs to the Asteraceae family and grows in desert areas such as Moroccan Sahara. The use of this plant in Moroccan traditional medicine prompted us to investigate its chemical composition, its acute oral toxicity, its analgesic and antioxidative activities.Methods:Extraction was conducted by steam distillation for essential oil and by maceration using solvents (hexane, ethyl acetate, n-butanol) for other non-volatile compounds. Quantitative analysis of total polyphenols, procyanidins and flavonoids was conducted through spectrophotometric assays. Qualitative phytochemical composition of the essential oil was investigated by GC/MS analysis. Acute oral toxicity was tested at a dose of 2000 mg/kg in mice. Central analgesic effect was assessed in rat using tail flick and hot plate models and the obtained results were compared to morphine. Antioxidant activity of the essential oil and the obtained extracts was evaluated through 2,2-diphenyl-1- picrylhydrazyl (DPPH°) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and the obtained results were compared to TROLOX.Results:The obtained results showed that the studied extracts contained significant amounts of total polyphenols, flavonoids and condensed tannins. The phytochemical composition of the essential oil was predominated by thujone, eucalyptol and santolinatriene. The results of the acute oral toxicity showed that the tested essential oil and extracts were not toxic even at the highest dose of 2000 mg/kg. Experiments on analgesic activity showed that the administered extracts have a central analgesic effect. The highest effect was observed with the n-butanol and ethyl acetate extracts for both tail-flick and hot plate tests. The antioxidant activity of the explored extracts showed higher scavenging activities of the studied samples compared to TROLOX.Conclusion:Our results indicate thus that C. cinerea could be considered as a source of various secondary metabolites including terpenoids and polyphenols. Exploration of its biological activities showed that the plant essential oil and extracts possessed antioxidant and analgesic effects. Based on the results of this study, it is likely that extracts of C. cinerea could open perspectives for its use for pain relief.

Quercetin prevents alterations of behavioral parameters, delta-aminolevulinic dehydratase activity, and oxidative damage in brain of rats in a prenatal model of autism.

Autism is a neuropathology characterized by behavioral disorders. Considering that oxidative stress is involved in the pathophysiology of this disease, we evaluated the effects of quercetin, a flavonoid with antioxidant and neuroprotective properties, in an experimental model of autism induced by valproic acid (VPA). Twelve pregnant female rats were divided into four groups (control, quercetin, VPA, and VPA+quercetin). Quercetin (50mg/kg) was administered orally to the animals from gestational days 6.5 to 18.5, and VPA (800mg/kg) was administered orally in a single dosage on gestational day 12.5. Behavioral tests such as open field, social interaction, and tail flick nociceptive assays were performed on pups between 30 and 40days old, after which the animals were euthanized. Cerebral cortex, hippocampus, striatum, and cerebellum were collected for evaluation of oxidative stress parameters. The pups exposed to VPA during the gestational period showed reduced weight gain, increased latency in the open field and tail flick tests, reduced time of social interaction, accompanied by changes in oxidative stress parameters mainly in the hippocampus and striatum. Prenatal treatment with quercetin prevented the behavioral changes and damage caused by oxidative stress, possibly due to its antioxidant action. Our findings demonstrated that quercetin has neuroprotective effects in an animal model of autism, suggesting that this natural molecule could be an important therapeutic agent for treatment of autism spectrum disorders (ASDs).