Nurcan Bektas

Antinociceptive activity of methanol extract of fruits of Capparis ovata in mice.

ETHNOPHARMACOLOGICAL RELEVANCE Capparis ovata Desf. and Capparis spinosa L. have wide natural distribution in Turkey and they are consumed in pickled form. Flower buds, root bark, and fruits of the plant are used in folk medicine due to their analgesic, wound healing, cell regeneration, tonic, and diuretic effects. AIM OF THE STUDY In this study, we attempted to identify the possible antinociceptive action of methanol extract prepared from fruits of Capparis ovata. MATERIALS AND METHODS Using tail immersion, hot plate and writhing tests, the antinociceptive effect of the methanol extract of Capparis ovata (MEC) fruits was assessed after intraperitoneal administration into mice. Morphine sulfate (5mg/kg; i.p.) and diclofenac (10mg/kg; i.p.) were used as reference analgesic agents. Naloxone (5mg/kg; i.p.) was also tested. RESULTS MEC was studied at the doses of 50, 100, and 200mg/kg (i.p.) and exhibited significant antinociceptive activities in all tests used. The above-mentioned doses of the extract reduced the writhing responses by 32.21, 55.70, and 68.36%, respectively. MPE% were increased by 7.27, 12.07, 14.60% in the tail immersion, and 7.88, 11.71, 16.73% in the hot plate test at the tested doses, respectively. Naloxone antagonized antinociceptive effect at the doses of 100 and 200mg/kg whereas partially antagonized the effect of MEC at the dose of 50mg/kg. CONCLUSIONS Based on the results obtained, it can be concluded that MEC has antinociceptive effects both at the peripheral and central levels.

Antithrombotic effects of ethanol extract of Crataegus orientalis in the carrageenan-induced mice tail thrombosis model.

INTRODUCTION Crataegus species (common name is Hawthorn) are medicinal plants, which have flavonoids, triterpene acids, proanthocyanidins, and organic acids as main constituents, used in the treatment of cardiovascular diseases. One of the main causes of multiple cardiovascular diseases is intravascular thrombosis and current agents, which are used for the treatment and prevention of thrombosis, have some side effects. Therefore, new antithrombotic and thrombolytic agents are still needed. MATERIALS AND METHODS Antithrombotic function of ethanol extract of Crataegus orientalis (COE) leaves was investigated in carrageenan-induced mice tail thrombosis model. Mice were injected with 40 μl (1%) carrageenan (Type I) dissolved in physiological saline by intraplantar administration in the right hind paw. After carrageenan injection, the extract was administered at the doses of 100, 200, and 300 mg/kg. Heparin was used as a positive control (10 and 100 IU). The length of tail-thrombosis was measured at 24th, 48th, and 72nd hours. RESULTS AND CONCLUSION 100mg/kg COE and 10IU heparin were not significant when compared to control groups at the time interval (24-72 h) that results was obtained. At 24th hour, both 200 and 300 mg/kg of COE showed a significant antithrombotic activity (p<0.05 and p<0.01, respectively). However, 200 mg/kg COE lost its significance and there was a decrease in the significance values of 300 mg/kg COE (p<0.05) at 48 and 72 h. From these results, it was concluded that COE significantly inhibited carrageenan-induced mice tail thrombosis in vivo.

Antinociceptive effect of methanol extract of Capparis ovata in mice.

Context: Capparis ovata Desf. (Capparaceae) grows widely in Turkey. Flower buds and fruits of the plant are used in folk medicine for their analgesic, antirheumatismal, and diuretic effects. Objective: This study evaluated the possible antinociceptive effect of the methanol extract of C. ovata (CME) in mice. Materials: The antinociceptive effect of methanol extract, prepared with the C. ovata flower buds, was studied at the doses of 50, 100, and 200 mg/kg (i.p.) using tail-immersion, hot-plate, and writhing tests in mice. Morphine sulfate (5 mg/kg; i.p.) and dipyrone (100 mg/kg; i.p.) were used as reference analgesic agents. Naloxone (5 mg/kg; i.p.) was also tested. Results: It was observed that the C. ovata extract had a significant antinociceptive effect in these tests. In the hot-plate and tail-immersion test results, the doses of 50, 100, and 200 mg/kg increased the percentage of the maximum possible effect (MPE%) value for nociception significantly according to the control value (P < 0.001). All doses of the extract decreased the number of acetic acid-induced abdominal constrictions in mice when compared with control group (P < 0.001). These effects were inhibited by pretreatment with naloxone. Discussion and conclusion: Based on the results obtained, it can be concluded that CME is a potentially antinociceptive agent which acts as both at the peripheral and central levels.

Investigation for anti-inflammatory and anti-thrombotic activities of methanol extract of Capparis ovata buds and fruits.

ETHNOPHARMACOLOGICAL RELEVANCE Capparis ovata Desf. has wide natural distribution in Turkey and it is consumed in pickled form. Flower buds, root bark, and fruits of the plant are used traditionally due to their analgesic, anti-inflammatory, wound healing, anti-rheumatismal, tonic, and diuretic effects. AIM OF THE STUDY The aim of this study was to investigate the possible anti-inflammatory and anti-thrombotic effects of methanol extracts prepared from flower buds (CBE) and fruits (CFE) of C. ovata. MATERIALS AND METHODS Anti-inflammatory effects of CBE and CFE were assessed using carrageenan-induced and prostaglandin E₂-induced mouse paw edema models. For the anti-thrombotic effect evaluation, carrageenan-induced tail thrombosis model was performed in mice. The extracts were administered intraperitonally (i.p.) at the doses of 100, 200, and 300 mg/kg. The anti-inflammatory effect of Capparis extracts were tested in comparison to 10 mg/kg diclofenac and anti-thrombotic activity to 10 and 100 IU heparin. RESULTS CBE at the doses of 200, and 300 mg/kg and CFE at the doses of 100, 200, and 300 mg/kg showed significant anti-inflammatory activity and CFE reached therapeutic concentration early than CBE in carrageenan inflammation model. In prostaglandin E₂ inflammation model, CBE and CFE exhibited significant inhibitory effects. The C. ovata extracts did not show remarkable anti-thrombotic effect. CONCLUSIONS Based on the results obtained, it can be concluded that fruits of C. ovata have more potent anti-inflammatory effect than flower buds. It has been suggested that inhibition of cyclooxygenase pathway is one of the mechanisms of the activity. C. ovata may be potentially used as therapeutic agents for inflammatory diseases.

Evaluation of the antithrombotic effects of Crataegus monogyna and Crataegus davisii in the carrageenan-induced tail thrombosis model

Abstract Context: Crataegus species are widely used as herbal medicines for preventing cardiovascular diseases (CVDs). However, there are no studies on the effects of Crataegus monogyna Jacq. (Rosaceae) and C. davisii Browicz on thrombosis, which is an important mechanism in CVDs. Objective: The purpose of this study was to investigate the antithrombotic effects of ethanol extracts of Crataegus monogyna (CMEx) and C. davisii (CDEx) leaves by using the carrageenan-induced tail thrombosis model. Materials and methods: The hind paw of each mouse was injected with 1% Type I carrageenan to induce thrombosis. CMEx was tested at the doses of 100, 200, and 300 mg/kg and CDEx at the dose of 50, 100, 200, and 300 mg/kg in comparison with heparin. The lengths of tail thrombosis were measured at the 24, 48, and 72 h. Results: Does of 200 and 300 mg/kg CMEx showed significant effects (p < 0.01; p < 0.001) at 24 h when compared with the control group. The antithrombotic activity of 200 and 300 mg/kg CMEx showed a decrease at 48 and 72 h but the activity of 300 mg/kg dose of CMEx was still significant (p < 0.01). The activities of 50 and 100 mg/kg doses of CDEx were significant (p < 0.001; p < 0.01) between 24 and 72 h whereas 200 and 300 mg/kg CDEx did not show any significance. Discussion and conclusions: CMEx and CDEx significantly inhibited the carrageenan-induced mouse tail thrombosis. Based on these results, it was concluded that CDEx and CMEx may potentially be used as therapeutic agents or complementary treatments against thrombosis.

Effect of phenolic acids on functions of rat aorta, vas deferens and on metabolic changes in streptozotocin-induced diabetes.

Objectives: This study aimed to investigate the effects of antioxidant treatment on streptozotocin (STZ)-induced diabetic metabolic and smooth muscle (SM) complications in rats. Materials and Methods: Threeweeks after STZ injection (i.v.), vehicle, p-OH benzoic (p-OHBA), protocatechic (PA) and gallic acids (GA) were separately administered (10 mg/kg each, i.p.) to the rats everyday for 3 weeks. Metabolic functions were observedregularly. The rats in all groups were sacrificed andaorta and Vas deferens were dissected. Theresponses of isolated organs to agonists (acetylcholine and phenylephrine) were recorded. Results: Protocatechic acid prevented increase in food consumption and feces output significantly. The responses of isolated organs to agonists increased in the STZ-diabetic rats. The test drugs either prevented, exacerbated or didnot affect the SMchanges in the STZ-diabetic rats. Conclusions: It was concluded that p-OHBA, PA and GA may cause effects independently of their antioxidant effect and/or of diabeticcomplications. They may exhibit pro-oxidant activities in the experimental conditions applied.

Valnoctamide: The effect on relieving of neuropathic pain and possible mechanisms

Abstract The purpose of this study is to assess the possible anti‐allodynic and antihyperalgesic effect of valnoctamide, an amide derivative of valproic acid, at the doses of 40, 70 and 100 mg/kg (i.p.) in neuropathic pain model induced by chronic constriction injury in rats, by using dynamic plantar test and plantar test (Hargreaves method), and to evaluate that the possible role of certain serotonin, noradrenergic, opioid and GABAergic receptors by pre‐treatment with 1 mg/kg (i.p.) ketanserin, yohimbine, naloxone and 0.5 mg/kg (i.p.) bicuculline, respectively. 70 and 100 mg/kg valnoctamide significantly increased the mechanical and thermal thresholds decreasing with the development of neuropathy and demonstrated anti‐allodynic and antihyperalgesic activity. Limited contribution of serotonin 5‐HT2A/2C receptors and &agr;2‐adrenoceptors, and significant contribution of GABAA and opioid receptors to the anti‐allodynic activity have been identified whereas remarkable contribution of opioid receptors and significant contribution of serotonin 5‐HT2A/2C receptors, &agr;2‐adrenoceptors, GABAA receptors to the antihyperalgesic activity have been identified. Based upon these findings and considering that valnoctamide has safer side‐effect profile, it is possible to say that valnoctamide is a potential agent that might be used alone or in combination with the other effective therapies in the alleviating of neuropathic pain.

The imidazoline receptors and ligands in pain modulation

Pain is an unpleasant experience and effects daily routine negatively. Although there are various drugs, many of them are not entirely successful in relieving pain, since pain modulation is a complex process involving numerous mediators and receptors. Therefore, it is a rational approach to identify the factors involved in the complex process and develop new agents that act on these pain producing mechanisms. In this respect, the involvement of the imidazoline receptors in pain modulation has drawn attention in recent years. In this review, it is aimed to focus on the imidazoline receptors and their ligands which contribute to the pain modulation. It is demonstrated that imidazoline-2 (I2) receptors are steady new drug targets for analgesics. Even if the mechanism of I2 receptor is not well known in the modulation of pain, it is known that it plays a role in tonic and chronic pain but not in acute phasic pain. Moreover, the I2 receptor ligands increase the analgesic effects of opioids in both acute and chronic pain and prevent the development of opioid tolerance. So, they are valuable for the chronic pain treatment and also therapeutic coadjuvants in the management of chronic pain with opiate drugs due to the attenuation of opioid tolerance and addiction. Thus, the use of the ligands which bind to the imidazoline receptors is an effective strategy for relieving pain. This educational forum exhibits the role of imidazoline receptors and ligands in pain process by utilizing experimental studies.

The possible mechanisms of protocatechuic acid-induced central analgesia

It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300 mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300 mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT2A/2C receptor antagonist ketanserin (1 mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5 mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300 mg/kg in tail-immersion test, at the doses of 150 and 300 mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies.

Zonisamide: Antiproliferative and Antioxidant Effects on C6 Glioma Cancer Cell Model

Seizures are often seen in patients with brain tumors and antiepileptic drugs such as acetazolamide, valproic acid. Some of these antiepileptic drugs also have anti-cancer effects that have been shown in many studies. For instance, valproic acid has been shown to be related to apoptosis pathway and induced the suppression of C6 glioma cell migration. Zonisamide is also commonly used as an antiepileptic drug because of its scavenging effects on hydroxyl and nitric oxide radicals. Due to valproic acid’s anticancer activity, zonisamide was investigated for its antiproliferative and antioxidant effects on C6 glioma cells. The percentage of cell viability, measurement of DNA synthesis, superoxide dismutase activity and the measurement of glutathione were studied in the presence of zonisamide. IC50 value of zonisamide is 80 M at 48 hour. According to DNA synthesis (BrdU incorporation) analysis, IC50 value and lower concentration (50 M) of zonisamide reduced the rate of C6 glioma DNA synthesis significantly as compared to control cells. Zonisamide was also decreased SOD and GSH levels on glioma C6 cells depending on concentrations and incubation of time. Using of zonisamide with anti-cancer agents fighting against glioma cells might be useful because of its antiproliferative effects.