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BACKGROUND: It has been considered that Cestrum nocturnum L. (CNL) has the effects of antiarrhythmia, local anesthesia and central inhibition.OBJECTIVE: To investigate the analgesic effect of CNL extract on mice,so as to find new drugs for clinical treatment of pain.DESIGN: A randomized control observation.SETTING: Center of Modern Education and Department of Pharmacology,Gannan Medical College.MATERIALS: The experiments were carried out in the laboratory of scientific research center, Gannan Medical College between March and April in 2005. ① A total of 150 healthy adult Kunming mice were used in four independent experiments. ② Drugs: CNL extract was provided by the Department of Phytochemistry, Shenyang Pharmaceutical University (batch number: 2002080901), morphine hydrochloride injection by Shenyang No.1Pharmaceutical Factory (batch number: 000305), and naloxone hydrochloride injection by Yanqiao (Hunan) Pharmaceutical Co. Ltd., (batch number:20021109).METHODS: ① Effects of CNL extract on writhing times induced by acetic acid: Forty female mice were randomly divided into four groups with10 mice in each, and they were treated with intraperitoneal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 0.10 mg/g aminophenazone respectively. The intraperineal injection of 6 g/L glacial acetic acid was given after 15 minutes. The writhing times of mice within 15 minutes were observed and recorded in each group. ② Effects of CNL extract on the pain induced by hot pla in mice: Forty female mice were randomly divided into four groups with 10 mice in each, and they were treated with intraperineal injections of 0.02 mL/g saline, 0. 10 and 0.20 mg/g CNL extract and 0.10 mg/g morphine respectively. The pain responses were detected at 15, 30 and 60 minutes after administration. ③ The antagonistic effect of naloxone on morphine and CNL extract to the pain induced by hot plate in mice: Thirty female mice were randomly divided into three groups ith 10 mice in each group, and they were given intraperitoneal injections of 0.02 mL/g saline, naloxone 0.004 mg/g +morphine 0.01 mg/g and naloxone 0.004 mg/g+CNL extract 0.01 mg/g respectively. The pain responses were detected at 15, 30 and 60 minutes after administration respectively. ④ Effects of CNL extract on electrostimulation induced pain in mice: Forty mice were randomly divided into four groups with 10 mice in ach group, and they were administrated with intraperineal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 1 g/L morphine respectively. Repeated electrostimulations were given at 20, 35, 50 and 70minutes after administration, and the pain responses were detected by means of electrostimulation.MAIN OUTCOME MEASURES: ① Writhing times; ② Time for the pain response induced by hot plate; ③ Analgesic rate induced by electrostimulation.RESULTS: Totally 150 healthy adult Kunming mice were used in the four independent experiments, and all were involved in the analysis of results. ①Writhing times in the mice: 0.10 and 0.20 mg/g CNL extracts and 0.10 mg/g aminophenazone had very significant analgesic effects on writhing induced byacetic acid in mice, and the writhing times after administration were all fewer than those in the saline group (20.2±10.8, 14.5±7.6, 7.6±4.5,50.6±15.5, P ＜ 0.01), and the analgesic effects of CNL extract were dosedependently. ② Time for the pain response induced by hot plate: 0.10 and 0.20 mg/g CNL extracts had significant analgesic effects on the pain in duced by hot plate, and the time for pain sensation at 15, 30 and 60 minutes after administration were all longer than those in the saline group (P ＜ 0.05 or P ＜ 0.01), and the analgesic effect was dose-dependently. The times for pain sensation at each time point after administration in the naloxone 0.004 mg/g+CNL extract 0.01 mg/g group were all longer than those in the saline group, but those were close between the naloxone 0.004 mg/g+morphine 0.01 mg/g group and the saline group. ③ Analgesic rate induced by electrostimulation in the mice: The analgesic rates at20, 35, 50 and 70minutes after administration in the CNL extract 0.10 and 0.20 mg/g groups were all higher than those in the saline group (P ＜ 0.01).CONCLUSION: Our data suggested that CNL extract has obvious analgesic effect, and the analgesic intensity is dose-dependently. Naloxone, an opiate receptor antagonist, can antagonize the analgesic effect of morphine,but cannot antagonize that of CNL extract on mice with pain induced by hot plate, which indicates that CNL extract exert its analgesic role not through binding with opiate receptor.
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BACKGROUND: The water extract of white mulberry root-bark plays certain roles in decreasing the blood glucose and blood lipids of rats, antagonizing inflammation and analgesia, relieving asthma and inducing diuresis,as well as relaxing the smooth muscle.OBJECTIVE: To analyze the hypoxic tolerance of white mulberry rootbark by using the hypoxic tolerance test under normal pressure, rapid head-cut test and the test of isoproterenol in enhancing myocardial oxygen consumption.DESIGN: A randomized control study.SETTING: Department of Pathology and Department of Pharmacology,School of Basic Medical Sciences, Gannan Medical College.MATERIALS: The experiments were conducted in the laboratory of the Scientific Research Center of Gannan Medical College between May and June in 2003. Totally 106 healthy adult Kunming mice were used in the following three independent experiments. The white mulberry root-bark extract was provided by the Department of Pharmacology of Gannan Medical College, injection of propranolole hydrochloride by Beijing Pharmaceutical Factory.METHODS: ① Hypoxic tolerance test under normal pressure: Forty mice were divided into four groups with 10 mice in each group according to the method of random number table: saline group, propranolol group, white mulberry root-bark extract groups treated with 0.10 and 0.20 mL/g respectively, and the mice were treated with intraperitoneal injection of saline (0.02 mg/g), propranolol (10 g/L), white mulberry root-bark extract (0.10 and 0.20 mL/g) respectively. After 15 minutes,the mice in the groups were placed into the enclosed 250mL ground and wide mouthed bottles separately, and the survival time of the mice was observed by taking the last breath as the index. ② Rapid headcut test: Thirty mice were divided into three groups with 10 mice in each group according to the method of random number table: saline group, white mulberry root-bark extract groups treated with 0.10 and 0.20 mL/g respectively, and the mice were treated with intraperitoneal injection of saline (0.02 mg/g), white mulberry root-bark extract (0.10and 0.20 mL/g) respectively. After 15 minutes, the heads of the mice were rapidly cut down without anesthesia, and the time from cutting head to the last breath was recorded. ③ Test of isoproterenol in enhancing myocardial oxygen consumption: Thirty-six mice were divided into three groups with 12 mice in each group according to the method of random number table: saline group, isoproterenol group and white mulberry root-bark extract group treated with 0.10 mL/g. In the saline group, the mice were injected with saline subcutaneously (0.03 mL/g),and then intraperitoneally (0.02 mL/g) after 5 minutes. In the isoproterenol group, the mice were firstly treated with subcutaneous injection of isoproterenol (0.015 mg/g), and the intraperitoneal injection of saline (0.02 mL/g) was given after 5 minutes. In the white mulberry root-bark extract group treated with 0.10 mL/g, the mice were firstly injected subcutaneously with isoproterenol (0.015 mg/g), and then injected intraperitoneally with white mulberry root-bark extract (0.01 mL/g)was given after 5 minutes. After 15 minutes, the mice were placed into the enclosed wide mouthed bottles separately, and the survival time of the mice was observed.MAIN OUTCOME MEASURES: The survival time of mice in each group was observed in the three independent experiments.RESULTS: All the 106 healthy adult Kunming mice were involved in the analysis of results. ① Effect of white mulberry root-bark extract on the survival time of mice in the condition of hypoxic tolerance under normal pressure: As compared with the saline group, the survival times in the propranolol group and white mulberry root-bark extract groups treated with0.10 and 0.20 mL/g were obviously prolonged [(36.2±4.3), (81.0±17.0), (66.4±8.9), (90.3±7.4) minutes, t=3.358-3.617,P ＜ 0.01]. ② Effect of white mulberry root-bark extract on the survival time of mice under the condition of cerebral ischemia: As compared with the saline group, the times from cutting head to the last breath in the white mulberry root-bark extract groups treated with 0.10 and 0.20 mL/g were obviously prolonged [(17.8±1.3), (21.2±0.8), (23.5±0.7) minutes, t=2.824-3.432, P ＜ 0.05 or 0.01]. ③ Effect of white mulberry root-bark extract on the survival time of mice under the condition of myocardial oxygen consumption enhanced by isoproterenol: As compared with the saline group, the survival time in the isoproterenol group was obviously shortened, but those in the white mulberry rootbark extract groups treated with 0.10 and 0.20 mL/g were markedly prolonged [(36.2±4.3), (27.9±2.6), (50.6±3.4) minutes, t=2.734-3.035, P ＜ 0.05].CONCLUSION: White mulberry root-bark extract has obvious effect on hypoxic tolerance.
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BACKGROUND: Bistort rhizome is also named as caoheche, which is characterized by clearing heat, relieving convulsion, regulating damp and reducing swelling. Additionally, its water extract is characterized by antiarrhythmia and central inhibition; however, analgesia should be studied further.OBJECTIVE: To observe analgesic effect of polygonum bistorta L. Water extract, and compare with morphine and amidazofen.DESIGN: Completely randomized digital table and randomized controlled animal study.SETTING: Department of Pharmacology, Gannan Medical College.MATERIALS: The experiment was carried out in the Laboratory of Scientific Center of Gannan Medical College from March to May 2004. ① A total of 150 healthy adult Kunming mice were used in the 4 independent experiments. ② Medicines: Polygonum bistorta L. Water extract (Department of Phytochemistry, Shenyang Pharmaceutical University; batch number: 2003061001); morphine hydrochloride solution (Shenyang First Pharmaceutical Factory; batch number: 000305); naloxone hydrochloride solution (Yanqiao pharmaceutical Co. Ltd.; batch number: 20021109).METHODS: ① Effect of polygonum bistorta L. Water extract on twisting-body reaction of mice induced by acetic acid: Forty mice were randomly divided into 4 groups: saline group, 0.10 and 0.15 mg/g polygonum bistorta L. Water extract groups and amidazofen group with 10 in each group. All mice were intraperitoneally injected with 0.02 mL/g saline,0.10 and 0.15 mg/g polygonum bistorta L. Water extract solution and 0.10 mg/g amidazofen, respectively. Fifteen minutes later, mice were intraperitoneally injected with 6 g/L 0.01 mL/g acetic acid glacial to record times of twisting-body reaction within 15 minutes. ② Effect of polygonum bistorta L. Water extract on pain response of mice induced by hot-plate test: Forty female mice were randomly divided into 4 groups:saline group, 0.10 and 0.15 polygonum bistorta L. Water extract groups and morphine group with 10 in each group. All mice were intraperitoneally injected with 0.02 mL/g saline, 0.10 and 0.15 mg/g polygonum bistorta L. Water extract solution and 0.01 mg/g morphine solution, respectively. GJ-8402 hot-plate pain response threshold detector was used in this study; pain response temperature was (55.0±0.5) ℃; pain response after licking hindfoot was regarded as reactive marker; latency of pain response threshold was within 60 s. Pain response was measured at 15, 30 and 60 minutes after administration with hot-plate test. ③ Effect of morphine, naloxone and polygonum bistorta L. Water extract on pain response of mice induced by hot-plate test: Thirty female mice were randomly divided into 3 groups: saline group, naloxone+morphine group and naloxone+polygonum bistorta L. Water extract group with 10 in each group. All mice were intraperitoneally injected with 0.02 mL/g saline, 0.004 mg/g naloxone solution+0.01 mg/g morphine solution and 0.004 mg/g naloxone solution+0.15 mg/g polygonum bistorta L. Water extract solution, respectivelu. Pain response was measured at 15, 30 and 60 minutes after administration with hot-plate test. ④ Effect of polygonum bistorta L. Water extract on pain response of mice induced by electric stimulation: Forty mice were randomly divided into 4 groups with 10 in each group. All mice were intraperitoneally injected with 0.02 mL/g saline, 0.10 and 0.15 mg/g polygonum bistorta L. Water extract and 1 g/L morphine, respectively. Pain response was measured at 20, 35, 50 and 70 minutes after administration with electric stimulus method.MAIN OUTCOME MEASURES: ① Times of twisting-body reaction; ②duration of pain response induced by hot-plate test; ③ analgesic rate induced by electric stimulation.RESULTS: All 150 healthy adult Kunming mice were involved in the final analysis. ① Times of twisting-body reaction: At 15 inutes after administration, times of twisting-body reaction were less in 0.10 and 0.15 mg/g polygonum bistorta L. Water extract group and amidazofen group than those in saline group [(15.1±11.1), (8.0±6.5), (6.3±3.2), (54.1±20.2) times, t=3.532-3.681, P ＜ 0.01]. ② Duration of pain response induced by hot-plate test:At 15, 30 and 60 minutes after administration, durations of pain response induced by hot-plate test were longer in 0.10 and 0.15 mg/g polygonum bistorta L. Water extract group and morphine group than those in saline group (t=2.676-3.683, P ＜ 0.05-0.01). ③ Duration of pain response was longer in naloxone + polygonum bistorta L. Water extract group than that in saline group at each time point after administration (t=2.676-3.563, P＜ 0.05-0.01); however, duration in naloxone + morphine group was close to that in saline group (P ＞ 0.05). ④ Analgesic rate induced by electric stimulation: At 20, 35, 50 and 70 minutes after administration, analgesic rate induced by electric stimulation was higher in 0.10 and 0.15 mg/g polygonum bistorta L. Water extract group and morphine group than that in saline group (t=3.455-3.634, P ＜ 0.01).CONCLUSION: ① Polygonum bistorta L. Water extract has the obviously analgesic effect, whose intensity is close to that of amidazofen and morphine. ② Naloxone, an opiate receptor antagonist, can resist analgesic effect of morphine but not that of polygonum bistorta L. Water extract. This suggests that analgesic effect of polygonum bistorta L. Water extract dose not react through exciting opiate receptor.
ABSTRACT
Aim To investigate the inhibitory effects of xanthotoxol(XT) on neutrophil infiltration and brain edema induced by focal cerebral ischemia-reperfusion injury in rats.Methods Focal cerebral ischemia-reperfusion model in rat was induced by transient occlusion of the middle cerebral artery for 2 hours and followed by 24 hours of reperfusion.XT(2.5,5 and 10 mg?kg-1,ip)was administered at 1 hour and 12 hours after the onset of ischemia,respectively.After 24 hours of reperfusion,the influence of XT on neurological deficit score,brain edema and infarct size were evaluated;the activity of Na+,K+-ATPase,Ca2+-ATPase and myeloperoxidasse(MPO) in the ischemic hemisphere cortex of the middle cerebral artery area was assayed by spectrophotometry;the expression of intercellular adhesion molecule-1(ICAM-1) and E-selectin was measured with immunohistochemistry.Results XT significantly reduced the neurological deficit score,brain edema and infarct size,enhanced activity of Na+,K+-ATPase and Ca2+-ATPas,suppressed the injury-induced upregulation of MPO activity and cell adhesion molecules(ICAM-1 and E-selectin) expression in the brain tissue.Conclusion XT attenuates brain damage following focal cerebral ischemia-reperfusion in rats and its mechanism may partly be due to the inhibition of inflammation and brain edema induced by ischemia-reperfusion.