鸡屎藤（Paederia scandens）活性物质和镇痛药理活性研究
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摘要
鸡屎藤Paederia scandens (Lour.) Merri.是茜草科Rubiaceae鸡屎藤属Paederia的一种攀援性藤本植物,又名“鸡矢藤”,广泛分布于中国、日本、印度、菲律宾以及美国西海岸等国家。在东南亚一些国家,鸡屎藤作为民间传统草药和食物已有数千年的悠久历史。鸡屎藤的叶子在越南曾一度作为各种食物的调味品。
近年来,曾有许多报道,从植物鸡屎藤根、茎的甲醇提取物中陆续分离出鸡屎藤苷,车叶草苷,鸡屎藤苷酸,去乙酰车叶草苷,鸡屎藤次苷等环烯醚萜苷类和环烯醚萜苷二聚体类化合物。这些化学成分具有多种生物活性:如抗病毒、抗肿瘤、抗炎和抗微生物等。在中国、日本、越南和其他的一些东南亚国家,植物鸡屎藤的根、茎、藤皮、果实作为民间草药使用已有数千年的历史,尤其在治疗牙痛、胸痛、痔疮引发的疼痛,风湿性关节炎、脾脏炎症、杆菌性痢疾等方面具有显著的疗效。虽然植物鸡屎藤具有显著的镇痛疗效而在民间广为使用,但是目前关于该植物的镇痛药理活性物质基础以及镇痛作用机制的研究文献尚未报道。
基于以上调研,我们对植物鸡屎藤全株进行了甲醇提取,并对其醇提物应用石油醚、氯仿、正丁醇进行了分步骤萃取;同时首次应用镇痛药理方法学对其总提物以及各个萃取部位进行了镇痛药理活性研究。
植物鸡屎藤的甲醇提取物以口服的方式给受试小鼠给药,应用化学刺激和热刺激引发疼痛的动物模型对其镇痛药理活性进行研究。结果表明,口服给药剂量为600 mg/kg和900 mg/kg植物鸡屎藤甲醇提取物的受试小鼠在小鼠醋酸扭体实验、小鼠福尔马林实验和小鼠热水甩尾实验中对化学和热刺激引发的疼痛具有显著的耐受。另外,在小鼠福尔马林实验中植物鸡屎藤甲醇提取物表现出了中枢和外周双重镇痛机制。
应用化学刺激和热刺激引发小鼠疼痛的整体动物模型对植物鸡屎藤甲醇提取物正丁醇部位浸膏的镇痛药理活性进行研究。实验结果表明:口服给药剂量为150 mg/kg,300 mg/kg和600 mg/kg植物鸡屎藤甲醇提取物正丁醇部位浸膏的受试小鼠对腹腔注射醋酸溶液、足底皮下注射福尔马林溶液和辣椒素溶液引发的疼痛以及在小鼠热水甩尾实验和小鼠热板实验中对热刺激引发的疼痛均具有耐受性。其中剂量为600 mg/kg的正丁醇部位浸膏对化学和热刺激引发的疼痛具有极其显著的抑制作用。在小鼠戊巴比妥钠延长睡眠时间实验和小鼠开野实验中,正丁醇部位浸膏未能延长小鼠戊巴比妥钠引发的睡眠时间和影响受试小鼠的自主活动行为,这些结果表明正丁醇部位浸膏的镇痛活性与催眠作用和破坏脑部运动神经的毒性作用无关,具有特异性。另外,在小鼠福尔马林镇痛药理拮抗实验和小鼠辣椒素镇痛药理拮抗实验中,此镇痛药理活性对药理拮抗工具药纳络酮和格林本脲的拮抗作用不敏感,而完全被尼莫地平的拮抗作用拮抗;表明了正丁醇部位浸膏的镇痛药理活性与L-type Ca~(2+) channels有关。另外,从植物鸡屎藤正丁醇部位分离出多个环烯醚萜苷类和环烯醚萜苷二聚体类化合物,正丁醇部位的镇痛药理活性可能与这些化合物的协同作用有关;至于,在这些化合物中某个化合物是否具有强烈的镇痛药理活性还需进一步深入研究。
应用化学刺激和热刺激引发小鼠疼痛的整体动物模型对植物鸡屎藤甲醇提取物石油醚部位浸膏的镇痛药理活性进行研究。实验结果表明:口服给药剂量为20 mg/kg, 40 mg/kg和80 mg/kg植物鸡屎藤甲醇提取物石油醚部位浸膏的受试小鼠对腹腔注射醋酸溶液、足底皮下注射福尔马林溶液和辣椒素溶液引发的疼痛以及在小鼠热水甩尾实验和小鼠热板实验中对热刺激引发的疼痛均具有良好的耐受性。其中剂量为80 mg/kg的石油醚部位浸膏对化学和热刺激引发的疼痛具有极其显著的抑制作用。在小鼠戊巴比妥钠延长睡眠时间实验和小鼠开野实验中,石油醚部位浸膏未能延长小鼠戊巴比妥钠引发的睡眠时间和影响受试小鼠的自主活动行为,这些结果表明石油醚部位浸膏的镇痛活性与催眠作用和破坏脑部运动神经的毒性作用无关,具有特异性。另外,在小鼠福尔马林镇痛药理拮抗实验和小鼠辣椒素镇痛药理拮抗实验中,此镇痛药理活性对药理拮抗工具药纳络酮的拮抗作用不敏感,而完全被格林本脲的拮抗作用拮抗;表明了石油醚部位浸膏的镇痛药理活性与K~+-ATP channels有关。另外,通过应用GC-MS技术对石油醚部位化学成分进行分析发现其主要化合物为linoleic acid,the sterols和vitamin E。因此,我们推断石油醚部位镇痛药理活性与这些化合物的协同作用有关。
对从植物鸡屎藤醇提物正丁醇部位浸膏中分离出的环烯醚萜苷类和环烯醚萜苷二聚体类化合物,进行了镇痛药理动物模型筛选。结果发现,化合物鸡屎藤苷酸甲酯具有潜在的镇痛药理活性。应用化学刺激和热刺激引发小鼠疼痛的整体动物模型对该单体化合物的镇痛药理活性进行了深入研究。实验结果表明:腹腔注射给药剂量为20 mg/kg,40 mg/kg和60 mg/kg鸡屎藤苷酸甲酯的受试小鼠对腹腔注射醋酸溶液,足底皮下注射福尔马林溶液和辣椒素溶液引发的疼痛以及在小鼠热水甩尾实验和小鼠热板实验中对热刺激引发的疼痛均具有良好的耐受性。其中剂量为60 mg/kg的鸡屎藤苷酸甲酯对化学和热刺激引发的疼痛具有极其显著的抑制作用。在小鼠戊巴比妥钠延长睡眠时间实验和小鼠体内温度测定实验中,该化合物未能延长小鼠戊巴比妥钠引发的睡眠时间和影响受试小鼠的体温改变,这些结果表明鸡屎藤苷酸甲酯的镇痛活性与催眠作用和药物毒性作用无关,具有特异性。另外,在小鼠热板镇痛药理拮抗实验中,此镇痛药理活性对药理拮抗工具药纳络酮和尼莫地平的拮抗作用不敏感,而完全被亚甲基蓝、L-NAME、格林本脲的拮抗作用拮抗;表明了鸡屎藤苷酸甲酯的镇痛药理活性可能与NO-cGMP-K~+-ATP channels途径有关。
Paederia scandens (Lour.) Merri., a climbing plant, belonging to the family Rubiaceae, is popularly known as the name“Ji Shi Teng”in Chinese which is widely grown in China, Japan, India, Philippines and USA. It has been traditionally used as folklore medicine and food in Southeast of Asia for thousands of years. The leaves of the plant are used as an ingredient in various foods in Vietnam.
Recently, it has been reported that the iridoid glycosides and the dimeric iridoid glycosides- paederoside, asperuloside, paederosidic acid, deacetylasperuloside, scandoside were isolated from the MeOH extract from the stems and roots of P. scandens. These chemical constituents of P. scandens have biological activities such as anti-virus, anti-tumor, anti-inflammation and anti-microbial activities. In folklore medicine, the roots, leaves, barks and fruits of P. scandens have been used to treat toothache, chest pain, piles, inflammation of the spleen, diuretic, emetic, rheumatic arthritis and cure bacillary dysentery in China, Japan, Vietnam and other countries in the south-east Asia for thousands of years. Although P. scandens is a particularly useful pain- relief in folklore medicine, there has been no report on the anti-nociceptive activity of this plant and its mechanisms of analgesic activity so far.
Based on investigation above, we study the analgesic activity of the MeOH extracts of P. scandens and the anti-nociceptive activity of the petroleum ether, chloroform, n-butanol and water fractions from the MeOH extracts.
The MeOH extract from Paederia scandens was administered orally and studied on analgesic activity in chemical- and thermal- induced nociception models in mice. In acetic acid-induced writhing test, formalin test and tail-flick test, the significant inhibition of nociception was observed at the doses of 600 and 900 mg/kg. Moreover, the MeOH extract could relieve the central and peripheral nociception in the formalin test.
The n-butanol fraction of the MeOH extract from Paederia scandens was evaluated for antinociceptive activity in mice using chemical and thermal models of nociception. The n-butanol fraction, given orally at doses of 150, 300 and 600 mg/kg produced significant inhibition of chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections, and of thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at a dose of 600 mg/kg. In the pentobarbital sodium-induced sleeping time test and the open-field test, the n-butanol fraction neither significantly enhanced pentobarbital sodium-induced sleeping time nor impaired motor performance, indicating that the observed anti-nociception was unlikely to be due to sedation or motor abnormality. Moreover, the n-butanol fraction-induced anti-nociception in both the capsaicin and formalin tests was insensitive to naloxone or glibenclamide but was significantly antagonized by nimodipine. These results suggest that the n-butanol fraction produced anti-nociception possibly related to nimodipine-sensitive L-type Ca~(2+) channels, which merits further studies regarding the precise site and mechanism of action. Furthermore, iridoid glycosides isolated from the n-butanol fraction might be related to its antinociceptive action fraction. Therefore, the effect on analgesic activity of each chemical compound in large quantity might well be considered in a further study.
The petroleum ether fraction of MeOH extract from Paederia scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception. Given orally, the petroleum ether fraction (PEF) at doses of 20, 40 and 80 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 80 mg/kg of the petroleum ether fraction. In the pentobarbital sodium-induced sleeping time test and the open-field test, the petroleum ether fraction neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality. Moreover, the petroleum ether fraction-induced anti-nociception in both capsaicin and formalin tests was insensitive to naloxone, but was significantly antagonized by glibenclamide. These results suggested that the petroleum ether fraction produced anti-nociception possibly related to glibenclamide-sensitive K~+-ATP channels, which merited further studies regarding the precise site and mechanism of action. The major constituents of the petroleum ether fraction (PEF) determined by GC/MS analysis, are linoleic acid, the sterols and vitamin E. Therefore it can be suggested that they exert synergetic effects and are together responsible for the antinociceptive activity of the PEF-fraction.
We test the anti-nociceptive activity of iridoid glycosides isolated from the n-butanol fraction of the MeOH extract from Paederia scandens. Then we found the paederosidic acid methyl ester showed the potential anti-nociception. This iridoid glycoside was evaluated for anti-nociceptive activity in mice using chemical and thermal models of nociception. The paederosidic acid methyl ester, given intraperitoneal injection at doses of 20, 40 and 60 mg/kg, produced significant inhibition of chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections, and of thermal nociception both in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at a dose of 60 mg/kg. In the pentobarbital sodium-induced sleeping time test and the measurement of core body temperature, the chemical compound neither significantly enhanced pentobarbital sodium-induced sleeping time nor influent the temperature of core body, indicating that the observed anti-nociception was unlikely to be due to sedation or toxicity. Moreover, the paederosidic acid methyl ester -induced anti-nociception in the hot-pate test was insensitive to naloxone or nimodipine, but was significantly antagonized by methylene blue, L-NAME and glibenclamide. These results suggest that the paederosidic acid methyl ester produced anti-nociception possibly related to the anti-nociception pathway- NO-cGMP-K~+-ATP, which merits further studies regarding the precise site and mechanism of action.
近年来,曾有许多报道,从植物鸡屎藤根、茎的甲醇提取物中陆续分离出鸡屎藤苷,车叶草苷,鸡屎藤苷酸,去乙酰车叶草苷,鸡屎藤次苷等环烯醚萜苷类和环烯醚萜苷二聚体类化合物。这些化学成分具有多种生物活性:如抗病毒、抗肿瘤、抗炎和抗微生物等。在中国、日本、越南和其他的一些东南亚国家,植物鸡屎藤的根、茎、藤皮、果实作为民间草药使用已有数千年的历史,尤其在治疗牙痛、胸痛、痔疮引发的疼痛,风湿性关节炎、脾脏炎症、杆菌性痢疾等方面具有显著的疗效。虽然植物鸡屎藤具有显著的镇痛疗效而在民间广为使用,但是目前关于该植物的镇痛药理活性物质基础以及镇痛作用机制的研究文献尚未报道。
基于以上调研,我们对植物鸡屎藤全株进行了甲醇提取,并对其醇提物应用石油醚、氯仿、正丁醇进行了分步骤萃取;同时首次应用镇痛药理方法学对其总提物以及各个萃取部位进行了镇痛药理活性研究。
植物鸡屎藤的甲醇提取物以口服的方式给受试小鼠给药,应用化学刺激和热刺激引发疼痛的动物模型对其镇痛药理活性进行研究。结果表明,口服给药剂量为600 mg/kg和900 mg/kg植物鸡屎藤甲醇提取物的受试小鼠在小鼠醋酸扭体实验、小鼠福尔马林实验和小鼠热水甩尾实验中对化学和热刺激引发的疼痛具有显著的耐受。另外,在小鼠福尔马林实验中植物鸡屎藤甲醇提取物表现出了中枢和外周双重镇痛机制。
应用化学刺激和热刺激引发小鼠疼痛的整体动物模型对植物鸡屎藤甲醇提取物正丁醇部位浸膏的镇痛药理活性进行研究。实验结果表明:口服给药剂量为150 mg/kg,300 mg/kg和600 mg/kg植物鸡屎藤甲醇提取物正丁醇部位浸膏的受试小鼠对腹腔注射醋酸溶液、足底皮下注射福尔马林溶液和辣椒素溶液引发的疼痛以及在小鼠热水甩尾实验和小鼠热板实验中对热刺激引发的疼痛均具有耐受性。其中剂量为600 mg/kg的正丁醇部位浸膏对化学和热刺激引发的疼痛具有极其显著的抑制作用。在小鼠戊巴比妥钠延长睡眠时间实验和小鼠开野实验中,正丁醇部位浸膏未能延长小鼠戊巴比妥钠引发的睡眠时间和影响受试小鼠的自主活动行为,这些结果表明正丁醇部位浸膏的镇痛活性与催眠作用和破坏脑部运动神经的毒性作用无关,具有特异性。另外,在小鼠福尔马林镇痛药理拮抗实验和小鼠辣椒素镇痛药理拮抗实验中,此镇痛药理活性对药理拮抗工具药纳络酮和格林本脲的拮抗作用不敏感,而完全被尼莫地平的拮抗作用拮抗;表明了正丁醇部位浸膏的镇痛药理活性与L-type Ca~(2+) channels有关。另外,从植物鸡屎藤正丁醇部位分离出多个环烯醚萜苷类和环烯醚萜苷二聚体类化合物,正丁醇部位的镇痛药理活性可能与这些化合物的协同作用有关;至于,在这些化合物中某个化合物是否具有强烈的镇痛药理活性还需进一步深入研究。
应用化学刺激和热刺激引发小鼠疼痛的整体动物模型对植物鸡屎藤甲醇提取物石油醚部位浸膏的镇痛药理活性进行研究。实验结果表明:口服给药剂量为20 mg/kg, 40 mg/kg和80 mg/kg植物鸡屎藤甲醇提取物石油醚部位浸膏的受试小鼠对腹腔注射醋酸溶液、足底皮下注射福尔马林溶液和辣椒素溶液引发的疼痛以及在小鼠热水甩尾实验和小鼠热板实验中对热刺激引发的疼痛均具有良好的耐受性。其中剂量为80 mg/kg的石油醚部位浸膏对化学和热刺激引发的疼痛具有极其显著的抑制作用。在小鼠戊巴比妥钠延长睡眠时间实验和小鼠开野实验中,石油醚部位浸膏未能延长小鼠戊巴比妥钠引发的睡眠时间和影响受试小鼠的自主活动行为,这些结果表明石油醚部位浸膏的镇痛活性与催眠作用和破坏脑部运动神经的毒性作用无关,具有特异性。另外,在小鼠福尔马林镇痛药理拮抗实验和小鼠辣椒素镇痛药理拮抗实验中,此镇痛药理活性对药理拮抗工具药纳络酮的拮抗作用不敏感,而完全被格林本脲的拮抗作用拮抗;表明了石油醚部位浸膏的镇痛药理活性与K~+-ATP channels有关。另外,通过应用GC-MS技术对石油醚部位化学成分进行分析发现其主要化合物为linoleic acid,the sterols和vitamin E。因此,我们推断石油醚部位镇痛药理活性与这些化合物的协同作用有关。
对从植物鸡屎藤醇提物正丁醇部位浸膏中分离出的环烯醚萜苷类和环烯醚萜苷二聚体类化合物,进行了镇痛药理动物模型筛选。结果发现,化合物鸡屎藤苷酸甲酯具有潜在的镇痛药理活性。应用化学刺激和热刺激引发小鼠疼痛的整体动物模型对该单体化合物的镇痛药理活性进行了深入研究。实验结果表明:腹腔注射给药剂量为20 mg/kg,40 mg/kg和60 mg/kg鸡屎藤苷酸甲酯的受试小鼠对腹腔注射醋酸溶液,足底皮下注射福尔马林溶液和辣椒素溶液引发的疼痛以及在小鼠热水甩尾实验和小鼠热板实验中对热刺激引发的疼痛均具有良好的耐受性。其中剂量为60 mg/kg的鸡屎藤苷酸甲酯对化学和热刺激引发的疼痛具有极其显著的抑制作用。在小鼠戊巴比妥钠延长睡眠时间实验和小鼠体内温度测定实验中,该化合物未能延长小鼠戊巴比妥钠引发的睡眠时间和影响受试小鼠的体温改变,这些结果表明鸡屎藤苷酸甲酯的镇痛活性与催眠作用和药物毒性作用无关,具有特异性。另外,在小鼠热板镇痛药理拮抗实验中,此镇痛药理活性对药理拮抗工具药纳络酮和尼莫地平的拮抗作用不敏感,而完全被亚甲基蓝、L-NAME、格林本脲的拮抗作用拮抗;表明了鸡屎藤苷酸甲酯的镇痛药理活性可能与NO-cGMP-K~+-ATP channels途径有关。
Paederia scandens (Lour.) Merri., a climbing plant, belonging to the family Rubiaceae, is popularly known as the name“Ji Shi Teng”in Chinese which is widely grown in China, Japan, India, Philippines and USA. It has been traditionally used as folklore medicine and food in Southeast of Asia for thousands of years. The leaves of the plant are used as an ingredient in various foods in Vietnam.
Recently, it has been reported that the iridoid glycosides and the dimeric iridoid glycosides- paederoside, asperuloside, paederosidic acid, deacetylasperuloside, scandoside were isolated from the MeOH extract from the stems and roots of P. scandens. These chemical constituents of P. scandens have biological activities such as anti-virus, anti-tumor, anti-inflammation and anti-microbial activities. In folklore medicine, the roots, leaves, barks and fruits of P. scandens have been used to treat toothache, chest pain, piles, inflammation of the spleen, diuretic, emetic, rheumatic arthritis and cure bacillary dysentery in China, Japan, Vietnam and other countries in the south-east Asia for thousands of years. Although P. scandens is a particularly useful pain- relief in folklore medicine, there has been no report on the anti-nociceptive activity of this plant and its mechanisms of analgesic activity so far.
Based on investigation above, we study the analgesic activity of the MeOH extracts of P. scandens and the anti-nociceptive activity of the petroleum ether, chloroform, n-butanol and water fractions from the MeOH extracts.
The MeOH extract from Paederia scandens was administered orally and studied on analgesic activity in chemical- and thermal- induced nociception models in mice. In acetic acid-induced writhing test, formalin test and tail-flick test, the significant inhibition of nociception was observed at the doses of 600 and 900 mg/kg. Moreover, the MeOH extract could relieve the central and peripheral nociception in the formalin test.
The n-butanol fraction of the MeOH extract from Paederia scandens was evaluated for antinociceptive activity in mice using chemical and thermal models of nociception. The n-butanol fraction, given orally at doses of 150, 300 and 600 mg/kg produced significant inhibition of chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections, and of thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at a dose of 600 mg/kg. In the pentobarbital sodium-induced sleeping time test and the open-field test, the n-butanol fraction neither significantly enhanced pentobarbital sodium-induced sleeping time nor impaired motor performance, indicating that the observed anti-nociception was unlikely to be due to sedation or motor abnormality. Moreover, the n-butanol fraction-induced anti-nociception in both the capsaicin and formalin tests was insensitive to naloxone or glibenclamide but was significantly antagonized by nimodipine. These results suggest that the n-butanol fraction produced anti-nociception possibly related to nimodipine-sensitive L-type Ca~(2+) channels, which merits further studies regarding the precise site and mechanism of action. Furthermore, iridoid glycosides isolated from the n-butanol fraction might be related to its antinociceptive action fraction. Therefore, the effect on analgesic activity of each chemical compound in large quantity might well be considered in a further study.
The petroleum ether fraction of MeOH extract from Paederia scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception. Given orally, the petroleum ether fraction (PEF) at doses of 20, 40 and 80 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 80 mg/kg of the petroleum ether fraction. In the pentobarbital sodium-induced sleeping time test and the open-field test, the petroleum ether fraction neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality. Moreover, the petroleum ether fraction-induced anti-nociception in both capsaicin and formalin tests was insensitive to naloxone, but was significantly antagonized by glibenclamide. These results suggested that the petroleum ether fraction produced anti-nociception possibly related to glibenclamide-sensitive K~+-ATP channels, which merited further studies regarding the precise site and mechanism of action. The major constituents of the petroleum ether fraction (PEF) determined by GC/MS analysis, are linoleic acid, the sterols and vitamin E. Therefore it can be suggested that they exert synergetic effects and are together responsible for the antinociceptive activity of the PEF-fraction.
We test the anti-nociceptive activity of iridoid glycosides isolated from the n-butanol fraction of the MeOH extract from Paederia scandens. Then we found the paederosidic acid methyl ester showed the potential anti-nociception. This iridoid glycoside was evaluated for anti-nociceptive activity in mice using chemical and thermal models of nociception. The paederosidic acid methyl ester, given intraperitoneal injection at doses of 20, 40 and 60 mg/kg, produced significant inhibition of chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections, and of thermal nociception both in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at a dose of 60 mg/kg. In the pentobarbital sodium-induced sleeping time test and the measurement of core body temperature, the chemical compound neither significantly enhanced pentobarbital sodium-induced sleeping time nor influent the temperature of core body, indicating that the observed anti-nociception was unlikely to be due to sedation or toxicity. Moreover, the paederosidic acid methyl ester -induced anti-nociception in the hot-pate test was insensitive to naloxone or nimodipine, but was significantly antagonized by methylene blue, L-NAME and glibenclamide. These results suggest that the paederosidic acid methyl ester produced anti-nociception possibly related to the anti-nociception pathway- NO-cGMP-K~+-ATP, which merits further studies regarding the precise site and mechanism of action.
引文
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