Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
BMC Complement Altern Med. 2014 Feb 20;14:63. doi: 10.1186/1472-6882-14-63.
Muntingia calabura (Elaecoparceae) is a medicinal plant traditionally used, particularly, by the Peruvian people to alleviate headache and cold, pain associated with gastric ulcers or to reduce the prostate gland swelling. Following the recent establishment of antinociceptive activity of M. calabura leaf, the present study was performed to further elucidate on the possible mechanisms of antinociception involved.
The methanol extract of M. calabura (MEMC) was prepared in the doses of 100, 250 and 500 mg/kg. The role of bradykinin, protein kinase C, pottasium channels, and various opioid and non-opioid receptors in modulating the extract's antinociceptive activity was determined using several antinociceptive assays. Results are presented as Mean ± standard error of mean (SEM). The one-way ANOVA test with Dunnett's multiple comparison was used to analyze and compare the data, with P < 0.05 as the limit of significance.
The MEMC, at all doses, demonstrated a significant (p < 0.05) dose-dependent antinociceptive activity in both the bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced nociception. Pretreatment of the 500 mg/kg MEMC with 10 mg/kg glibenclamide (an ATP-sensitive K+ channel inhibitor), the antagonist of μ-, δ- and κ-opioid receptors (namely 10 mg/kg β-funaltrexamine, 1 mg/kg naltrindole and 1 mg/kg nor-binaltorphimine), and the non-opioid receptor antagonists (namely 3 mg/kg caffeine (a non-selective adenosinergic receptor antagonist), 0.15 mg/kg yohimbine (an α2-noradrenergic antagonist), and 1 mg/kg pindolol (a β-adrenoceptor antagonist)) significantly (p < 0.05) reversed the MEMC antinociception. However, 10 mg/kg atropine (a non-selective cholinergic receptor antagonist), 0.15 mg/kg prazosin (an α1-noradrenergic antagonist) and 20 mg/kg haloperidol (a non-selective dopaminergic antagonist) did not affect the extract's antinociception. The phytochemicals screening revealed the presence of saponins, flavonoids, tannins and triterpenes while the HPLC analysis showed the presence of flavonoid-based compounds.
The antinociceptive activity of MEMC involved activation of the non-selective opioid (particularly the μ-, δ- and κ-opioid) and non-opioid (particularly adenosinergic, α2-noradrenergic, and β-adrenergic) receptors, modulation of the ATP-sensitive K+ channel, and inhibition of bradikinin and protein kinase C actions. The discrepancies in MEMC antinociception could be due to the presence of various phytochemicals.
五敛子（藤黄科）是一种传统的药用植物，特别是被秘鲁人用来缓解头痛和感冒，缓解胃溃疡引起的疼痛或减轻前列腺肿胀。最近发现五敛子叶具有抗伤害感受作用，本研究进一步探讨了其可能涉及的镇痛机制。
用甲醇提取五敛子（MEMC），剂量为 100、250 和 500mg/kg。使用几种镇痛测定法，确定缓激肽、蛋白激酶 C、钾通道以及各种阿片类和非阿片类受体在调节提取物的镇痛活性中的作用。结果表示为均值±标准误差（SEM）。采用单因素方差分析（one-way ANOVA）和 Dunnett 多重比较检验对数据进行分析和比较，以 P<0.05 为显著性界限。
MEMC 在所有剂量下均表现出显著的（p<0.05）剂量依赖性镇痛作用，在缓激肽和佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导的疼痛中均如此。用 10mg/kg 格列本脲（一种 ATP 敏感性钾通道抑制剂）预处理 500mg/kg MEMC，用 μ-、δ-和 κ-阿片受体拮抗剂（即 10mg/kg β-氟纳曲胺、1mg/kg 纳曲吲哚和 1mg/kg 去甲二氢吗啡酮）以及非阿片受体拮抗剂（即 3mg/kg 咖啡因（一种非选择性腺苷能受体拮抗剂）、0.15mg/kg 育亨宾（一种α2-去甲肾上腺素能拮抗剂）和 1mg/kg 普萘洛尔（一种β-肾上腺素受体拮抗剂））预处理，可显著（p<0.05）逆转 MEMC 的镇痛作用。然而，10mg/kg 阿托品（一种非选择性胆碱能受体拮抗剂）、0.15mg/kg 哌唑嗪（一种α1-去甲肾上腺素能拮抗剂）和 20mg/kg 氟哌啶醇（一种非选择性多巴胺拮抗剂）对提取物的镇痛作用没有影响。植物化学物质筛选显示存在皂甙、类黄酮、单宁和三萜，HPLC 分析显示存在基于类黄酮的化合物。
MEMC 的镇痛活性涉及非选择性阿片类（特别是μ-、δ-和 κ-阿片类）和非阿片类（特别是腺苷能、α2-去甲肾上腺素能和 β-肾上腺素能）受体的激活、ATP 敏感性钾通道的调节以及缓激肽和蛋白激酶 C 作用的抑制。MEMC 镇痛作用的差异可能是由于存在各种植物化学物质。
