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药用黄荆气道平滑肌松弛作用主要与增加环磷酸腺苷和抑制钙通道有关。

Airway smooth muscle relaxant activity of Cordia dodecandra A. DC. mainly by cAMP increase and calcium channel blockade.

机构信息

Laboratorio de Farmacología, Facultad de Química, Universidad Autónoma de Yucatán, Calle 43 No. 613 x calle 90, Colonia Inalámbrica, C.P. 97069 Mérida, Yucatán, Mexico.

Laboratorio de Cromatografía, Facultad de Química, Universidad Autónoma de Yucatán, Calle 43 No. 613 x calle 90, Colonia Inalámbrica, C.P. 97069 Mérida, Yucatán, Mexico.

出版信息

J Ethnopharmacol. 2019 Jan 30;229:280-287. doi: 10.1016/j.jep.2018.10.013. Epub 2018 Oct 17.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The fight against chronic respiratory diseases needs the exploration of new active compounds with properties that contribute to diminish the symptoms or resolve the disease alongside current therapy.

MATERIALS AND METHODS

Eight extracts obtained from the bark and leaves of a Mayan medicinal plant used to treat asthma, Cordia dodecandra A. DC., were investigated for their relaxant effect on rat isolated tracheal rings pre-contracted with carbachol [1 µM]. The underlying functional mode of action of the most effective extract was assessed and the chromatographic fingerprints of more active extracts were analyzed.

RESULTS

The dichloromethane bark extract (DECd-b) was the most effective and potent (E= 87.57 ± 1.32 %; EC = 392.7 ± 5.18 µg/mL). DECd-b relaxant effect was maximized in presence of isoproterenol (β-adrenergic agonist, [10 µM]) and theophylline (phosphodiesterase unspecific inhibitor, [10 µM]). DECd-b also showed efficient relaxation of KCl [80 mM]-induced contraction and inhibition of CaCl-induced contraction. Pre-incubation with propranolol (non-selective β-adrenergic antagonist, [10 µM]), SQ22536 (adenylyl cyclase inhibitor; [100 µM]), ODQ (guanylyl cyclase inhibitor; [10 µM]), l-NAME (nitric oxide synthase inhibitor; [10 µM]), indomethacin (a cyclooxygenase unspecific inhibitor; [10 µM]), glibenclamide (ATP-sensitive potassium channel blocker; [10 µM]) and 2-aminopyridine (voltage-gated potassium channel blocker [100 µM]) did not modify the DECd-b relaxant-effect curve. The chromatographic analysis of DECd-b suggests the cordiaquinones presence with double conjugated bounds such as menaquinone.

CONCLUSIONS

Results suggest that DECd-b induces relaxation mainly by cAMP increase and Ca channel blockade. The chromatographic profiles and UV spectrum of DECd-b and HECd-l suggest the presence of molecules with structure of meroterpenoid naphthoquinones. This work report scientific evidence of C. dodecandra medicinal specie, which contributes to the pharmacological and phytochemical background of C. dodecandra providing an added value to the traditional use of this specie.

摘要

民族药理学相关性

与慢性呼吸道疾病作斗争需要探索具有减轻症状或解决疾病的特性的新活性化合物,以补充当前的治疗方法。

材料与方法

对用于治疗哮喘的玛雅药用植物 Cordia dodecandra A. DC 的树皮和叶子提取物进行了研究,以评估其对预先用卡巴胆碱[1 μM]收缩的大鼠分离气管环的松弛作用。评估了最有效提取物的潜在功能作用模式,并分析了更活跃提取物的色谱指纹图谱。

结果

二氯甲烷树皮提取物(DECd-b)是最有效和最有效的(E = 87.57 ± 1.32%;EC = 392.7 ± 5.18μg/mL)。在异丙肾上腺素(β-肾上腺素能激动剂,[10 μM])和茶碱(磷酸二酯酶非特异性抑制剂,[10 μM])存在的情况下,DECd-b 的松弛作用达到最大。DECd-b 还显示出对 KCl [80 mM]诱导收缩的有效松弛作用和对 CaCl 诱导收缩的抑制作用。用普萘洛尔(非选择性β-肾上腺素能拮抗剂,[10 μM])、SQ22536(腺苷酸环化酶抑制剂;[100 μM])、ODQ(鸟苷酸环化酶抑制剂;[10 μM])、l-NAME(一氧化氮合酶抑制剂;[10 μM])、吲哚美辛(非甾体环氧化酶抑制剂;[10 μM])、格列本脲(ATP 敏感性钾通道阻滞剂;[10 μM])和 2-氨基吡啶(电压门控钾通道阻滞剂[100 μM])预处理不会改变 DECd-b 的松弛效应曲线。DECd-b 的色谱分析表明存在具有双键的 cordiaquinones,例如menaquinone。

结论

结果表明,DECd-b 主要通过 cAMP 增加和钙通道阻断来诱导松弛。DECd-b 和 HECd-l 的色谱图和紫外光谱表明存在具有萘醌型倍半萜结构的分子。这项工作为 C. dodecandra 药用种提供了科学依据,为 C. dodecandra 的药理学和植物化学背景做出了贡献,为该种的传统用途提供了附加值。

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