通过体外、体内和计算机技术研究藏边蔷薇在腹泻和哮喘中的民族药理学基础和药效学前景
2023/09/21
摘要
民族药理学相关性：南亚草药师采用藏边蔷薇（蔷薇科）治疗胃肠道和呼吸系统疾病。
目的：本研究旨在通过多个靶点验证藏边蔷薇治疗腹泻和哮喘。本研究拟通过体外、体内和计算机实验证明藏边蔷薇的解痉和舒张支气管的潜力。
材料和方法：采用LC-ESI-MS/MS和高效液相色谱法鉴定和定量了藏边蔷薇的生物活性化合物。网络药理学和分子对接预测了这些化合物具有多种舒张支气管和抗痉挛的潜力。体外实验（分离兔气管、膀胱和空肠组织）证实了上述抗痉挛和舒张支气管的多种机制。体内实验证实了上述抗蠕动、止腹泻和抗分泌作用。
结果：植物化学分析表明，藏边蔷薇中存在芦丁（742.91μg/g）、山奈酚（726.32μg/g）和槲皮苷（688.20μg/g）。这些网络药理学中的生物活性化合物干扰腹泻和哮喘的致病基因，上述基因为钙介导的信号通路的成员，分子对接证明其与电压门控L型钙通道、肌球蛋白轻链激酶、钙钙调蛋白依赖性激酶、磷酸二酯酶-4和磷酸肌醇磷脂酶C之间具有较强的结合亲和力。通过舒张K+（80 mM）和CCh（1μM）痉挛性收缩，藏边蔷薇在离体空肠、气管和尿液制剂中引起解痉反应。此外，藏边蔷薇可像维拉帕米一样抑制钙浓度-反应曲线右移。藏边蔷薇可像双环胺一样引起CCh曲线向右平移，进而在较高浓度下发生非平行移动，从而抑制最大效应。藏边蔷薇也可像罂粟碱一样导致异丙肾上腺素诱导的抑制性CRC向左移动。维拉帕米不能增强异丙肾上腺素诱导的抑制性CRC，尽管它对K+（80 mM）诱导的收缩比CCh（1μM）诱导的收缩更有效。体内实验中藏边蔷薇提取物（300 mg/kg）表现出完全的抗蠕动（21.55%）、止泻（80.33%）和抗分泌（82.59±0.60）活性。
结论：因此，藏边蔷薇可通过调控多种通路，产生钙拮抗、抗胆碱能和抑制磷酸二酯酶的作用，并具有止泻和舒张支气管的作用。
Ethnopharmacological basis and pharmacodynamics prospectives for folkloric claims of Rosa webbiana wall. Ex. Royle in diarrhea and asthma via In vitro, In vivo and In silico techniques
Anam Ali, Fatima Saqib
Abstract
Ethnopharmacological relevance:Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders.
Aim of the study:This research aimed at multiple targets to verify R. webbiana for treating diarrhea and asthma. In vitro, in vivo, and in silico experiments were planned to demonstrate the antispasmodic and bronchodilator potential of R. webbiana.
Materials and methods:The bioactive compounds of R. webbiana were identified and quantified through LC ESI-MS/MS and HPLC. These compounds were predicted for muti-mechanisms of bronchodilator and antispasmodic potential in network pharmacology and molecular docking. In vitro methods (isolated rabbit trachea, bladder, and jejunum tissues) confirmed these multi-mechanisms for antispasmodic and bronchodilator effects. Antiperistalsis, antidiarrheal, and antisecretory experiments were conducted in in-vivo experiments.
RESULTS:The phytochemical analysis indicates the presence of rutin (742.91 μg/g), kaempferol (726.32 μg/g), and quercitrin (688.20 μg/g) in Rw. EtOH. These bioactive compounds in network pharmacology interfere with the pathogenic genes of diarrhea and asthma, which are the members of calcium-mediated signaling pathways and showed the stronger binding affinity towards voltage-gated L-type calcium channels, myosin light chain-kinase, Calcium calmodulin-dependent-kinase, Phosphodiesterase-4, and phosphoinositide phospholipase-C in molecular docking. Rw. EtOH elicited a spasmolytic response in isolated jejunum, trachea, and urine preparations by relaxing K+ (80 mM) and CCh (1 μM) spastic contractions. Additionally, it suppressed calcium concentration-response curves to the right, like verapamil. Like dicyclomine, it caused a rightward parallel shift of the CCh curves, followed by a non-parallel shift at higher concentrations with suppression of the maximal response. Like papaverine, it also caused isoprenaline-induced inhibitory CRCs to shift to the left. Verapamil did not potentiate isoprenaline-induced inhibitory CRCs, although it was more efficacious against K+ (80 mM) than CCh (1 μM)-induced contractions. R. webbiana EtOH extract exhibited complete antiperistalsis (21.55%), antidiarrheal (80.33%), and antisecretory (82.59±0.60) activities in vivo experiments at the dose of 300 mg/kg.
CONCLUSION:Thus, Rw. EtOH modulated multiple pathways, produced calcium antagonistic, anticholinergic, and phosphodiesterase inhibitory actions, and had antidiarrheal and bronchodilator effects.
民族药理学相关性：南亚草药师采用藏边蔷薇（蔷薇科）治疗胃肠道和呼吸系统疾病。
目的：本研究旨在通过多个靶点验证藏边蔷薇治疗腹泻和哮喘。本研究拟通过体外、体内和计算机实验证明藏边蔷薇的解痉和舒张支气管的潜力。
材料和方法：采用LC-ESI-MS/MS和高效液相色谱法鉴定和定量了藏边蔷薇的生物活性化合物。网络药理学和分子对接预测了这些化合物具有多种舒张支气管和抗痉挛的潜力。体外实验（分离兔气管、膀胱和空肠组织）证实了上述抗痉挛和舒张支气管的多种机制。体内实验证实了上述抗蠕动、止腹泻和抗分泌作用。
结果：植物化学分析表明，藏边蔷薇中存在芦丁（742.91μg/g）、山奈酚（726.32μg/g）和槲皮苷（688.20μg/g）。这些网络药理学中的生物活性化合物干扰腹泻和哮喘的致病基因，上述基因为钙介导的信号通路的成员，分子对接证明其与电压门控L型钙通道、肌球蛋白轻链激酶、钙钙调蛋白依赖性激酶、磷酸二酯酶-4和磷酸肌醇磷脂酶C之间具有较强的结合亲和力。通过舒张K+（80 mM）和CCh（1μM）痉挛性收缩，藏边蔷薇在离体空肠、气管和尿液制剂中引起解痉反应。此外，藏边蔷薇可像维拉帕米一样抑制钙浓度-反应曲线右移。藏边蔷薇可像双环胺一样引起CCh曲线向右平移，进而在较高浓度下发生非平行移动，从而抑制最大效应。藏边蔷薇也可像罂粟碱一样导致异丙肾上腺素诱导的抑制性CRC向左移动。维拉帕米不能增强异丙肾上腺素诱导的抑制性CRC，尽管它对K+（80 mM）诱导的收缩比CCh（1μM）诱导的收缩更有效。体内实验中藏边蔷薇提取物（300 mg/kg）表现出完全的抗蠕动（21.55%）、止泻（80.33%）和抗分泌（82.59±0.60）活性。
结论：因此，藏边蔷薇可通过调控多种通路，产生钙拮抗、抗胆碱能和抑制磷酸二酯酶的作用，并具有止泻和舒张支气管的作用。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(J Ethnopharmacol. 2023 Dec 5;317:116696. doi: 10.1016/j.jep.2023.116696.)
(J Ethnopharmacol. 2023 Dec 5;317:116696. doi: 10.1016/j.jep.2023.116696.)
Ethnopharmacological basis and pharmacodynamics prospectives for folkloric claims of Rosa webbiana wall. Ex. Royle in diarrhea and asthma via In vitro, In vivo and In silico techniques
Anam Ali, Fatima Saqib
Abstract
Ethnopharmacological relevance:Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders.
Aim of the study:This research aimed at multiple targets to verify R. webbiana for treating diarrhea and asthma. In vitro, in vivo, and in silico experiments were planned to demonstrate the antispasmodic and bronchodilator potential of R. webbiana.
Materials and methods:The bioactive compounds of R. webbiana were identified and quantified through LC ESI-MS/MS and HPLC. These compounds were predicted for muti-mechanisms of bronchodilator and antispasmodic potential in network pharmacology and molecular docking. In vitro methods (isolated rabbit trachea, bladder, and jejunum tissues) confirmed these multi-mechanisms for antispasmodic and bronchodilator effects. Antiperistalsis, antidiarrheal, and antisecretory experiments were conducted in in-vivo experiments.
RESULTS:The phytochemical analysis indicates the presence of rutin (742.91 μg/g), kaempferol (726.32 μg/g), and quercitrin (688.20 μg/g) in Rw. EtOH. These bioactive compounds in network pharmacology interfere with the pathogenic genes of diarrhea and asthma, which are the members of calcium-mediated signaling pathways and showed the stronger binding affinity towards voltage-gated L-type calcium channels, myosin light chain-kinase, Calcium calmodulin-dependent-kinase, Phosphodiesterase-4, and phosphoinositide phospholipase-C in molecular docking. Rw. EtOH elicited a spasmolytic response in isolated jejunum, trachea, and urine preparations by relaxing K+ (80 mM) and CCh (1 μM) spastic contractions. Additionally, it suppressed calcium concentration-response curves to the right, like verapamil. Like dicyclomine, it caused a rightward parallel shift of the CCh curves, followed by a non-parallel shift at higher concentrations with suppression of the maximal response. Like papaverine, it also caused isoprenaline-induced inhibitory CRCs to shift to the left. Verapamil did not potentiate isoprenaline-induced inhibitory CRCs, although it was more efficacious against K+ (80 mM) than CCh (1 μM)-induced contractions. R. webbiana EtOH extract exhibited complete antiperistalsis (21.55%), antidiarrheal (80.33%), and antisecretory (82.59±0.60) activities in vivo experiments at the dose of 300 mg/kg.
CONCLUSION:Thus, Rw. EtOH modulated multiple pathways, produced calcium antagonistic, anticholinergic, and phosphodiesterase inhibitory actions, and had antidiarrheal and bronchodilator effects.
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