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Alkaloids from Lime Flower (Tiliae flos) Exert Spasmodic Activity on Murine Airway Smooth Muscle Involving Acetylcholinesterase
Planta Medica ( IF 2.1 ) Pub Date : 2021-07-16 , DOI: 10.1055/a-1534-3766
Alexander Hake 1, 2 , Nico Symma 2 , Stefan Esch 2 , Andreas Hensel 2 , Martina Düfer 1
Affiliation  

Lime flower (Tiliae flos) is traditionally used either for treatment of the common cold or to relieve symptoms of mental stress. Recently, the presence of a new class of piperidine and dihydro-pyrrole alkaloids from lime flower has been described. The present study aimed to investigate the pharmacological activity of hydroacetonic lime flower extracts, alkaloid-enriched lime flower fractions, and isolated alkaloids on the murine airway smooth muscle and the cholinergic system. While a hydroacetonic lime flower extract did not show any pharmacological activity, enriched Tilia alkaloid fractions potentiated acetylcholine-induced contractions of the trachea by ~ 30%, showing characteristics comparable to galanthamine. Effects were abrogated by atropine, indicating an involvement of muscarinic receptors. The dihydro-pyrrole alkaloid tiliine A, the piperidine alkaloid tiliamine B, and the acetylated piperidine alkaloid tilacetine A were characterized as acetylcholinesterase inhibitors. The positive control galanthamine (IC50 = 2.0 µM, 95% CI 1.7 to 2.2 µM) was approximately 100 times more potent compared to tiliine A (IC50 = 237 µM, 95% CI 207 to 258 µM) and tiliamine B (IC50 = 172 µM, 95% CI 158 to 187 µM). Neither DNA synthesis of HepG2 liver cells, HaCaT keratinocytes, and Caco-2 intestinal epithelial cells nor cell viability of primary human fibroblasts was reduced by the alkaloids. The indirect cholinergic activity of the alkaloids might explain some aspects of the traditional use of lime flowers and may extend the portfolio of compounds with regard to diseases involving parasympathetic malfunction or central cholinergic imbalance.

中文翻译:

来自石灰花 (Tiliae flos) 的生物碱对涉及乙酰胆碱酯酶的小鼠气道平滑肌具有痉挛活性

石灰花 (Tiliae flos) 传统上用于治疗普通感冒或缓解精神压力症状。最近,已经描述了来自石灰花的一类新的哌啶和二氢吡咯生物碱的存在。本研究旨在研究水丙酮酸橙花提取物、富含生物碱的酸橙花组分和分离的生物碱对小鼠气道平滑肌和胆碱能系统的药理活性。虽然水丙酮酸橙花提取物没有显示出任何药理活性,但富集的椴树生物碱组分可将乙酰胆碱诱导的气管收缩增强约 30%,显示出与加兰他敏相当的特性。阿托品消除了影响,表明毒蕈碱受体的参与。二氢吡咯生物碱替林A,哌啶生物碱替拉胺B和乙酰化哌啶生物碱替拉西汀A被表征为乙酰胆碱酯酶抑制剂。阳性对照加兰他敏 (IC50 = 2.0 µM, 95% CI 1.7 至 2.2 µM) 的效力大约是硫胺 A (IC50 = 237 µM, 95% CI 207 至 258 µM) 和硫胺 B (IC50 = 172 µM) 的 100 倍, 95% CI 158 至 187 µM)。HepG2 肝细胞、HaCaT 角质形成细胞和 Caco-2 肠上皮细胞的 DNA 合成以及原代人成纤维细胞的细胞活力均未因生物碱而降低。生物碱的间接胆碱能活性可能解释了传统使用酸橙花的某些方面,并可能扩展涉及副交感神经功能障碍或中枢胆碱能失衡的疾病的化合物组合。乙酰化哌啶生物碱 tilacetine A 被表征为乙酰胆碱酯酶抑制剂。阳性对照加兰他敏 (IC50 = 2.0 µM, 95% CI 1.7 至 2.2 µM) 的效力大约是硫胺 A (IC50 = 237 µM, 95% CI 207 至 258 µM) 和硫胺 B (IC50 = 172 µM) 的 100 倍, 95% CI 158 至 187 µM)。HepG2 肝细胞、HaCaT 角质形成细胞和 Caco-2 肠上皮细胞的 DNA 合成以及原代人成纤维细胞的细胞活力均未因生物碱而降低。生物碱的间接胆碱能活性可能解释了传统使用酸橙花的某些方面,并可能扩展涉及副交感神经功能障碍或中枢胆碱能失衡的疾病的化合物组合。乙酰化哌啶生物碱 tilacetine A 被表征为乙酰胆碱酯酶抑制剂。阳性对照加兰他敏 (IC50 = 2.0 µM, 95% CI 1.7 至 2.2 µM) 的效力大约是硫胺 A (IC50 = 237 µM, 95% CI 207 至 258 µM) 和硫胺 B (IC50 = 172 µM) 的 100 倍, 95% CI 158 至 187 µM)。HepG2 肝细胞、HaCaT 角质形成细胞和 Caco-2 肠上皮细胞的 DNA 合成以及原代人成纤维细胞的细胞活力均未因生物碱而降低。生物碱的间接胆碱能活性可能解释了传统使用酸橙花的某些方面,并可能扩展涉及副交感神经功能障碍或中枢胆碱能失衡的疾病的化合物组合。阳性对照加兰他敏 (IC50 = 2.0 µM, 95% CI 1.7 至 2.2 µM) 的效力大约是硫胺 A (IC50 = 237 µM, 95% CI 207 至 258 µM) 和硫胺 B (IC50 = 172 µM) 的 100 倍, 95% CI 158 至 187 µM)。HepG2 肝细胞、HaCaT 角质形成细胞和 Caco-2 肠上皮细胞的 DNA 合成以及原代人成纤维细胞的细胞活力均未因生物碱而降低。生物碱的间接胆碱能活性可能解释了传统使用酸橙花的某些方面,并可能扩展涉及副交感神经功能障碍或中枢胆碱能失衡的疾病的化合物组合。阳性对照加兰他敏 (IC50 = 2.0 µM, 95% CI 1.7 至 2.2 µM) 的效力大约是硫胺 A (IC50 = 237 µM, 95% CI 207 至 258 µM) 和硫胺 B (IC50 = 172 µM) 的 100 倍, 95% CI 158 至 187 µM)。HepG2 肝细胞、HaCaT 角质形成细胞和 Caco-2 肠上皮细胞的 DNA 合成以及原代人成纤维细胞的细胞活力均未因生物碱而降低。生物碱的间接胆碱能活性可能解释了传统使用酸橙花的某些方面,并可能扩展涉及副交感神经功能障碍或中枢胆碱能失衡的疾病的化合物组合。95% CI 207 至 258 µM)和硫胺 B(IC50 = 172 µM,95% CI 158 至 187 µM)。HepG2 肝细胞、HaCaT 角质形成细胞和 Caco-2 肠上皮细胞的 DNA 合成以及原代人成纤维细胞的细胞活力均未因生物碱而降低。生物碱的间接胆碱能活性可能解释了传统使用酸橙花的某些方面,并可能扩展涉及副交感神经功能障碍或中枢胆碱能失衡的疾病的化合物组合。95% CI 207 至 258 µM)和硫胺 B(IC50 = 172 µM,95% CI 158 至 187 µM)。HepG2 肝细胞、HaCaT 角质形成细胞和 Caco-2 肠上皮细胞的 DNA 合成以及原代人成纤维细胞的细胞活力均未因生物碱而降低。生物碱的间接胆碱能活性可能解释了传统使用酸橙花的某些方面,并可能扩展涉及副交感神经功能障碍或中枢胆碱能失衡的疾病的化合物组合。
更新日期:2021-07-21
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