Centro de Investigación Biomédica Del Sur, Instituto Mexicano Del Seguro Social (IMSS), Argentina 1, 62790, Xochitepec, Morelos, Mexico; Doctorado en Ciencias Biológicas y de La Salud, División de Ciencias Biológicas y de La Salud, Universidad Autónoma Metropolitana (UAM), México City, Mexico; Departamento de Ciencias de La Salud, División de Ciencias Biológicas y de La Salud, Universidad Autónoma Metropolitana- Iztapalapa, Av. San Rafael Atlixco No.186, Col. Vicentina C.P.09340, Iztapalapa, México D.F, Mexico.
Centro de Investigación Biomédica Del Sur, Instituto Mexicano Del Seguro Social (IMSS), Argentina 1, 62790, Xochitepec, Morelos, Mexico.
J Ethnopharmacol. 2021 Mar 1;267:113619. doi: 10.1016/j.jep.2020.113619. Epub 2020 Nov 25.
The aerial parts of Tilia americana var. mexicana (Malvaceae, formerly Tiliaceae) or "sirimo" are used in Mexican traditional medicine for the relief of mild symptoms of mental stress, commonly referred to as "nerve diseases". Individuals use this plant to fall asleep, to calm states of nervous excitement, headaches, mood disorders, and general discomfort. Recent studies indicated that fractions standardized in their flavonoid content possess antidepressant activity in behavioral assays in mice. The present study aims to focus on the evaluation of the antidepressant effect of the mixture of two flavonoids (FMix), and its interaction with serotonergic drugs. Also, the pharmacological effect of the products of the metabolism of aglycone, quercetin, was evaluated in mice subjected to forced swimming test (FST) and open field test (OFT).
A methanol-soluble extract obtained from leaves of Tilia americana was fractionated in an open column chromatographic separation. One of the fractions contained FMix wich is constituted of the mixture of quercetin 4'-O-rhamnoside (1, 47%) y isoquercitrin (2, 53%). The mice were divided into the several following groups: FMix (0.01, 0.1, 0.5, 1.0, and 2 mg/kg); FMix (1.0 mg/kg) and agonist DOI (2.0 mg/kg); FMix (1.0 mg/kg) and antagonist ketanserin (KET, 0.03 mg/kg) of 5-HT2A receptors; FMix (1.0 mg/kg) and selective agonist 8-OH-DPAT (8-OH, 0.01 mg/kg); FMix (1.0 mg/kg) and antagonist WAY100635 (WAY, 0.5 mg/kg) of 5HT1 receptors; Phloroglucinol (PHL); 3,4-dihydroxy-phenyl acid (DOPAC); p-hydroxyphenyl acetic acid (p-HPAA); and m-hydroxyphenyl acetic acid (m-HPAA) were tested in FST or OFT.
FMix induced dependent-dose antidepressant activity and, at the highest dose administered, a sedative effect was also observed. The 8-OH-DPAT, or the DOI, or the KET combination with FMix (1.0 mg/kg) induced a higher antidepressant effect than compounds alone; there was no effect exerted with WAY. The activity on OFT increased only with the FMix and KET combination. At the same time, the products of the aglycone metabolism of quercetin, that is, DOPAC and p-HPAA, decreased the immobility time of the mice in FST at 1.0 mg/kg, and a dose-curve was formed for these.
The antidepressant effect of FMix could depend, at least in part, on the degradation products of quercetin and with a possible action mode through interaction with the serotoninergic system.
墨西哥美国椴树（锦葵科，前椴树科）或“sirimo”的地上部分在墨西哥传统医学中用于缓解轻度精神压力症状，通常称为“神经疾病”。个体使用这种植物入睡，以平静兴奋状态，头痛，情绪障碍和一般不适。最近的研究表明，标准化在其类黄酮含量的馏分在小鼠行为测定中具有抗抑郁活性。本研究旨在重点评估两种类黄酮混合物（FMix）的抗抑郁作用及其与 5-羟色胺能药物的相互作用。此外，还评估了橙皮苷苷元代谢产物槲皮素在强迫游泳试验（FST）和旷场试验（OFT）中对小鼠的药理学作用。
从美国椴树的叶子中获得的甲醇可溶提取物在开放柱色谱分离中进行了分离。其中一个馏分含有 FMix，它由槲皮素 4'-O-鼠李糖苷（1，47％）和异槲皮苷（2，53％）组成。将小鼠分为以下几组：FMix（0.01、0.1、0.5、1.0 和 2mg/kg）；FMix（1.0mg/kg）和激动剂 DOI（2.0mg/kg）；FMix（1.0mg/kg）和 5-HT2A 受体拮抗剂 KET（0.03mg/kg）；FMix（1.0mg/kg）和选择性激动剂 8-OH-DPAT（8-OH，0.01mg/kg）；FMix（1.0mg/kg）和 5-HT1 受体拮抗剂 WAY100635（WAY，0.5mg/kg）；根皮苷；3,4-二羟基苯乙酸（DOPAC）；对羟基苯乙酸（p-HPAA）；和间羟基苯乙酸（m-HPAA）在 FST 或 OFT 中进行了测试。
FMix 诱导了依赖剂量的抗抑郁作用，并且在给予最高剂量时，还观察到镇静作用。8-OH-DPAT、DOI 或 KET 与 FMix（1.0mg/kg）联合使用比单独使用化合物具有更高的抗抑郁作用；WAY 没有作用。仅 FMix 和 KET 联合使用可增加对 OFT 的作用。同时，橙皮苷苷元代谢产物槲皮素的产物，即 DOPAC 和 p-HPAA，在 1.0mg/kg 时降低了 FST 中小鼠的不动时间，并形成了剂量曲线。
FMix 的抗抑郁作用可能至少部分依赖于槲皮素的降解产物，并且可能通过与 5-羟色胺能系统相互作用而具有作用模式。
