University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Corrensstrasse 48, D-48149, Münster, Germany.
University of Münster, Institute of Pharmaceutical and Medicinal Chemistry, Corrensstrasse 48, D-48149, Münster, Germany.
J Ethnopharmacol. 2019 May 23;236:326-335. doi: 10.1016/j.jep.2019.03.022. Epub 2019 Mar 12.
Leaves and twigs from Phyllanthus muellerianus Kuntze Excell are known to exert anti-inflammatory and antipyretic properties as well as wound healing properties. During a wide screening for human hyaluronidase-1 inhibitors from natural sources leaf extracts from P. muellerianus turned out to show basic anti-hyaluronidase activity. A detailed investigation of this effect should rationalize the potential anti-inflammatory activity of the extract for improved wound healing.
The following study aimed to characterize the anti-Hyal-1 activity of the extract from P. muellerianus and to pinpoint the responsible natural products responsible for this bioactivity.
Using cell surface displayed human Hyal-1 on Escherichia coli, the activity of inhibitors was determined by the stains-all assay method. A hydroalcoholic extract PWE from P. muellerianus was subjected to bioactivity-guided fractionation. Active compounds were characterized by means of mass spectrometry and NMR.
PWE exerts a concentration dependent inhibition of Hyal-1 with an IC of 80 μg/mL. Bioassay-guided fractionation revealed 13 compounds from the two most active fractions, mainly ellagitannins and flavonoid glycosides. The most activeHyal-1 inhibitor was found to be the ellagitannin chebulanin 10 (IC 132 μM). This represents the first description of chebulanin in P. muellerianus.
The hydroalcoholic extract of P. muellerianus, as well as several subfractions obtained during bioassay-guided fractionation showed strong activity against Hyal-1. The main activity can be correlated to the ellagitanin chebulanin. Additionally, also synergistic effects are observed, indicating that the traditional use of aqueous extracts of P. muellerianus is justified, rather than the use of the isolated tannins. The traditional use of the plant as an anti-inflammatory agent for improved wound-healing can be rationalized by the anti-Hyal-1 activities of its constituents.
已知叶和小枝 Phyllanthus muellerianus Kuntze Excell 具有抗炎、解热和伤口愈合特性。在从天然来源筛选人透明质酸酶 1 抑制剂的广泛研究中，发现 P. muellerianus 的叶提取物具有基本的抗透明质酸酶活性。对这种作用的详细研究应该可以使提取物具有抗炎活性，从而改善伤口愈合。
本研究旨在表征 P. muellerianus 提取物的抗 Hyal-1 活性，并确定负责这种生物活性的天然产物。
利用大肠杆菌表面展示的人 Hyal-1，通过染色法测定抑制剂的活性。对 P. muellerianus 的水醇提取物 PWE 进行基于生物活性的分级分离。通过质谱和 NMR 对活性化合物进行表征。
PWE 对 Hyal-1 表现出浓度依赖性抑制作用，IC 50 为 80μg/mL。基于生物活性的分级分离揭示了来自两个最活跃级分的 13 种化合物，主要是鞣花单宁和黄酮糖苷。最活跃的 Hyal-1 抑制剂被发现是鞣花单宁 chebulanin 10（IC 132μM）。这是首次在 P. muellerianus 中描述 chebulanin。
P. muellerianus 的水醇提取物以及在基于生物活性的分级分离过程中获得的几个亚级分对 Hyal-1 表现出强烈的活性。主要活性与鞣花单宁 chebulanin 相关。此外，还观察到协同作用，表明使用 P. muellerianus 的水提取物而不是分离的单宁是合理的。植物作为抗炎剂用于改善伤口愈合的传统用途可以通过其成分的抗 Hyal-1 活性来合理化。
