Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Sino-Africa Joint Research Center, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, 430074, China.
Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Sino-Africa Joint Research Center, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, 430074, China; Laboratory of Advanced Theranostic Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315300, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
J Ethnopharmacol. 2024 Oct 5;332:118356. doi: 10.1016/j.jep.2024.118356. Epub 2024 May 17.
Parasitic infections impose a significant burden on public health worldwide. European pharmacopoeia records and ethnopharmacological studies indicate that Hagenia abyssinica (Bruce) J.F. Gmel. has traditionally been used to treat a variety of parasitic infections, while the potential antiparasitic compounds remain ambiguous.
Acetylcholinesterase (AChE), lactate dehydrogenases (LDH), and glutathione reductase (GR) are the key target enzymes in the survival of parasites. The aim of our work was to screen antiparasitic compounds targeting AChE, LDH, and GR from H. abyssinica.
Ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS) combined with molecular docking was used in this study. Therein, the alamarBlue® and Ellman's methods were employed to reveal the antitrypanosomal effect and AChE inhibitory activity. Meanwhile, the UF-LC-MS was carried out to screen the potential active compounds from H. abyssinica. Subsequently, molecular docking was performed to evaluate the binding mechanisms of these active compounds with AChE, LDH, and GR. Finally, the AChE inhibitory activity of potential inhibitors was detected in vitro.
H. abyssinica exhibited significant antitrypanosomal and AChE inhibitory activity. Corilagin, brevifolin carboxylic acid, brevifolin, quercetin, and methyl ellagic acid were recognized as potential AChE inhibitors by UF-LC-MS, while methyl brevifolin carboxylate was identified as AChE, LDH, and GR multi-target inhibitor, with binding degree ranged from 20.96% to 49.81%. Molecular docking showed that these potential inhibitors had a strong affinity with AChE, LDH, and GR, with binding energies ranging from -6.98 to -9.67 kcal/mol. These findings were further supported by the observation that corilagin, quercetin, brevifolin carboxylic acid, and methyl brevifolin carboxylate displayed significant AChE inhibitory activity compared with the positive control (gossypol, 0.42 ± 0.04 mM), with IC values of 0.15 ± 0.05, 0.56 ± 0.03, 0.99 ± 0.01, and 1.02 ± 0.03 mM, respectively.
This study confirms the antiparasitic potential of H. abyssinica, supporting the traditional use of H. abyssinica in local ethnopharmacology to treat parasites. At the same time, corilagin, brevifolin carboxylic acid, brevifolin, quercetin, methyl ellagic acid, and methyl brevifolin carboxylate exert their anti-parasitic effects by inhibiting AChE, LDH, and GR, and they are expected to be natural lead compounds for the treatment of parasitic diseases.
寄生虫感染在全球范围内给公共卫生带来了重大负担。欧洲药典记载和民族药理学研究表明，Hagenia abyssinica（Bruce）J.F. Gmel. 传统上被用于治疗各种寄生虫感染，而潜在的抗寄生虫化合物仍不明确。
乙酰胆碱酯酶（AChE）、乳酸脱氢酶（LDH）和谷胱甘肽还原酶（GR）是寄生虫生存的关键靶酶。我们的工作旨在从 H. abyssinica 中筛选针对 AChE、LDH 和 GR 的抗寄生虫化合物。
本研究采用超滤-液相色谱-质谱联用（UF-LC-MS）结合分子对接。其中，alamarBlue® 和 Ellman's 方法用于揭示抗锥虫作用和 AChE 抑制活性。同时，进行 UF-LC-MS 以筛选来自 H. abyssinica 的潜在活性化合物。随后，进行分子对接以评估这些活性化合物与 AChE、LDH 和 GR 的结合机制。最后，在体外检测潜在抑制剂的 AChE 抑制活性。
H. abyssinica 表现出显著的抗锥虫和 AChE 抑制活性。通过 UF-LC-MS 鉴定出根皮苷、短叶苏木酚酸、短叶苏木酚、槲皮素和甲基鞣花酸为潜在的 AChE 抑制剂，而甲基短叶苏木酚酸被鉴定为 AChE、LDH 和 GR 的多靶标抑制剂，结合度为 20.96%至 49.81%。分子对接表明，这些潜在的抑制剂与 AChE、LDH 和 GR 具有很强的亲和力，结合能为-6.98 至-9.67 kcal/mol。这些发现得到了进一步支持，因为与阳性对照（棉酚，0.42±0.04 mM）相比，根皮苷、槲皮素、短叶苏木酚酸和甲基短叶苏木酚酸表现出显著的 AChE 抑制活性，IC 值分别为 0.15±0.05、0.56±0.03、0.99±0.01 和 1.02±0.03 mM。
本研究证实了 H. abyssinica 的抗寄生虫潜力，支持了 H. abyssinica 在当地民族药理学中用于治疗寄生虫的传统用途。同时，根皮苷、短叶苏木酚酸、短叶苏木酚、槲皮素、甲基鞣花酸和甲基短叶苏木酚酸通过抑制 AChE、LDH 和 GR 发挥其抗寄生虫作用，有望成为治疗寄生虫病的天然先导化合物。
