Department of Biological Sciences, Faculty of Science, University of Maroua, P.O. Box 814, Maroua, Cameroon.
Centre for Natural Product Research, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa.
J Ethnopharmacol. 2023 Jun 12;309:116325. doi: 10.1016/j.jep.2023.116325. Epub 2023 Mar 9.
Dementias including Alzheimer disease (AD) are three times higher in menopausal women than in men. Phytoestrogens, a group of plant-derived compounds are known to alleviate menopausal complaints including dementia. Millettia griffoniana Baill is a phytoestrogen-rich plant used to treat menopausal complaints and dementia.
Evaluating the estrogenic and neuroprotective potential of Millettia griffoniana on ovariectomized (OVX) rats.
The in vitro safety of M. griffoniana ethanolic extract was assayed by MTT in human mammary epithelial (HMEC) and mouse neuronal (HT-22) cells and its lethal dose 50 (LD) was estimated following OECD 423 guidelines. For estrogenicity, in vitro the well known E-screen assay on MCF-7 cells was performed and in vivo four groups of OVX rats were treated either with 75, 150 and 300 mg/kg M. griffoniana extract doses or estradiol (1 mg/kg BW) for three days; and changes in uterine and vagina were analyzed. Then, for neuroprotective effect, Alzheimer-type dementia induction was achieved by scopolamine (1.5 mg/kg B.W., i.p.) injection four days/week and M. griffoniana extract as well as piracetam (standard) were administered daily for 2 weeks to evaluate the extract's neuroprotective potential. The endpoints were the assessment of learning and working memory, oxidative stress state (SOD, CAT, and MDA) in brain, acetylcholine esterase (AChE) activity and the histopathological changes in hippocampus.
No toxic effect was observed when incubating mammary (HMEC) and neuronal (HT-22) cells with M. griffoniana ethanol extract for 24 h and its LD was found >2000 mg/kg. The extract also exhibited both in vitro and in vivo estrogenic activities, displayed by a significant (p < 0.01) increment in MCF-7 cells population in vitro and an increase in the epithelium height of the vagina and the wet weight of the uterus mainly with the 150 mg/kg BW extract dose compared to untreated OVX rats. The extract also reversed scopolamine-induced memory impairment in rat by improving learning, working and reference memory. This was associated with an increment in CAT and SOD expression, alongside a decrement in MDA content and AChE activity in hippocampus. Further, the extract reduced neuronal cell loss in hippocampal structures (CA1, CA3 and dentate gyrus). High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) spectra, revealed the presence of numerous phytoestrogens in M. griffoniana extract.
M. griffoniana ethanolic extract has estrogenic, anticholinesterase and antioxidant activities that could account for its anti-amnesic effects. These findings therefore sheds light on why this plant is commonly used in the therapy of menopausal complaints and dementia.
与男性相比，更年期女性患痴呆症（包括阿尔茨海默病）的风险高 3 倍。植物雌激素是一组植物来源的化合物，已知可缓解更年期症状，包括痴呆症。密花豆是一种富含植物雌激素的植物，用于治疗更年期症状和痴呆症。
评估密花豆对去卵巢（OVX）大鼠的雌激素和神经保护作用。
采用 MTT 法检测密花豆乙醇提取物对人乳腺上皮（HMEC）和小鼠神经元（HT-22）细胞的体外安全性，并按照 OECD 423 指南估算其半数致死量（LD）。对于雌激素活性，在体外进行了已知的 MCF-7 细胞 E-screen 测定，在体内，将 4 组 OVX 大鼠分别用 75、150 和 300 mg/kg 密花豆提取物剂量或雌二醇（1mg/kg BW）处理 3 天；并分析子宫和阴道的变化。然后，为了评估神经保护作用，通过 scopolamine（1.5mg/kg BW，ip）注射每周 4 天诱导阿尔茨海默病样痴呆，并每天给予密花豆提取物和吡拉西坦（标准）治疗 2 周，以评估提取物的神经保护作用。终点是评估学习和工作记忆、大脑中的氧化应激状态（SOD、CAT 和 MDA）、乙酰胆碱酯酶（AChE）活性以及海马的组织病理学变化。
密花豆乙醇提取物在孵育乳腺（HMEC）和神经元（HT-22）细胞 24 小时内无毒性作用，其 LD 大于 2000mg/kg。该提取物还表现出体外和体内的雌激素活性，通过体外 MCF-7 细胞群体的显著增加（p<0.01）和未处理的 OVX 大鼠阴道上皮高度和子宫湿重的增加来显示，主要是用 150mg/kg BW 提取物剂量。该提取物还通过改善学习、工作和参考记忆来逆转东莨菪碱诱导的记忆障碍。这与海马中 CAT 和 SOD 表达的增加以及 MDA 含量和 AChE 活性的降低有关。此外，该提取物减少了海马结构（CA1、CA3 和齿状回）中的神经元细胞丢失。高效液相色谱-质谱联用（HPLC-MS）图谱显示，密花豆提取物中存在多种植物雌激素。
密花豆乙醇提取物具有雌激素、乙酰胆碱酯酶抑制和抗氧化活性，这可以解释其抗健忘作用。这些发现因此阐明了为什么这种植物常用于治疗更年期症状和痴呆症。
