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(豆科)水提取物通过引发活性氧依赖的氧化损伤并抑制乙酰胆碱酯酶、γ-氨基丁酸转氨酶和单胺氧化酶A来预防与更年期相关的神经精神疾病:,,和方法。

(Fabaceae) aqueous extract to prevent neuropsychiatric disorders associated with menopause by triggering ROS-dependent oxidative damage and inhibiting acetylcholinesterase, GABA-transaminase, and monoamine oxidase A: , , and approaches.

作者信息

Owona Pascal Emmanuel, Mengue Ngadena Yolande Sandrine, Bilanda Danielle Claude, Ngoungouré Madeleine Chantal, Mbolang Nguegan Lohik, Bidingha A Goufani Ronald, Kahou Tadah Rivaldo Bernes, Noubom Michel, Ella Armand Fils, Tcheutchoua Yannick Carlos, Ambamba Akamba Bruno Dupon, Bouguem Yandja Paule Cynthia, Keumedjio Teko Paulin, Dzeufiet Djomeni Paul Desire, Kamtchouing Pierre

机构信息

Department of Animal Biology and Physiology, Laboratory of Animal Physiology, Faculty of Science, University of Yaoundé 1, P.O. Box 812 Yaoundé, Cameroon.

Neurosciences and psychogerontology axis, Laboratory of Development and Maldevelopment, Department of Psychology, Faculty of Arts, Letters, and Social Science, University of Yaoundé 1, P.O. Box. 755 Yaoundé, Cameroon.

出版信息

Heliyon. 2024 Jun 28;10(13):e33843. doi: 10.1016/j.heliyon.2024.e33843. eCollection 2024 Jul 15.

Abstract

(PS) is traditionally used in Cameroon medicine to alleviate postmenopausal symptoms. Previous research has shown that it has tissue-selective potential and estrogen-mimetic effects on vaginal atrophy. Phytoestrogens like 7--acetyl formononetin, khrinone A, and 3',5'-dimethoxy-4-stilbenol were found in its water extract by UHPLC, but there is no evidence of its effects on neurological disorders linked to post-menopause (ND-PO). The study aimed to investigate the phytochemical profile of PS aqueous extract, assess its neuroprotective potential in rats, and explore possible underlying pathways. We used colorimetric assays to study the phytochemical profile of PS extract. Effects of the extract on behavioral parameters, neuronal signaling, and integrity in an 84-day ovariectomized rat model. Molecular docking was performed to assess the ability of 7--acetyl formononetin, an isoflavone contained in PS, to cross the BBB and its binding affinity to the active sites of AChE, MAO-A, and GABA-T. Besides, the anti-AChE/BChE, antioxidant, and anti-inflammatory effects of PS were assessed by tests. PS aqueous extract contains polyphenols (656.58 ± 9.18 mgEAG/100gMS), flavonoids (201.25 ± 5.52 mgEQ/100gDW), and tannins (18.42 ± 1.25 mg/100gDW). It slows down anxiety, depressive disorders, cellular disorganization, and neuronal death in the hippocampus, dentate gyrus, and neocortex. modeling was a powerful tool to assess the 7--acetylformononetin's ability to cross the BBB and strongly bind and inhibit AChE, MAO-A, and GABA-T. Thus, by combining GABAergic, cholinergic, and serotoninergic modulation, PS aqueous extract also possesses remarkable anti-AChE/BChE and induces antioxidant and anti-inflammatory potential in macrophages. Such estromimetics, antioxidant, anti-inflammatory, cholinergic, and monoaminergic modulators represent promising activities to develop neuroprotective drugs with optimal therapeutic profiles for menopausal women.

摘要

(PS)传统上用于喀麦隆医学以缓解绝经后症状。先前的研究表明,它具有组织选择性潜力以及对阴道萎缩的雌激素模拟作用。通过超高效液相色谱法(UHPLC)在其水提取物中发现了植物雌激素,如7 - 乙酰基大豆黄素、khrinone A和3',5'-二甲氧基-4-芪醇,但没有证据表明其对与绝经后相关的神经障碍(ND-PO)有影响。该研究旨在调查PS水提取物的植物化学特征,评估其在大鼠中的神经保护潜力,并探索可能的潜在途径。我们使用比色法研究PS提取物的植物化学特征。在一个84天的去卵巢大鼠模型中研究提取物对行为参数、神经元信号传导和完整性的影响。进行分子对接以评估PS中含有的异黄酮7 - 乙酰基大豆黄素穿过血脑屏障的能力及其与乙酰胆碱酯酶(AChE)、单胺氧化酶A(MAO-A)和γ-氨基丁酸转氨酶(GABA-T)活性位点的结合亲和力。此外,通过测试评估PS的抗AChE/BChE、抗氧化和抗炎作用。PS水提取物含有多酚(656.58 ± 9.18 mgEAG/100gMS)、黄酮类化合物(201.25 ± 5.52 mgEQ/100gDW)和单宁(18.42 ± 1.25 mg/100gDW)。它减缓了海马体、齿状回和新皮质中的焦虑、抑郁障碍、细胞紊乱和神经元死亡。分子对接是评估7 - 乙酰基大豆黄素穿过血脑屏障并强烈结合和抑制AChE、MAO-A和GABA-T能力的有力工具。因此,通过结合γ-氨基丁酸能、胆碱能和5-羟色胺能调节,PS水提取物还具有显著的抗AChE/BChE作用,并在巨噬细胞中诱导抗氧化和抗炎潜力。这种雌激素模拟物、抗氧化剂、抗炎剂、胆碱能和单胺能调节剂代表了开发具有最佳治疗特性用于绝经后女性的神经保护药物的有前景的活性成分。

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