Ambamba Bruno Dupon Akamba, Paka Ghislain Djiokeng, Takuissu Guy Roussel Nguemto, Nongni Quentin Cicilien Piebeng, Ntepe Leonel Javeres Mbah, Ella Fils Armand, Mandob Damaris Enyegue, Fonkoua Martin, Ngondi Judith Laure
Department of Biochemistry, Faculty of Science, University of Yaounde 1, P.O. Box 812, Yaounde, Cameroon; Center of Nutrition and Functional Foods, Yaounde 8024, Cameroon.
Department of Biochemistry, Faculty of Science, University of Yaounde 1, P.O. Box 812, Yaounde, Cameroon.
Biomed Pharmacother. 2025 May;186:118010. doi: 10.1016/j.biopha.2025.118010. Epub 2025 Mar 31.
Alzheimer's disease (AD) is the most commonly diagnosed form of senile dementia, with limited therapeutic options. Neuronal damage is caused by factors secreted by inflammatory cells but also, the lack of antioxidants to prevent oxidative stress and help maintain neuronal integrity, which is crucial for cognition and memory are mediators of AD. Terminalia macroptera barks contain glycosyl terpenoids, known for their strong antioxidant properties. This study investigated the antioxidant and neuroprotective effects of the glycosylic terpenoid-rich fraction of Terminalia macroptera (GT-TeMac™) in scopolamine-treated rats.
Glycosylic terpenoids were identified by LC-MS and antiradical activity tests (DPPH and ORAC) were performed. Cholinergic cognitive dysfunction and oxidative stress were induced in male wistar rats, by intraperitoneal injection of scopolamine (1 mg/kg BW/day) for seven consecutive days. GT-TeMac™ at 100 mg/kg and Donepezil at 5 mg/kg body weight were administered orally 60 min after scopolamine. After treatment, rat were sacrificed and brains were collected for the evaluation of cholinergic enzyme activity, oxidative stress markers and histopathological analysis. In vitro study was carried out to assess the ability of GT-TeMac™ to scavenge free radicals and suppress HO-induced ROS production in SK-N-SH cells. In addition, the ability of GT-TeMac™ to restore cell viability reduced by acrolein was performed.
Chebuloside II, Sericoside, 24-deoxysericoside, arjunglucoside 1 and 23-galloylarjunolic acid 28-O-glucopyranosylester were identified by LC-MS. GT-TeMac™ has a SC of 9.54 μg/mL and an ORAC value of 1130 µM Trolox equivalent per mg of GT-TeMac™. The administration of GT-TeMac™ protected against cognitive decline in AD by inhibiting cholinesterase metabolism, modulating oxidative stress parameters and protecting hippocampal areas. Additionally, GT-TeMac™ absorbed and eliminated ROS produced by hydrogen peroxide in SKNSH cells and restored cell viability reduced by acrolein.
These findings suggest that the active ingredients in GT-TeMac™ are promising drug candidates for the treatment of cognitive disorders associated with oxidative stress in AD.
阿尔茨海默病（AD）是最常见的老年性痴呆形式，治疗选择有限。神经元损伤是由炎症细胞分泌的因子引起的，而且缺乏抗氧化剂来预防氧化应激并帮助维持神经元完整性，而这对认知和记忆至关重要，是AD的介导因素。大翅榄仁树皮含有糖基萜类化合物，以其强大的抗氧化特性而闻名。本研究调查了大翅榄仁富含糖基萜类化合物的部分（GT-TeMac™）对东莨菪碱处理的大鼠的抗氧化和神经保护作用。
通过液相色谱-质谱联用（LC-MS）鉴定糖基萜类化合物，并进行抗自由基活性测试（DPPH和ORAC）。通过连续7天腹腔注射东莨菪碱（1mg/kg体重/天）诱导雄性Wistar大鼠出现胆碱能认知功能障碍和氧化应激。在注射东莨菪碱60分钟后，分别口服给予100mg/kg的GT-TeMac™和5mg/kg体重的多奈哌齐。治疗后，处死大鼠并收集大脑，以评估胆碱能酶活性、氧化应激标志物和进行组织病理学分析。进行体外研究以评估GT-TeMac™清除自由基和抑制SK-N-SH细胞中过氧化氢诱导的活性氧（ROS）产生的能力。此外，还检测了GT-TeMac™恢复由丙烯醛降低的细胞活力的能力。
通过LC-MS鉴定出诃子苷II、丝胶苷、24-脱氧丝胶苷、arjunglucoside 1和23-没食子酰arjunolic酸28-O-吡喃葡萄糖苷酯。GT-TeMac™的半抑制浓度（SC）为9.54μg/mL，每毫克GT-TeMac™的氧自由基吸收能力（ORAC）值为1130μM Trolox当量。给予GT-TeMac™可通过抑制胆碱酯酶代谢、调节氧化应激参数和保护海马区来预防AD中的认知衰退。此外，GT-TeMac™吸收并清除了SKNSH细胞中过氧化氢产生的ROS，并恢复了由丙烯醛降低的细胞活力。
这些发现表明，GT-TeMac™中的活性成分有望成为治疗与AD中氧化应激相关的认知障碍的候选药物。
