Abstract：
BACKGROUND: Crocus sativus L. known as saffron, is a popular food condiment with a high aroma, deep colour, and long and thick threads (stigmas) cultivated in Iran, Morocco, Spain, Italy, China, Japan, France, Turkey, and India. In \'Ayurveda\', saffron is acknowledged for its immunostimulant, aphrodisiac, cardiotonic, liver tonic, nervine tonic, carminative, diaphoretic, diuretic, emmenagogue, galactagogue, febrifuge, sedative, relaxant, and anxiolytic activities. The renowned Persian physician and philosopher, Avicenna, delineated saffron as an antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilator, and aphrodisiac in his book, the Canon of Medicine. Within traditional Iranian Medicine (TIM), saffron is characterized as a mood elevator and a rejuvenator for the body and senses. Further, the ethnopharmacological evidence indicates that saffron has shown an effect against neurodegenerative disorders namely, dementia, Alzheimer\'s, and Parkinson\'s with its bioactive constituents i.e., carotenoids and apocarotenoids.
OBJECTIVE: The present study aimed to investigate the potential of standardized (Kashmir Saffron, India) Crocus sativus extract (CSE) in chronic scopolamine-induced cognitive impairment, amyloid beta (Aβ) plaque, and neurofibrillary tangles (NFT) accumulation in rat brains by targeting AChE inhibition and scopolamine mechanistic effect.
METHODS: The experimental animals were divided into six groups: group 1: normal control, group 2: scopolamine, group 3,4 and 5 rivastigmine tartrate, CSE (p.o. 10 mg/kg, 15 mg/kg, and 20 mg/kg) respectively. Each treatment group received scopolamine after 20 min of dosing, till 4 weeks. The effects of different treatments on learning, acquisition, and reversal memory were performed using a Morris water maze test. In addition to behavioral assessments, biochemical parameters such as AChE, IL-6, and antioxidants were measured in isolated brains. Histological observations were also conducted to assess the presence of Aβ plaques and NFT. Furthermore, molecular docking was performed to explore the potential AChE inhibitory activity of the bioactive constituents of standardized CSE.
RESULTS: Scopolamine produces memory impairment, and its chronic administration forms Aβ plaque and NFT in rat brains. Supplementation with CSE in presence of scopolamine has shown remarkable effects on behavioural activity, special acquisition, and reversal memory. The CSE has also shown promising effects on AChE inhibition and antioxidant activity. The results of the docking study also indicate that trans-crocetin, i.e., a biologically active metabolite of Crocins, has strong AChE inhibitory activity, supported by an in vivo animal experiment.
CONCLUSIONS: Supplementation with CSE significantly attenuates the formation of Aβ plaque and NFT in the hippocampus at a dose of 20 mg/kg per day. In addition, CSE also counters scopolamine-induced neuroinflammation.
OBJECTIVE: The present study aimed to investigate the potential of standardized (Kashmir Saffron, India) Crocus sativus extract (CSE) in chronic scopolamine-induced cognitive impairment, amyloid beta (Aβ) plaque, and neurofibrillary tangles (NFT) accumulation in rat brains by targeting AChE inhibition and scopolamine mechanistic effect.
METHODS: The experimental animals were divided into six groups: group 1: normal control, group 2: scopolamine, group 3,4 and 5 rivastigmine tartrate, CSE (p.o. 10 mg/kg, 15 mg/kg, and 20 mg/kg) respectively. Each treatment group received scopolamine after 20 min of dosing, till 4 weeks. The effects of different treatments on learning, acquisition, and reversal memory were performed using a Morris water maze test. In addition to behavioral assessments, biochemical parameters such as AChE, IL-6, and antioxidants were measured in isolated brains. Histological observations were also conducted to assess the presence of Aβ plaques and NFT. Furthermore, molecular docking was performed to explore the potential AChE inhibitory activity of the bioactive constituents of standardized CSE.
RESULTS: Scopolamine produces memory impairment, and its chronic administration forms Aβ plaque and NFT in rat brains. Supplementation with CSE in presence of scopolamine has shown remarkable effects on behavioural activity, special acquisition, and reversal memory. The CSE has also shown promising effects on AChE inhibition and antioxidant activity. The results of the docking study also indicate that trans-crocetin, i.e., a biologically active metabolite of Crocins, has strong AChE inhibitory activity, supported by an in vivo animal experiment.
CONCLUSIONS: Supplementation with CSE significantly attenuates the formation of Aβ plaque and NFT in the hippocampus at a dose of 20 mg/kg per day. In addition, CSE also counters scopolamine-induced neuroinflammation.
摘要：
背景：番红花被称为藏红花，是一种香气浓郁的食品调味品，深颜色,在伊朗种植的又长又粗的线(柱头)，摩洛哥,西班牙,意大利,中国,Japan,法国,土耳其,和印度。在\'阿育吠陀\'中，藏红花因其免疫刺激剂而被认可，壮阳药,强心剂,补肝,神经滋补品，驱风,发汗,利尿剂,煽动者，半乳糖,Febrifuge,镇静剂,松弛剂,和抗焦虑活动。著名的波斯医生和哲学家，Avicenna,将藏红花描述为抗抑郁药，催眠,抗炎,保肝,支气管扩张剂,和壮阳药在他的书中，医学的佳能在伊朗传统医学（TIM）中，藏红花的特点是情绪电梯和身体和感官的恢复。Further,民族药理学证据表明藏红花已经显示出对抗神经退行性疾病的作用，痴呆症,老年痴呆症,和帕金森及其生物活性成分，即，类胡萝卜素和载脂蛋白类胡萝卜素。
目的：本研究旨在调查标准化(克什米尔藏红花，印度）藏红花提取物（CSE）在慢性东pol碱引起的认知障碍中，淀粉样β（Aβ）斑块，和神经原纤维缠结（NFT）在大鼠大脑中的积累通过靶向AChE抑制和东莨菪碱的机制作用。
方法：实验动物分为6组：第1组：正常对照组，第2组:东pol碱,3、4和5组酒石酸利伐斯的明，CSE（p.o.10mg/kg，15mg/kg,和20mg/kg）。每个治疗组在20分钟后接受东莨菪碱。剂量，直到4周。不同治疗方法对学习的影响，收购,使用Morris水迷宫测试进行逆转记忆。除了行为评估，生化参数，如AChE，在分离的大脑中测量IL-6和抗氧化剂。还进行组织学观察以评估Aβ斑块和NFT的存在。此外，进行分子对接以探索标准化CSE的生物活性成分的潜在AChE抑制活性。
结果：东莨菪碱会导致记忆障碍，其慢性给药在大鼠大脑中形成Aβ斑块和NFT。在东pol碱存在的情况下补充CSE对行为活动显示出显着影响，特殊收购，和反转记忆。CSE还显示了对AChE抑制和抗氧化活性的有希望的效果。对接研究的结果还表明，反式藏红花酸，即，藏红花的生物活性代谢产物,具有较强的AChE抑制活性，由体内动物实验支持。
结论：在每天20mg/kg的剂量下，补充CSE可显着减弱海马中Aβ斑块和NFT的形成。此外,CSE还对抗东pol碱诱导的神经炎症。
目的：本研究旨在调查标准化(克什米尔藏红花，印度）藏红花提取物（CSE）在慢性东pol碱引起的认知障碍中，淀粉样β（Aβ）斑块，和神经原纤维缠结（NFT）在大鼠大脑中的积累通过靶向AChE抑制和东莨菪碱的机制作用。
方法：实验动物分为6组：第1组：正常对照组，第2组:东pol碱,3、4和5组酒石酸利伐斯的明，CSE（p.o.10mg/kg，15mg/kg,和20mg/kg）。每个治疗组在20分钟后接受东莨菪碱。剂量，直到4周。不同治疗方法对学习的影响，收购,使用Morris水迷宫测试进行逆转记忆。除了行为评估，生化参数，如AChE，在分离的大脑中测量IL-6和抗氧化剂。还进行组织学观察以评估Aβ斑块和NFT的存在。此外，进行分子对接以探索标准化CSE的生物活性成分的潜在AChE抑制活性。
结果：东莨菪碱会导致记忆障碍，其慢性给药在大鼠大脑中形成Aβ斑块和NFT。在东pol碱存在的情况下补充CSE对行为活动显示出显着影响，特殊收购，和反转记忆。CSE还显示了对AChE抑制和抗氧化活性的有希望的效果。对接研究的结果还表明，反式藏红花酸，即，藏红花的生物活性代谢产物,具有较强的AChE抑制活性，由体内动物实验支持。
结论：在每天20mg/kg的剂量下，补充CSE可显着减弱海马中Aβ斑块和NFT的形成。此外,CSE还对抗东pol碱诱导的神经炎症。
