Parul Institute of Pharmacy, Parul University, Vadodara, 391760, Gujarat, India.
Pharmanza Herbal Pvt. Ltd., Anand, 388430, Gujarat, India.
J Ethnopharmacol. 2024 May 23;326:117898. doi: 10.1016/j.jep.2024.117898. Epub 2024 Feb 8.
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.
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.
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.
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.
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.
藏红花，又称番红花，是一种流行的食用调味品，具有浓郁的香气、深沉的颜色和长而粗的线（柱头）。它在伊朗、摩洛哥、西班牙、意大利、中国、日本、法国、土耳其和印度等地种植。在“阿育吠陀”中，藏红花因其免疫刺激、壮阳、强心、肝滋补、神经滋补、化气、发汗、利尿、通经、催奶、退热、镇静、松弛和抗焦虑作用而受到认可。著名的波斯医生和哲学家阿维森纳在他的著作《医典》中描述藏红花为抗抑郁药、催眠药、消炎药、保肝药、支气管扩张药和壮阳药。在伊朗传统医学（TIM）中，藏红花被认为是一种能提升情绪的药物，能使身体和感官恢复活力。此外，民族药理学证据表明，藏红花对神经退行性疾病，如痴呆症、阿尔茨海默病和帕金森病有一定的治疗效果，其生物活性成分包括类胡萝卜素和脱甲叶黄素。
本研究旨在探讨标准化（印度克什米尔藏红花）藏红花提取物（CSE）通过抑制乙酰胆碱酯酶和阻断东莨菪碱的作用机制，对慢性东莨菪碱诱导的认知障碍、β-淀粉样蛋白（Aβ）斑块和神经纤维缠结（NFT）在大鼠大脑中的潜在作用。
实验动物分为六组：第 1 组：正常对照组；第 2 组：东莨菪碱组；第 3、4 和 5 组：分别给予柠檬酸他克林、CSE（口服 10mg/kg、15mg/kg 和 20mg/kg）。每组在给药 20 分钟后给予东莨菪碱，持续 4 周。使用 Morris 水迷宫测试评估不同治疗方法对学习、获得和反转记忆的影响。除行为评估外，还测量了分离大脑中的乙酰胆碱酯酶、白细胞介素 6 和抗氧化剂等生化参数。还进行了组织学观察，以评估 Aβ斑块和 NFT 的存在。此外，还进行了分子对接，以探索标准化 CSE 的生物活性成分对乙酰胆碱酯酶的潜在抑制活性。
东莨菪碱可导致记忆障碍，其慢性给药可在大鼠大脑中形成 Aβ斑块和 NFT。CSE 与东莨菪碱联合补充显示出对行为活动、特殊获得和反转记忆的显著作用。CSE 还显示出对乙酰胆碱酯酶抑制和抗氧化活性的良好效果。对接研究的结果还表明，反式藏红花素，即藏红花素的一种生物活性代谢物，具有很强的乙酰胆碱酯酶抑制活性，这一结果得到了体内动物实验的支持。
每天 20mg/kg 的 CSE 补充可显著减少海马中 Aβ斑块和 NFT 的形成。此外，CSE 还能对抗东莨菪碱引起的神经炎症。
