开发用于治疗阿尔茨海默病 (AD) 的天然草药药物，需要识别和验证能够靶向该疾病复杂病理机制（包括炎症、氧化应激和淀粉样蛋白沉积）的生物活性植物化合物。由于需要进行严格的临床试验并克服生物利用度低等问题，这一过程极具挑战性。
当前研究现状 针对 AD 的天然产物研究是一个蓬勃发展的领域，通常借鉴传统医学体系。虽然目前尚无任何草药获得 FDA 批准用于治疗或预防 AD，但一些植物来源的化合物在临床前研究和小规模人体研究中显示出良好的前景。
主要研究领域包括：
乙酰胆碱酯酶 (AChE) 抑制：许多有前景的草药含有能够抑制 AChE 的化合物。AChE 是一种分解神经递质乙酰胆碱的酶，而乙酰胆碱对记忆和认知功能至关重要。这与一些经FDA批准的阿尔茨海默病处方药的作用机制类似，例如从水仙花球茎中提取的加兰他敏。 抗炎和抗氧化作用：阿尔茨海默病的发病机制涉及慢性神经炎症和氧化应激，许多植物化合物具有强大的抗氧化和抗炎特性，可能减轻神经元损伤。 β-淀粉样蛋白 (Aβ) 和 tau 蛋白调节：一些天然化合物似乎可以抑制 Aβ 斑块和神经原纤维缠结（tau 蛋白聚集体）的形成并促进其清除，而 Aβ 斑块和神经原纤维缠结是阿尔茨海默病在大脑中的典型标志。 有前景的草药候选药物 目前正在研究几种草药和天然化合物在控制阿尔茨海默病症状和延缓疾病进展方面的潜力：
银杏：因其增强血液流动和为大脑提供抗氧化保护的能力而得到广泛研究。大规模临床试验，例如“银杏记忆评估（GEM）研究”，在预防或延缓阿尔茨海默病方面取得了喜忧参半的结果，但一些较小的研究表明，银杏在控制现有症状方面有一定益处。
石杉碱甲：一种从石杉（Huperzia serrata）中提取的生物碱，属于乙酰胆碱酯酶抑制剂，常作为非处方保健品使用。一些研究表明其有效，但美国的大型临床试验并未发现其疗效显著优于安慰剂。
姜黄素：姜黄（Curcuma longa）中的活性成分，具有强大的抗炎和抗氧化特性，目前正在研究其减少淀粉样蛋白沉积的能力。其主要挑战是生物利用度低（难以被人体和大脑吸收）。
假马齿苋：在阿育吠陀医学中用于增强记忆力，其含有假马齿苋苷，可改善神经冲动传递并防止氧化损伤。小型临床试验表明，假马齿苋可以改善记忆力和注意力。
鼠尾草：研究表明，鼠尾草可通过增强胆碱能活性，改善轻度至中度阿尔茨海默病患者的认知能力并减轻其躁动。
藏红花（番红花）：藏红花提取物在治疗轻度至中度阿尔茨海默病症状方面，疗效与传统阿尔茨海默病药物多奈哌齐相当，且在一些研究中副作用更少。
开发药用级草药面临诸多挑战： 标准化：草药提取物的化学成分天然存在差异，难以实现标准化剂量和稳定的产品质量。 生物利用度：许多植物来源的化合物难以穿过血脑屏障（BBB）达到脑内治疗浓度。
临床验证：需要进行严格、大规模和长期的临床试验，以满足监管要求（例如美国食品药品监督管理局 (FDA) 的要求），从而确认其疗效和安全性。
药物相互作用：草药补充剂可能与处方药发生相互作用，这给通常服用多种药物的患者带来安全隐患。 研究人员正在致力于开发先进的递送方法，例如基于纳米技术的载体，以提高天然化合物的生物利用度并实现其向大脑的靶向递送。包括阿尔茨海默病协会在内的科学界普遍认为，还需要开展更多研究，患者在使用任何补充剂之前都应咨询医生。
Research into natural products for AD is a growing field, often drawing on traditional medicine systems. While no herbal drugs are currently approved by the FDA for the treatment or prevention of AD, several plant-derived compounds show promise in preclinical and small-scale human studies.
Key areas of research focus on:
Acetylcholinesterase (AChE) inhibition: Many promising herbs contain compounds that inhibit AChE, an enzyme that breaks down the neurotransmitter acetylcholine, which is crucial for memory and cognitive function. This is similar to the mechanism of action of some FDA-approved prescription drugs for AD, such as galantamine, which is derived from the daffodil bulb plant.
- Anti-inflammatory and antioxidant effects: AD pathogenesis involves chronic neuroinflammation and oxidative stress, and many plant compounds possess potent antioxidant and anti-inflammatory properties that may mitigate neuronal damage.
- Amyloid-beta (Aβ) and tau protein modulation: Some natural compounds appear to inhibit the formation and promote the clearance of Aβ plaques and neurofibrillary tangles (tau protein aggregates), the characteristic hallmarks of AD in the brain.
Promising Herbal Candidates
Several herbs and natural compounds are being investigated for their potential in managing AD symptoms and progression:
- Ginkgo biloba: Extensively studied for its ability to enhance blood flow and provide antioxidant protection to the brain. Large-scale clinical trials, such as the ” Ginkgo Evaluation of Memory (GEM) ” Study, have yielded mixed results regarding its efficacy in preventing or delaying AD, but some smaller studies suggest a modest benefit in managing existing symptoms.
- Huperzine A: An alkaloid derived from the Chinese club moss (Huperzia serrata), it is an AChE inhibitor and is used as an over-the-counter supplement. It has demonstrated effectiveness in some studies, although large U.S. clinical trials have found no significant benefit over a placebo.
- Curcumin: The active compound in turmeric (Curcuma longa), it has potent anti-inflammatory and antioxidant properties and is being explored for its ability to reduce amyloid accumulation. Its primary challenge is low bioavailability (poor absorption into the body and brain).
- Bacopa monnieri: Used in Ayurvedic medicine for memory enhancement, it contains bacosides that improve nerve impulse transmission and protect against oxidative damage. Small clinical trials suggest improvements in memory and attention.
- Salvia officinalis (Sage): Studies have shown that sage can improve cognitive performance and reduce agitation in patients with mild-to-moderate AD by enhancing cholinergic activity.
- Saffron (Crocus sativus): Saffron extract has shown comparable efficacy to the conventional AD drug donepezil in treating mild-to-moderate AD symptoms, with fewer side effects in some studies.
Challenges in Development
Developing a pharmaceutical-grade herbal drug involves significant hurdles:
- Standardization: Herbal extracts naturally vary in chemical composition, making standardized dosing and consistent product quality difficult to achieve.
- Bioavailability: Many plant-derived compounds face challenges crossing the blood-brain barrier (BBB) to reach therapeutic concentrations in the brain.
- Clinical Validation: Rigorous, large-scale, and long-term clinical trials are needed to meet regulatory requirements (like those of the FDA) to confirm efficacy and safety.
- Drug Interactions: Herbal supplements can interact with prescription medications, raising safety concerns for patients often on multiple drugs.
- Researchers are working on advanced delivery methods, such as nanotechnology-based carriers, to enhance the bioavailability and targeted delivery of natural compounds to the brain. The general consensus in the scientific community, including the Alzheimer’s Association, is that more research is needed, and patients should consult a physician before using any supplements.
(UC Chinese Press, San Diego Chinese Press, Report by Ranxin Shi, Xiuli Zhao, Yuhan Shi, Editor: Fei Lu)
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根据美国药学院协会（AACP）最近公布的数据，加州大学圣地亚哥分校斯卡格斯药学院和药物科学学院(（Skaggs School of Pharmacy and Pharmaceutical Sciences，简称UC San Diego SSPPS）在全国研究经费排名中较去年上升三位，位列第四。
在2023-2024财年里，UC San Diego SSPPS 从包括美国国家儿童健康与人类发育研究所、美国国家老龄研究所和美国国家心肺血液研究所等机构获得了约3300万美元的竞争性科研经费。
“在如今的联邦资助竞争激烈的环境下，每一分钱都来之不易——然而，我们的教职员工依然保持着最高水平的竞争力，”加州大学圣地亚哥分校医学院临床药学和儿科学教授、斯卡格斯药学院院长兼药学博士、应用科学硕士 Brookie Best表示。“我们这里开展的杰出科研工作正在对儿童健康、神经退行性疾病、心力衰竭、微生物组等领域产生切实的影响。但我们不能将这种支持视为理所当然，如果没有联邦层面的持续投入，像这样具有变革意义的研究将面临风险。我要祝贺我们规模虽小但成果丰硕的教职员工，他们获得了这些奖项，使我们在药学研究领域跻身全国领先行列。”
美国药学院协会 (AACP) 每年发布的这份报告汇总了美国各药学院获得的校外科研经费总额。排名依据公共数据库，例如美国国立卫生研究院 (NIH) 的 RePORT 数据库，并通过与各院校合作进行核实，以确保数据的准确性。
“我们的研究范围非常广泛，”斯克里普斯药学院和药学科学学院负责研究与创新的副院长、加州大学圣地亚哥分校医学院儿科学教授 Elizabeth Winzeler博士说，“这些资助不仅是对我们科研质量的认可，也是对我们教职员工创造力和决心的肯定。我为他们的工作获得全国认可而感到自豪。”
推动药学院科研实力的主要资助项目
· 研究母乳喂养期间抗生素的传播
药学博士Shirley Tsunoda是临床药学教授兼药学教育副院长，也是尤尼斯·肯尼迪·施莱佛国家儿童健康与人类发育研究所一项资助项目的首席研究员之一。该项目旨在支持母婴精准药理学卓越中心，角田博士及其团队在该中心领导开展研究，以确定母乳喂养期间服用抗生素是否会改变婴儿的微生物群。这个问题对儿童的长期健康具有重大意义。
· 研发治疗阿尔茨海默病及相关疾病的新药
药学教授Conor Caffrey博士是美国国家老龄研究所资助的一项旨在开发阿尔茨海默病和其他tau蛋白相关神经退行性疾病新疗法的项目负责人。该项目负责人、药学教授Carlo Bellatore博士不幸去世后，Caffrey博士及其团队正继续推进这项研究，探索一种名为CNDR-51997的新型化合物，该化合物能够稳定大脑的微管系统——微管系统是维持神经元健康功能的关键结构。在联邦政府的支持下，该团队正致力于推进该化合物进入人体临床试验阶段。
· 心肌损伤后的再生
药学教授、博士Sylvia Evans是这项由美国国家心肺血液研究所资助的项目的负责人，该项目专注于损伤后心肌的再生。与鱼类或两栖动物不同，人类心脏无法自然替换丢失的肌肉细胞，这也是心力衰竭仍然是全球首要死因的原因。埃文斯的研究旨在找出阻止人类心肌细胞分裂的遗传和代谢“障碍”，并设计克服这些障碍的策略。其长期目标是为再生疗法铺平道路，使受损的心脏有朝一日能够自我修复。
· 构建全球最大的微生物组化学库
药学教授、博士Pieter Dorrenstein获得了美国国家糖尿病、消化和肾脏疾病研究所的资助，用于构建有史以来规模最大的微生物组衍生化学物质参考库——最多可包含五百万个分子。我们肠道中的微生物会产生无数影响人类健康的化学物质，但其中大多数尚未被发现。多伦斯坦的团队将采用一种创新的“反向代谢组学”方法，将这些化学物质与食物、疾病和健康结果联系起来。目前，该团队已经发现了与克罗恩病相关的新的胆汁酸分子。由此建立的公共数据库将加速精准营养、诊断和新疗法的研究。
提供3300万美元竞争性研究奖励的资助机构包括美国国立儿童健康与人类发展研究所（National Institute of Child Health and Human Development）、国家老龄化研究所（National Institute on Aging）和国家心肺血液研究所（National Heart, Lung, and Blood Institute）等“大佬”机构。
According to recent data released by the Association of American Colleges of Pharmacy (AACP), the Skaggs School of Pharmacy and Pharmaceutical Sciences (UC San Diego SSPPS) at the University of California, San Diego, rose three places to rank fourth in national research funding rankings compared to last year.
In fiscal year 2023-2024, UC San Diego SSPPS received approximately $33 million in competitive research funding from institutions including the National Institute of Child Health and Human Development, the National Institute on Aging, and the National Heart, Lung, and Blood Institute.
“In today’s highly competitive federal funding environment, every penny is hard-earned—yet our faculty remains highly competitive,” said Brookie Best, Professor of Clinical Pharmacy and Pediatrics at the University of California, San Diego School of Medicine, Dean of the Skaggs School of Pharmacy, MD, PhD, and Master of Applied Science. “The outstanding research we are conducting here is having a real impact on areas such as children’s health, neurodegenerative diseases, heart failure, and the microbiome. But we cannot take this support for granted; without continued federal investment, transformative research like this would be at risk. I congratulate our small but accomplished faculty who have received these awards, placing us among the nation’s leaders in pharmaceutical research.”
This annual report, published by the Association of American Colleges of Pharmacy (AACP), summarizes the total amount of external research funding received by pharmacy schools across the United States. The rankings are based on public databases, such as the National Institutes of Health’s (NIH) RePORT database, and are verified in collaboration with various institutions to ensure data accuracy.
“Our research is very broad,” said Dr. Elizabeth Winzeler, Associate Dean for Research and Innovation at the Scripps School of Pharmacy and the School of Pharmaceutical Sciences, and Professor of Pediatrics at the University of California, San Diego School of Medicine. “These grants are not only recognition of the quality of our research, but also an affirmation of the creativity and determination of our faculty. I am proud that their work has received national recognition.”
Major funding projects to promote the research capabilities of the School of Pharmacy
• Study the transmission of antibiotics during breastfeeding
Shirley Tsunoda, PhD, is a Professor of Clinical Pharmacy and Associate Dean of Pharmacy Education, and one of the principal investigators for a funded project at the Eunice-Kennedy-Shreff National Institute of Child Health and Human Development. This project supports the Center of Excellence in Maternal and Infant Precision Pharmacology, where Dr. Tsunoda and her team are leading research to determine whether antibiotic use during breastfeeding alters the infant’s microbiome. This question has significant implications for children’s long-term health.
• Develop new drugs for the treatment of Alzheimer’s disease and related diseases
Dr. Conor Caffrey, a professor of pharmacy, was the principal investigator of a project funded by the National Institute on Aging aimed at developing new therapies for Alzheimer’s disease and other tau protein-related neurodegenerative diseases. Following the unfortunate passing of Dr. Carlo Bellatore, the project’s principal investigator and a professor of pharmacy, Dr. Caffrey and his team are continuing their research, exploring a novel compound called CNDR-51997, which can stabilize the brain’s microtubule system—a key structure for maintaining healthy neuronal function. With federal government support, the team is working to advance this compound into human clinical trials.
• Regeneration after myocardial injury
Sylvia Evans, a professor of pharmacy, is leading this project, funded by the National Heart, Lung, and Blood Institute, which focuses on the regeneration of damaged heart muscle. Unlike fish or amphibians, the human heart cannot naturally replace lost muscle cells, which is why heart failure remains the leading cause of death worldwide. Evans’ research aims to identify the genetic and metabolic “barriers” that prevent human heart muscle cell division and to design strategies to overcome these barriers. Her long-term goal is to pave the way for regenerative therapies that could one day enable damaged hearts to repair themselves.
• Construct the world’s largest microbiome chemical library
Pharmacy professor Pieter Dorrenstein has received funding from the National Institute of Diabetes, Digestive and Kidney Diseases to build the largest reference library of microbiome-derived chemicals ever created—containing up to five million molecules. The microbes in our gut produce countless chemicals that affect human health, but most of them remain undiscovered. Dorrenstein’s team will use an innovative “reverse metabolomics” approach to link these chemicals to food, disease, and health outcomes. The team has already discovered a new bile acid molecule associated with Crohn’s disease. The resulting public database will accelerate research into precision nutrition, diagnostics, and new therapies.
The funding agencies providing the $33 million competitive research awards include leading institutions such as the National Institute of Child Health and Human Development, the National Institute on Aging, and the National Heart, Lung, and Blood Institute.
(UC Chinese Press, San Diego Chinese Press, Report by Ranxin Shi, Xiuli Zhao, Yuhan Shi, Editor: Fei Lu)