Shiotani Mana, Hyohdoh Yuki, Hatakeyama Yutaka, Kazui Hiroaki, Okuhara Yoshiyasu
Center for Innovative and Translational Medicine, Kochi Medical School, Kochi University, Kohasu, Oko-Cho, Nankoku-Shi, Kochi, 783-8505, Japan.
Japanese Red Cross Kochi Hospital, 1-4-63-11 Hadaminamimachi, Kochi-Shi, Kochi, 780-8562, Japan.
BMC Geriatr. 2025 May 9;25(1):321. doi: 10.1186/s12877-025-05982-x.
In addition to conventional symptomatic treatment drugs, anti-amyloid beta antibody drugs are expected to benefit patients with Alzheimer's disease (AD). However, issues such as side effects and high costs persist, and new preventive and therapeutic drugs are desired. Meanwhile, information on the diagnosis and symptomatic treatment of AD accumulated during daily clinical practice is stored as real-world data and is considered a powerful means of discovering unknown factors that could provide clues for new prevention and treatment approaches for AD through comprehensive exploration.
We used anonymized hospital information system data from a tertiary care and academic hospital in Japan, spanning from 1981 to 2016, to search for potential suppressive factors for AD onset and to verify the validity of the discovered factors. We initially conducted a comprehensive search for candidate suppressive factors for AD and verified them using the inverse probability weighting (IPW) method with propensity scores.
From the comprehensive search, we identified glycyrrhizic acid (GA), a component of licorice, a traditional medicine with anti-inflammatory, antioxidant, antibacterial, and antiaging properties, as a candidate suppressing factor for AD. The IPW method showed that the odds ratio of developing AD in the GA group was 0.642 (95% confidence interval: 0.566-0.727) compared with the non-GA group after adjustment.
This is the first human study to suggest that GA may be a factor that can suppress the onset of AD. Additionally, our method could be a promising tool for drug repositioning that applies existing drugs already used in clinical settings with well-known side effects to diseases different from their original use.
除了传统的对症治疗药物外,抗淀粉样β抗体药物有望使阿尔茨海默病(AD)患者受益。然而,副作用和高成本等问题依然存在,因此需要新的预防和治疗药物。与此同时,日常临床实践中积累的关于AD诊断和对症治疗的信息作为真实世界数据存储,被认为是一种通过全面探索发现未知因素的有力手段,这些因素可能为AD的新预防和治疗方法提供线索。
我们使用了日本一家三级医疗和学术医院1981年至2016年的匿名医院信息系统数据,以寻找AD发病的潜在抑制因素,并验证所发现因素的有效性。我们首先对AD的候选抑制因素进行了全面搜索,并使用倾向评分的逆概率加权(IPW)方法对其进行验证。
通过全面搜索,我们确定甘草的成分甘草酸(GA)是一种候选的AD抑制因素,甘草是一种具有抗炎、抗氧化、抗菌和抗衰老特性的传统药物。IPW方法显示,调整后GA组患AD的优势比为0.642(95%置信区间:0.566 - 0.727),与非GA组相比。
这是第一项表明GA可能是能够抑制AD发病的因素的人体研究。此外,我们的方法可能是一种有前景的药物重新定位工具,即将临床已使用且副作用已知的现有药物应用于与其原始用途不同的疾病。