Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai R&D Center for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, PR China.
Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
Brain Behav Immun. 2022 Jan;99:132-146. doi: 10.1016/j.bbi.2021.09.021. Epub 2021 Sep 30.
Bile acids, mainly ursodeoxycholic acid (UDCA) and its conjugated species glycoursodeoxycholic acid (GUDCA) and tauroursodeoxycholic acid (TUDCA) have long been known to have anti-apoptotic, anti-oxidant and anti-inflammatory properties. Due to their beneficial actions, recent studies have started to investigate the effect of UDCA, GUDCA, TUDCA on the same mechanisms in pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders, where increased cell apoptosis, oxidative stress and inflammation in the brain are often observed. A total of thirty-five pre-clinical studies were identified through PubMed/Medline, Web of Science, Embase, PsychInfo, and CINAHL databases, investigating the role of the UDCA, GUDCA and TUDCA in the regulation of brain apoptosis, oxidative stress and inflammation, in pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders. Findings show that UDCA reduces apoptosis, reactive oxygen species (ROS) and tumour necrosis factor (TNF)-α production in neurodegenerative models, and reduces nitric oxide (NO) and interleukin (IL)-1β production in neuropsychiatric models; GUDCA decreases lactate dehydrogenase, TNF-α and IL-1β production in neurological models, and also reduces cytochrome c peroxidase production in neurodegenerative models; TUDCA decreases apoptosis in neurological models, reduces ROS and IL-1β production in neurodegenerative models, and decreases apoptosis and TNF-α production, and increases glutathione production in neuropsychiatric models. In addition, findings suggest that all the three bile acids would be equally beneficial in models of Huntington's disease, whereas UDCA and TUDCA would be more beneficial in models of Parkinson's disease and Alzheimer's disease, while GUDCA in models of bilirubin encephalopathy and TUDCA in models of depression. Overall, this review confirms the therapeutic potential of UDCA, GUDCA and TUDCA in neurological, neurodegenerative and neuropsychiatric disorders, proposing bile acids as potential alternative therapeutic approaches for patients suffering from these disorders.
胆汁酸，主要是熊去氧胆酸（UDCA）及其共轭甘氨熊去氧胆酸（GUDCA）和牛磺熊去氧胆酸（TUDCA），长期以来一直具有抗细胞凋亡、抗氧化和抗炎作用。由于其有益的作用，最近的研究开始调查 UDCA、GUDCA、TUDCA 在神经、神经退行性和神经精神疾病的临床前模型中对相同机制的影响，在这些模型中，大脑中的细胞凋亡、氧化应激和炎症增加。通过 PubMed/Medline、Web of Science、Embase、PsychInfo 和 CINAHL 数据库共确定了 35 项临床前研究，调查 UDCA、GUDCA 和 TUDCA 在神经、神经退行性和神经精神疾病的临床前模型中调节大脑细胞凋亡、氧化应激和炎症的作用。研究结果表明，UDCA 可减少神经退行性模型中的细胞凋亡、活性氧（ROS）和肿瘤坏死因子（TNF）-α的产生，并减少神经精神疾病模型中的一氧化氮（NO）和白细胞介素（IL）-1β的产生；GUDCA 可减少神经疾病模型中的乳酸脱氢酶、TNF-α和 IL-1β的产生，也可减少神经退行性模型中的细胞色素 c 过氧化物酶的产生；TUDCA 可减少神经疾病模型中的细胞凋亡，减少神经退行性模型中的 ROS 和 IL-1β的产生，减少神经精神疾病模型中的细胞凋亡和 TNF-α的产生，增加谷胱甘肽的产生。此外，研究结果表明，在亨廷顿病模型中，所有三种胆汁酸的疗效相当，而 UDCA 和 TUDCA 在帕金森病和阿尔茨海默病模型中更有效，而 GUDCA 在胆红素脑病模型中更有效，TUDCA 在抑郁症模型中更有效。总的来说，本综述证实了 UDCA、GUDCA 和 TUDCA 在神经、神经退行性和神经精神疾病中的治疗潜力，提出了胆汁酸作为这些疾病患者潜在的替代治疗方法。
