Huang Fei, Mariani Nicole, Pariante Carmine M, Borsini Alessandra
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 Centre for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, PR China.
Brain Behav Immun Health. 2023 Aug 2;32:100674. doi: 10.1016/j.bbih.2023.100674. eCollection 2023 Oct.
Bile acids have been known to have both beneficial and detrimental effects on heart function, and as a consequence this can affect the brain. Inflammation is a key factor linking the heart and the brain, bile acids can reduce inflammation in the heart and, as a consequence, neuroinflammation, which may be due to the activation of different peripheral and central cellular and molecular mechanisms. Herein, we compile data published so far and summarise evidence demonstrating the effects of bile acids on myocardial cell viability and function, and its related mechanisms, in and studies conducted in homeostatic state or in models of cardiovascular diseases. Studies show that ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) do not affect the viability or contraction of cardiomyocytes in homeostatic state, and while UDCA has the capability to prevent the effect of hypoxia on reduced cell viability and beating rate, TUDCA can protect endoplasmic reticulum (ER) stress-induced apoptosis and cardiac contractile dysfunction. In contrast, deoxycholic acid (DCA) decreases contraction rate in homeostatic state, but it also prevents hypoxia-induced inflammation and oxidative stress, whereas lithocholic acid (LCA) can rescue doxazosin-induced apoptosis. Moreover, glycodeoxycholic acid (GDCA), cholic acid (CA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA) decrease contraction, whereas CDCA decreases cell viability in homeostatic conditions. The mechanisms underlying the aforementioned contrasting effects involve a differential regulation of the TGR5, MR and FXR receptors, as well as the cAMP signalling pathway. Overall, this review confirms the therapeutic potential of certain types of bile acids: UDCA, TUDCA, and potentially LCA, in cardiovascular diseases. By reducing inflammation in the heart, bile acids can improve heart-brain communication and promote overall health. Additional investigations are required to better elucidate mechanisms of action and more personalized clinical therapeutic doses.
已知胆汁酸对心脏功能既有有益影响，也有有害影响，因此这可能会影响大脑。炎症是连接心脏和大脑的关键因素，胆汁酸可以减轻心脏炎症，进而减轻神经炎症，这可能是由于不同的外周和中枢细胞及分子机制被激活所致。在此，我们汇总了迄今为止发表的数据，并总结了在稳态或心血管疾病模型中进行的体内和体外研究中，证明胆汁酸对心肌细胞活力和功能及其相关机制影响的证据。研究表明，在稳态下，熊去氧胆酸（UDCA）和牛磺熊去氧胆酸（TUDCA）不会影响心肌细胞的活力或收缩，虽然UDCA有能力预防缺氧对细胞活力降低和跳动率的影响，但TUDCA可以保护内质网（ER）应激诱导的细胞凋亡和心脏收缩功能障碍。相比之下，脱氧胆酸（DCA）在稳态下会降低收缩率，但它也能预防缺氧诱导的炎症和氧化应激，而石胆酸（LCA）可以挽救多沙唑嗪诱导的细胞凋亡。此外，甘氨脱氧胆酸（GDCA）、胆酸（CA）、鹅去氧胆酸（CDCA）、甘氨胆酸（GCA）、牛磺胆酸（TCA）、牛磺鹅去氧胆酸（TCDCA）和牛磺去氧胆酸（TDCA）会降低收缩，而CDCA在稳态条件下会降低细胞活力。上述相反作用的潜在机制涉及TGR5、MR和FXR受体以及cAMP信号通路的差异调节。总体而言，本综述证实了某些类型的胆汁酸：UDCA、TUDCA以及可能的LCA在心血管疾病中的治疗潜力。通过减轻心脏炎症，胆汁酸可以改善心脏与大脑之间的沟通并促进整体健康。需要进一步研究以更好地阐明作用机制和更个性化的临床治疗剂量。
