Harmol是一种具有口服活性的β-咔啉生物碱，同时作为TFEB激活剂和人类单胺氧化酶（MAO）强效抑制剂，具备广泛生物活性与明确作用机制。它能促进TFEB核转位，恢复自噬通量和溶酶体生物合成，通过自噬-溶酶体通路加速α-突触核蛋白降解，进而改善小鼠帕金森模型的运动损伤，发挥神经保护作用；还可诱导细胞有丝分裂、自噬和凋亡，拥有抗肿瘤、抗抑郁、延缓衰老、抗真菌、抗病毒及抗氧化活性，有望用于帕金森病等疾病的治疗。
[1] Xu J, Ao YL, Huang C, Song X, Zhang G, Cui W, Wang Y, Zhang XQ, Zhang Z. Harmol promotes α-synuclein degradation and improves motor impairment in Parkinson's models via regulating autophagy-lysosome pathway. NPJ Parkinsons Dis. 2022 Aug 6;8(1):100. doi: 10.1038/s41531-022-00361-4. PMID: 35933473; PMCID: PMC9357076.[2]Abe A, Kokuba H. Harmol induces autophagy and subsequent apoptosis in U251MG human glioma cells through the downregulation of survivin. Oncol Rep. 2013 Apr;29(4):1333-42. doi: 10.3892/or.2013.2242. Epub 2013 Jan 18. PMID: 23338618.[3]Abe A, Yamada H. Harmol induces apoptosis by caspase-8 activation independently of Fas/Fas ligand interaction in human lung carcinoma H596 cells. Anticancer Drugs. 2009 Jun;20(5):373-81. doi: 10.1097/CAD.0b013e32832a2dd9. PMID: 19318910.[4]Costa-Machado LF, Garcia-Dominguez E, McIntyre RL, Lopez-Aceituno JL, Ballesteros-Gonzalez Á, Tapia-Gonzalez A, Fabregat-Safont D, Eisenberg T, Gomez J, Plaza A, Sierra-Ramirez A, Perez M, Villanueva-Bermejo D, Fornari T, Loza MI, Herradon G, Hofer SJ, Magnes C, Madeo F, Duerr JS, Pozo OJ, Galindo MI, Del Pino I, Houtkooper RH, Megias D, Viña J, Gomez-Cabrera MC, Fernandez-Marcos PJ. Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models. Nat Commun. 2023 May 15;14(1):2779. doi: 10.1038/s41467-023-38410-y. PMID: 37188705; PMCID: PMC10185515.
