Szymczyk Piotr, Majewska Małgorzata, Nowak Jadwiga
Department of Biology and Pharmaceutical Botany, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland.
Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Int J Mol Sci. 2025 Jan 20;26(2):848. doi: 10.3390/ijms26020848.
Tanshinones, biologically active diterpene compounds derived from , interact with specific proteins and DNA sequences, influencing signaling pathways in animals and humans. This study highlights tanshinone-protein interactions observed at concentrations achievable in vivo, ensuring greater physiological relevance compared to in vitro studies that often employ supraphysiological ligand levels. Experimental data suggest that while tanshinones interact with multiple proteomic targets, only a few enzymes are significantly affected at biologically relevant concentrations. This apparent paradox may be resolved by tanshinones' ability to bind DNA and influence enzymes involved in gene expression or mRNA stability, such as RNA polymerase II and human antigen R protein. These interactions trigger secondary, widespread changes in gene expression, leading to complex proteomic alterations. Although the current understanding of tanshinone-protein interactions remains incomplete, this study provides a foundation for deciphering the molecular mechanisms underlying the therapeutic effects of diterpenes. Additionally, numerous tanshinone derivatives have been developed to enhance pharmacokinetic properties and biological activity. However, their safety profiles remain poorly characterized, limiting comprehensive insights into their medicinal potential. Further investigation is essential to fully elucidate the therapeutic and toxicological properties of both native and modified tanshinones.
丹参酮是从[来源未提及]衍生而来的具有生物活性的二萜类化合物,它与特定的蛋白质和DNA序列相互作用,影响动物和人类的信号通路。这项研究突出了在体内可达到的浓度下观察到的丹参酮 - 蛋白质相互作用,与经常采用超生理配体水平的体外研究相比,确保了更高的生理相关性。实验数据表明,虽然丹参酮与多个蛋白质组学靶点相互作用,但在生物学相关浓度下只有少数酶受到显著影响。这种明显的矛盾可能通过丹参酮结合DNA并影响参与基因表达或mRNA稳定性的酶(如RNA聚合酶II和人类抗原R蛋白)的能力来解决。这些相互作用引发基因表达的继发性广泛变化,导致复杂的蛋白质组学改变。尽管目前对丹参酮 - 蛋白质相互作用的理解仍不完整,但这项研究为解读二萜类化合物治疗作用背后的分子机制奠定了基础。此外,已经开发了许多丹参酮衍生物以增强药代动力学性质和生物活性。然而,它们的安全性概况仍 poorly characterized,限制了对其药用潜力的全面了解。进一步的研究对于充分阐明天然和修饰丹参酮的治疗和毒理学性质至关重要。 (注:“poorly characterized”此处翻译为“表征不佳”,可能需要结合更专业知识进一步优化表述)