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自噬作为黄酮类化合物在人类疾病中发挥保护作用的分子靶点。

Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease.

作者信息

Prieto-Domínguez Nestor, Garcia-Mediavilla Maria V, Sanchez-Campos Sonia, Mauriz Jose L, Gonzalez-Gallego Javier

机构信息

Institute of Biomedicine (IBIOMED), University of Leon, Leon, Spain.

Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.

出版信息

Curr Med Chem. 2018;25(7):814-838. doi: 10.2174/0929867324666170918125155.

Abstract

BACKGROUND

Autophagy is a cellular pathway with the ability to maintain cell homeostasis through the elimination of damaged or useless cellular components, and its deregulation may initiate or aggravate different human diseases. Flavonoids, a group of plant metabolites, are able to modulate different molecular and cellular processes including autophagy.

OBJECTIVE

To review the effects of flavonoids on autophagy pathway in both invasive and noninvasive human diseases, focusing on the global outcomes in their progression. Moreover, the efficacy of the combination of flavonoids with drugs or other natural nontoxic compounds was also reviewed.

METHODS

A literature search was performed to identify and analyze peer-reviewed publications containing and studies focused on autophagy deregulation in different proliferative and non-proliferative pathologies and the potential protective effects of flavonoids.

RESULTS

Analyzed publications indicated that imbalance between cell death and survival induced by changes in autophagy play an important role in the pathophysiology of a number of human diseases. The use of different flavonoids as autophagy modulators, alone or in combination with other molecules, might be a worthy strategy in the treatment of cancer, neurodegenerative disorders, cardiovascular diseases, hepatic diseases, leishmaniasis, influenza, gastric ulcers produced by infection, diabetes, asthma, age-related macular degeneration or osteoporosis.

CONCLUSION

Flavonoids could potentially constitute important adjuvant agents of conventional therapies in the treatment of autophagy deregulation-related diseases. Moreover, combined therapy may help to diminish the doses of those conventional treatments, leading to reduced drug-derivative side effects and to improved patients' survival.

摘要

背景

自噬是一种细胞途径,能够通过清除受损或无用的细胞成分来维持细胞稳态,其失调可能引发或加重不同的人类疾病。黄酮类化合物是一类植物代谢产物,能够调节包括自噬在内的不同分子和细胞过程。

目的

综述黄酮类化合物在侵袭性和非侵袭性人类疾病中对自噬途径的影响,重点关注其在疾病进展中的整体结果。此外,还综述了黄酮类化合物与药物或其他天然无毒化合物联合使用的疗效。

方法

进行文献检索,以识别和分析同行评审的出版物,这些出版物包含聚焦于不同增殖性和非增殖性疾病中自噬失调以及黄酮类化合物潜在保护作用的研究。

结果

分析的出版物表明,自噬变化引起的细胞死亡和存活之间的失衡在许多人类疾病的病理生理学中起重要作用。单独或与其他分子联合使用不同的黄酮类化合物作为自噬调节剂,可能是治疗癌症、神经退行性疾病、心血管疾病、肝脏疾病、利什曼病、流感、幽门螺杆菌感染引起的胃溃疡、糖尿病、哮喘、年龄相关性黄斑变性或骨质疏松症的一种有价值的策略。

结论

黄酮类化合物可能成为治疗自噬失调相关疾病的传统疗法的重要辅助剂。此外,联合治疗可能有助于减少那些传统治疗的剂量,从而减少药物衍生的副作用并提高患者的生存率。

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