A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes.
A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes.
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综合分析天然产物作为SIRT6调节剂在阿尔茨海默病、衰老、癌症、炎症和糖尿病中的治疗应用
DOI：
10.3390/ijms22084180
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发表时间：
2021-04-17
影响因子：
5.6
通讯作者：
Kabir MT
中科院分区：
文献类型：
--
作者：
Akter R;Afrose A;Rahman MR;Chowdhury R;Nirzhor SSR;Khan RI;Kabir MT
天然产物长期以来一直被用作治疗各种人类疾病的药物。从天然来源中发现的先导化合物被用作开发更有效和更安全的药物的新模板。天然产物通过与生物大分子结合产生生物活性，因为天然产物补充了蛋白质结合位点，天然产物-蛋白质相互作用在自然界中已经优化。Sirtuin 6 （SIRT6）是一种NAD+依赖性组蛋白去乙酰化酶，是Sirtuin家族的独特成员。它在与DNA修复、肿瘤发生、糖酵解、糖异生、神经变性、心脏肥厚反应等相关的不同分子途径中起着至关重要的作用。因此，它已成为癌症、神经退行性疾病、衰老、糖尿病、代谢紊乱和心脏病等几种疾病的令人兴奋的靶点。最近的研究表明，天然化合物可以作为SIRT6的调节剂。在目前的综述中，已编制了SIRT6活性调节的天然产物、来源及其机制的清单。这些天然存在的SIRT6调节剂在改善主要人类疾病（如阿尔茨海默病、衰老、糖尿病、炎症和癌症）中的潜在应用也已被描述。天然产物如异槲皮素、木犀草素和花青素是SIRT6的激活剂，而牡荆素、儿茶素、黄花苷、岩藻多糖等是SIRT6的抑制剂。值得注意的是，槲皮素作为SIRT6激活剂和抑制剂的作用取决于其使用的浓度。虽然没有发现它们是SIRT6的高选择性和强效调节剂，但它们可以作为开发SIRT6的选择性和强效支架的起点。
Natural products have long been used as drugs to treat a wide array of human diseases. The lead compounds discovered from natural sources are used as novel templates for developing more potent and safer drugs. Natural products produce biological activity by binding with biological macromolecules, since natural products complement the protein-binding sites and natural product–protein interactions are already optimized in nature. Sirtuin 6 (SIRT6) is an NAD+ dependent histone deacetylase enzyme and a unique Sirtuin family member. It plays a crucial role in different molecular pathways linked to DNA repair, tumorigenesis, glycolysis, gluconeogenesis, neurodegeneration, cardiac hypertrophic responses, etc. Thus, it has emerged as an exciting target of several diseases such as cancer, neurodegenerative diseases, aging, diabetes, metabolic disorder, and heart disease. Recent studies have shown that natural compounds can act as modulators of SIRT6. In the current review, a list of natural products, their sources, and their mechanisms of SIRT6 activity modulation has been compiled. The potential application of these naturally occurring SIRT6 modulators in the amelioration of major human diseases such as Alzheimer’s disease, aging, diabetes, inflammation, and cancer has also been delineated. Natural products such as isoquercetin, luteolin, and cyanidin act as SIRT6 activators, whereas vitexin, catechin, scutellarin, fucoidan, etc. work as SIRT6 inhibitors. It is noteworthy to mention that quercetin acts as both SIRT6 activator and inhibitor depending on its concentration used. Although none of them were found as highly selective and potent modulators of SIRT6, they could serve as the starting point for developing selective and highly potent scaffolds for SIRT6.
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DOI：
10.1074/jbc.ra120.014883
发表时间：
2020-12-25
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
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影响因子：
3.8
作者：
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影响因子：
5.4
作者：
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影响因子：
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作者：
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DOI：
10.18632/aging.100023
发表时间：
2009-02-13
期刊：
Aging
影响因子：
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