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松果菊苷-锌纳米材料通过抑制晚期糖基化终产物受体的转录激活抑制皮肤糖基化。

Echinacoside-Zinc Nanomaterial Inhibits Skin Glycation by Suppressing the Transcriptional Activation of the Receptor for Advanced Glycation End-Products.

机构信息

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.

Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300457, China.

出版信息

ACS Nano. 2023 Jul 25;17(14):14123-14135. doi: 10.1021/acsnano.3c04726. Epub 2023 Jul 5.

Abstract

Glycation is a nonenzymatically catalyzed spontaneous reaction that eventually leads to the formation of advanced glycation end-products (AGEs), which can bind to the receptor for AGEs (RAGE). The consequences are oxidative damage, an inflammatory response, and aging. In this work, we synthesized echinacoside-zinc coordination polymers (ECH-Zn) by using the coordination interaction between the catechol group of ECH and zinc ions. ECH-Zn was further wrapped with hyaluronic acid/poly (ethylenimine) (HA-PEI) to obtain spherical nanoparticle polymers of HA-PEI-coated ECH-Zn (PPZn). PPZn can enhance the uptake and utilization of ECH-Zn and also have a better antiglycation effect in the skin under the effect of promoting transdermal absorption of HA-PEI. Mechanistic studies at the cellular level showed that MDM2 can interact with STAT2 to form a transcriptional complex and thus promote RAGE transcriptional activation. and studies revealed that PPZn can decrease the expression and inhibit the interaction of the MDM2/STAT2 complex. It inhibited the function of the MDM2/STAT2 complex and suppressed the transcriptional activation of RAGE, thereby exerting antiglycation effects. In conclusion, this work provides a nanomaterial and elucidated a mechanism of anti-skin glycation.

摘要

糖基化是一种非酶促催化的自发反应,最终导致晚期糖基化终产物(AGEs)的形成,AGEs 可以与 AGEs 受体(RAGE)结合。其后果是氧化损伤、炎症反应和衰老。在这项工作中,我们通过 ECH 中儿茶酚基团与锌离子之间的配位相互作用合成了松果菊苷-锌配位聚合物(ECH-Zn)。ECH-Zn 进一步用透明质酸/聚(亚乙基亚胺)(HA-PEI)包裹,得到透明质酸/聚(亚乙基亚胺)包裹的 ECH-Zn(PPZn)的球形纳米粒子聚合物。PPZn 可以增强 ECH-Zn 的摄取和利用,并且在 HA-PEI 促进透皮吸收的作用下,在皮肤中具有更好的抗糖化作用。细胞水平的机制研究表明,MDM2 可以与 STAT2 相互作用形成转录复合物,从而促进 RAGE 的转录激活。和研究表明,PPZn 可以降低表达并抑制 MDM2/STAT2 复合物的相互作用。它抑制了 MDM2/STAT2 复合物的功能,并抑制了 RAGE 的转录激活,从而发挥抗糖化作用。总之,这项工作提供了一种纳米材料,并阐明了一种抗皮肤糖化的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fa0/10373517/44ce13656b1c/nn3c04726_0001.jpg

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