Endogenous Conjugation of Biomimetic Dinitrosyl Iron Complex with Protein Vehicles for Oral Delivery of Nitric Oxide to Brain and Activation of Hippocampal Neurogenesis
| العنوان: | Endogenous Conjugation of Biomimetic Dinitrosyl Iron Complex with Protein Vehicles for Oral Delivery of Nitric Oxide to Brain and Activation of Hippocampal Neurogenesis |
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| المؤلفون: | Tsai-Te Lu, Yi-Da Huang, Hung-Chi Chen, Ting-Yu Chin, I-Jui Hsu, Yi-Jen Hseuh, Hsin-Tzu Hsieh, Cheng-Ru Wu, Trinh Kieu Dinh, Chih-Wen Pao, Yong-Huei Hong, Ting-Shan Chan, Ping-Ching Wu, Manmath Narwane, Ya-Hsin Liu, Yunching Chen, Yu-Hsiang Chang |
| المصدر: | JACS Au, Vol 1, Iss 7, Pp 998-1013 (2021) JACS Au |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | dinitrosyl iron complex, Gastrointestinal tract, biology, Neurogenesis, Serum albumin, Endogeny, protein vehicle, Prodrug, Pharmacology, Article, Nitric oxide, neurogenesis, Chemistry, chemistry.chemical_compound, chemistry, nitric oxide, Oral administration, Paracellular transport, drug delivery, biology.protein, QD1-999 |
| الوصف: | Nitric oxide (NO), a pro-neurogenic and antineuroinflammatory gasotransmitter, features the potential to develop a translational medicine against neuropathological conditions. Despite the extensive efforts made on the controlled delivery of therapeutic NO, however, an orally active NO prodrug for a treatment of chronic neuropathy was not reported yet. Inspired by the natural dinitrosyl iron unit (DNIU) [Fe(NO)2], in this study, a reversible and dynamic interaction between the biomimetic [(NO)2Fe(μ-SCH2CH2OH)2Fe(NO)2] (DNIC-1) and serum albumin (or gastrointestinal mucin) was explored to discover endogenous proteins as a vehicle for an oral delivery of NO to the brain after an oral administration of DNIC-1. On the basis of the in vitro and in vivo study, a rapid binding of DNIC-1 toward gastrointestinal mucin yielding the mucin-bound dinitrosyl iron complex (DNIC) discovers the mucoadhesive nature of DNIC-1. A reversible interconversion between mucin-bound DNIC and DNIC-1 facilitates the mucus-penetrating migration of DNIC-1 shielded in the gastrointestinal tract of the stomach and small intestine. Moreover, the NO-release reactivity of DNIC-1 induces the transient opening of the cellular tight junction and enhances its paracellular permeability across the intestinal epithelial barrier. During circulation in the bloodstream, a stoichiometric binding of DNIC-1 to the serum albumin, as another endogenous protein vehicle, stabilizes the DNIU [Fe(NO)2] for a subsequent transfer into the brain. With aging mice under a Western diet as a disease model for metabolic syndrome and cognitive impairment, an oral administration of DNIC-1 in a daily manner for 16 weeks activates the hippocampal neurogenesis and ameliorates the impaired cognitive ability. Taken together, these findings disclose the synergy between biomimetic DNIC-1 and endogenous protein vehicles for an oral delivery of therapeutic NO to the brain against chronic neuropathy. |
| تدمد: | 2691-3704 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::582812bc1c855c625cd63b399c5a34eaTest https://doi.org/10.1021/jacsau.1c00160Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....582812bc1c855c625cd63b399c5a34ea |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 26913704 |
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