Academic Journal
Efficacy of the monocarbonyl curcumin analog C66 in the reduction of diabetes-associated cardiovascular and kidney complications
| العنوان: | Efficacy of the monocarbonyl curcumin analog C66 in the reduction of diabetes-associated cardiovascular and kidney complications |
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| المؤلفون: | Mitko Mladenov, Jane Bogdanov, Bogdan Bogdanov, Nikola Hadzi-Petrushev, Andre Kamkin, Radoslav Stojchevski, Dimiter Avtanski |
| المصدر: | Molecular Medicine, Vol 28, Iss 1, Pp 1-16 (2022) |
| بيانات النشر: | BMC, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Therapeutics. Pharmacology LCC:Biochemistry |
| مصطلحات موضوعية: | Curcumin analogs, C66, Diabetes mellitus, Aorta, Heart, Kidney, Therapeutics. Pharmacology, RM1-950, Biochemistry, QD415-436 |
| الوصف: | Abstract Curcumin is a polyphenolic compound derived from turmeric that has potential beneficial properties for cardiovascular and renal diseases and is relatively safe and inexpensive. However, the application of curcumin is rather problematic due to its chemical instability and low bioavailability. The experimental results showed improved chemical stability and potent pharmacokinetics of one of its analogs – (2E,6E)-2,6-bis[(2-trifluoromethyl)benzylidene]cyclohexanone (C66). There are several advantages of C66, like its synthetic accessibility, structural simplicity, improved chemical stability (in vitro and in vivo), presence of two reactive electrophilic centers, and good electron-accepting capacity. Considering these characteristics, we reviewed the literature on the application of C66 in resolving diabetes-associated cardiovascular and renal complications in animal models. We also summarized the mechanisms by which C66 is preventing the release of pro-oxidative and pro-inflammatory molecules in the priming and in activation stage of cardiomyopathy, renal fibrosis, and diabetic nephropathy. The cardiovascular protective effect of C66 against diabetes-induced oxidative damage is Nrf2 mediated but mainly dependent on JNK2. In general, C66 causes inhibition of JNK2, which reduces cardiac inflammation, fibrosis, oxidative stress, and apoptosis in the settings of diabetic cardiomyopathy. C66 exerts a powerful antifibrotic effect by reducing inflammation-related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and CAV-1) and inducing the expression of anti-inflammatory factors (HO-1 and NEDD4), as well as targeting TGF-β/SMADs, MAPK/ERK, and PPAR-γ pathways in animal models of diabetic nephropathy. Based on the available evidence, C66 is becoming a promising drug candidate for improving cardiovascular and renal health. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1076-1551 1528-3658 |
| Relation: | https://doaj.org/toc/1076-1551; https://doaj.org/toc/1528-3658 |
| DOI: | 10.1186/s10020-022-00559-5 |
| URL الوصول: | https://doaj.org/article/d57bba6f185144f1850b50f988e985b8 |
| رقم الانضمام: | edsdoj.57bba6f185144f1850b50f988e985b8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10761551 15283658 |
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| DOI: | 10.1186/s10020-022-00559-5 |