3 research outputs found
The coming age of flavonoids in the treatment of diabetic complications
Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the
biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and
treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding
therapies to prevent or retard the progression of diabetic complications remains an unmet need
due to the complexity of mechanisms involved, which include inflammation, oxidative stress and
angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown
to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their
potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds
as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro
and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent
pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic
complications. In brief, we provide updated information concerning the discrepancy between the
numerous experimental studies supporting the eficacy of flavonoids on diabetic complications and
the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects
on different mechanisms involved in diabetic complications, the excellent tolerability and low cost,
future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugsThis paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130,
PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093,
RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society
of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing
research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the
joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness
Nephroprotective effects of synthetic flavonoid hidrosmin in experimental diabetic nephropathy
Diabetes mellitus (DM) is a highâimpact disease commonly characterized by hyperglycemia, inflammation, and oxidative stress. Diabetic nephropathy (DN) is a common diabetic microvascular complication and the leading cause of chronic kidney disease worldwide. This study investigates the protective effects of the synthetic flavonoid hidrosmin (5âOâ(beta-hydroxyethyl) diosmin) in experimental DN induced by streptozotocin injection in apolipoprotein E deficient mice. Oral administration of hidrosmin (300 mg/kg/day, n = 11) to diabetic mice for 7 weeks markedly reduced albuminuria (albuminâtoâcreatinine ratio: 47 ± 11% vs. control) and ameliorated renal pathological damage and expression of kidney injury markers. Kidneys of hidrosminâtreated mice exhibited lower content of macrophages and T cells, reduced expression of cytokines and chemokines, and attenuated inflammatory signaling pathways. Hidrosmin treatment improved the redox balance by reducing prooxidant enzymes and enhancing antioxidant genes, and also decreased senescence markers in diabetic kidneys. In vitro, hidrosmin doseâdependently reduced the expression of inflammatory and oxidative genes in tubuloepithelial cells exposed to either highâglucose or cytokines, with no evidence of cytotoxicity at effective concentrations. In conclusion, the synthetic flavonoid hidrosmin exerts a beneficial effect against DN by reducing inflammation, oxidative stress, and senescence pathways. Hidrosmin could have a potential role as a coadjutant therapy for the chronic complications of DM.This work was supported by grants from the Spanish Ministry of Science and Innovation-
FEDER funds (Retos ColaboraciĂłn RTC2017-6089-1 and Retos InvestigaciĂłn RTI2018-098788-B-I00)
and Instituto de Salud Carlos III (PI20/00487 and DTS 19/00093
The Synthetic Flavonoid Hidrosmin Improves Endothelial Dysfunction and Atherosclerotic Lesions in Diabetic Mice
In diabetes, chronic hyperglycemia, dyslipidemia, inflammation and oxidative stress contribute to the progression of macro/microvascular complications. Recently, benefits of the use of flavonoids in these conditions have been established. This study investigates, in two different mouse models of diabetes, the vasculoprotective effects of the synthetic flavonoid hidrosmin on endothelial dysfunction and atherogenesis. In a type 2 diabetes model of leptin-receptor-deficient (db/db) mice, orally administered hidrosmin (600 mg/kg/day) for 16 weeks markedly improved vascular function in aorta and mesenteric arteries without affecting vascular structural properties, as assessed by wire and pressure myography. In streptozotocin-induced type 1 diabetic apolipoprotein E-deficient mice, hidrosmin treatment for 7 weeks reduced atherosclerotic plaque size and lipid content; increased markers of plaque stability; and decreased markers of inflammation, senescence and oxidative stress in aorta. Hidrosmin showed cardiovascular safety, as neither functional nor structural abnormalities were noted in diabetic hearts. Ex vivo, hidrosmin induced vascular relaxation that was blocked by nitric oxide synthase (NOS) inhibition. In vitro, hidrosmin stimulated endothelial NOS activity and NO production and downregulated hyperglycemia-induced inflammatory and oxidant genes in vascular smooth muscle cells. Our results highlight hidrosmin as a potential add-on therapy in the treatment of macrovascular complications of diabetes