Xanthohumol Modulates Inflammation, Oxidative Stress, and Angiogenesis in Type 1 Diabetic Rat Skin Wound Healing

Abstract

Type 1 diabetes mellitus is responsible for metabolic dysfunction, accompanied by chronic inflammation, oxidative stress, and endothelium dysfunction, and is often associated with impaired wound healing. Phenol-rich food improves vascular function, contributing to diabetes prevention. This study has evaluated the effect of phenol-rich beverage consumption in diabetic rats on wound healing, through angiogenesis, inflammation, and oxidative stress modulation. A wound-healing assay was performed in streptozotocin-induced diabetic Wistar rats drinking water, 5% ethanol, and stout beer with and without 10 mg/L xanthohumol (1), for a five-week period. Wounded skin microvessel density was reduced to normal values upon consumption of 1 in diabetic rats, being accompanied by decreased serum VEGF-A and inflammatory markers (IL-1β, NO, N-acetylglucosaminidase). Systemic glutathione and kidney and liver H2O2, 3-nitrotyrosine, and protein carbonylation also decreased to healthy levels after treatment with 1, implying an improvement in oxidative stress status. These findings suggest that consumption of xanthohumol (1) by diabetic animals consistently decreases inflammation and oxidative stress, allowing neovascularization control and improving diabetic wound healing.

Modulation of VEGF signaling in a mouse model of diabetes by xanthohumol and 8‐prenylnaringenin: Unveiling the angiogenic paradox and metabolism interplay

“…In contrast, these animals exhibit a reduction in the number of vessels in left ventricle, which can be explained by the decreased VEGF‐A levels and VEGFR‐2 signaling pathway impairment. Circulating VEGF‐A levels in these experimental groups are decreased in accordance to other studies , but this systemic biomarker is a poor angiogenesis indicator, as the systemic levels did not correspond to the ones quantified in organs from T2DM animals (Fig. ).…”

“…Briefly, starting from acetylation of commercially available naringenin, the 7,4’‐diacethyl‐naringenin derivative was O ‐prenylated by the Mitsunobu reaction and following the tandem Claisen‐Cope rearrangement of 5‐prenyl‐7,4‐diacetylnaringenin with Eu(fod) 3 , 8PN was obtained in 32% yield. XN and 8PN were administered in a dose of 10 mg/L previously studied by our group, equivalent to 1 mg/kg/day, which is in line with the doses reported previously without displaying hepatotoxic effects . Polyphenols consumption was administered throughout the 20 weeks of experiment, the duration necessary to establish hyperglycemic conditions.…”

Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis

“…Furthermore, Nrf2 has been suggested to play a key coordinator as protecting cells against oxidative and inflammatory insults [34]. Xanthohumol (Xn) has been shown to induce Nrf2 activation in human hepatocytes and PC12 cells [30], [35], and display various biological activities, such as anti-inflammatory and antioxidant properties in streptozotocin-induced diabetic Wistar rats [28]. In the present study, we aimed to investigating whether Xn could mediate Nrf2 signaling pathway, conferring an antioxidant and anti-inflammatory properties to prevent from LPS-induced ALI mice.…”

“…1A), the principal prenylflavonoid that exists mainly in the hop plants ( Humulus lupulus L . ), is exploited for preserving and flavoring beer which has been attracted considerable attention because of its various biological activities, including anti-inflammatory and antioxidant properties [28]. Furthermore, recent studies also uncovered that Xn can positively regulate AMPK activity contributing to activate Nrf2 antioxidative signaling pathways, suggesting that it effectively improved oxidative-stress-induced cell injury [29], [30].…”

Fibroblast-Endothelial Partners for Vascularization Strategies in Tissue Engineering

“…Proteins were quantified using a microplate reader (Thermo, Electron Corporation) at 550 nm. 30 Western blot analysis Proteins were separated according to their molecular weight using SDS polyacrylamide gel electrophoresis (SDS-PAGE). Briefly, 10 mg of cell proteins were mixed with loading buffer (250 mM Tris-HCl pH 6.8, 8% SDS, 40% Glycerol, 0.04% Bromophenol blue [1:4], and dithiothreitol [DTT 1M, 1:20]), being then denatured at 99°C.…”