GREDECO (Group of Research and Evaluation in Dermatology and Cosmetology), 69 Rue de la Tour, 75016 Paris, France.
Laboratoire Innotech International, 22 Avenue Aristide Briand, 94110 Arcueil, France.
Molecules. 2023 Jul 22;28(14):5591. doi: 10.3390/molecules28145591.
Diosmin is used to relieve chronic venous disease (CVD) symptoms. This study aimed to investigate the anti-inflammatory and antioxidant effects of diosmetin-3--β-d-glucuronide, the major metabolite of diosmin, using human skin explants. The explants were exposed to substance P (inflammation model) or UVB irradiation (oxidative model) and to five diosmetin-3--β-d-glucuronide concentrations. Inflammation was evaluated through interleukin-8 (IL-8) secretion measurements and capillary dilation observation, and oxidation was evaluated by measuring the hydrogen peroxide levels and observing cyclobutane pyrimidine dimers (CPDs). In substance-P-exposed explants, diosmetin-3--β-d-glucuronide induced a significant decrease in IL-8 secretions, with a maximal effect at 2700 pg/mL (-49.6%), and it reduced the proportion of dilated capillaries and the mean luminal cross-sectional area ( < 0.0001 at all tested concentrations), indicating a vasoconstrictive effect. In UVB-irradiated fragments, diosmetin-3--β-d-glucuronide induced a significant decrease in hydrogen peroxide production and in the number of CPD-positive cells, reaching a maximal effect at the concentration of 2700 pg/mL (-48.6% and -52.0%, respectively). Diosmetin-3--β-d-glucuronide induced anti-inflammatory and antioxidant responses, with the maximal effect being reached at 2700 pg/mL and corresponding to the peak plasma concentration estimated after the oral intake of 600 mg of diosmin, the daily dose usually recommended for the treatment of CVD. These ex vivo findings suggest a protective role of diosmetin-3--β-d-glucuronide against inflammatory and oxidative stress affecting the vascular system in CVD pathophysiology.
地奥司明用于缓解慢性静脉疾病 (CVD) 症状。本研究旨在利用人体皮肤标本研究地奥司明的主要代谢物地奥司明-3-O-β-D-葡萄糖醛酸苷的抗炎和抗氧化作用。标本分别暴露于 P 物质（炎症模型）或 UVB 照射（氧化模型）和 5 种地奥司明-3-O-β-D-葡萄糖醛酸苷浓度下。通过白细胞介素-8 (IL-8) 分泌测量和毛细血管扩张观察评估炎症，通过测量过氧化氢水平和观察环丁烷嘧啶二聚体 (CPD) 评估氧化。在 P 物质暴露的标本中，地奥司明-3-O-β-D-葡萄糖醛酸苷诱导 IL-8 分泌显著减少，最大效应浓度为 2700pg/mL（-49.6%），并减少扩张毛细血管的比例和平均管腔横截面积（所有测试浓度下均<0.0001），表明具有血管收缩作用。在 UVB 照射的标本中，地奥司明-3-O-β-D-葡萄糖醛酸苷诱导过氧化氢产生和 CPD 阳性细胞数量显著减少，最大效应浓度为 2700pg/mL（分别为-48.6%和-52.0%）。地奥司明-3-O-β-D-葡萄糖醛酸苷诱导抗炎和抗氧化反应，最大效应浓度为 2700pg/mL，对应于口服 600mg 地奥司明后的估计血浆峰值浓度，这是 CVD 治疗通常推荐的每日剂量。这些离体研究结果表明，地奥司明-3-O-β-D-葡萄糖醛酸苷在 CVD 病理生理学中具有针对影响血管系统的炎症和氧化应激的保护作用。
