中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (6): 752-763.doi: 10.12092/j.issn.1009-2501.2026.06.004
• “糖尿病心血管并发症的药物进展”专栏 • 上一篇
郭苏1,2(
), 秦小江2,3, 江雪露2,4, 方梦薇1,2, 满志2,4, 孟欣2,4, 郑志发5, 赵良渊4, 施熠炜6, 侯晓敏1,2,*()
收稿日期:2025-07-23
出版日期:2026-06-26
发布日期:2026-07-06
通讯作者:
侯晓敏
E-mail:guosu142511@163.com;xiaominhou@sxmu.edu.cn
作者简介:郭苏，女，硕士研究生，研究方向：微血管药理学、病理生理学及天然产物的保护作用研究。E-mail：基金资助:
Su GUO1,2(), Xiaojiang QIN2,3, Xuelu JIANG2,4, Mengwei FANG1,2, Zhi MAN2,4, Xin MENG2,4, Zhifa ZHENG5, Liangyuan ZHAO4, Yiwei SHI6, Xiaomin HOU1,2,*()
Received:2025-07-23
Online:2026-06-26
Published:2026-07-06
Contact:
Xiaomin HOU
E-mail:guosu142511@163.com;xiaominhou@sxmu.edu.cn
摘要：
糖尿病是一种以慢性高血糖为特征的常见代谢性疾病。长期高血糖可损伤全身微血管，包括视网膜、肾小球、神经营养血管及心肌微小冠状动脉等，临床表现为糖尿病视网膜病变（diabetic retinopathy，DR）、糖尿病肾病（diabetic kidney disease，DKD）、糖尿病神经病变（diabetic neuropathy，DN）和糖尿病心肌病变（diabetic cardiomyopathy，DCM）。这些并发症严重影响患者生活质量，甚至危及生命。糖尿病微血管病变的发病机制与高血糖诱导的代谢途径异常激活、氧化应激及炎症反应等密切相关，最终导致微血管内皮功能损伤、基底膜增厚和微循环障碍。黄酮类化合物作为一类广泛存在于植物中的天然产物，具有抗炎、抗氧化和保护血管内皮等多种生物活性，在防治糖尿病微血管病变方面展现出巨大潜力。本文综述了近年来黄酮类化合物在该领域的研究进展，并探讨了其在临床应用中的挑战和未来发展方向，以期为后续开发和应用提供参考。
中图分类号:
郭苏, 秦小江, 江雪露, 方梦薇, 满志, 孟欣, 郑志发, 赵良渊, 施熠炜, 侯晓敏. 黄酮类化合物防治糖尿病微血管病变的研究进展[J]. 中国临床药理学与治疗学, 2026, 31(6): 752-763.
Su GUO, Xiaojiang QIN, Xuelu JIANG, Mengwei FANG, Zhi MAN, Xin MENG, Zhifa ZHENG, Liangyuan ZHAO, Yiwei SHI, Xiaomin HOU. Research progress on flavonoids in the prevention and treatment of diabetic microvascular complications[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(6): 752-763.
图 1
Fig.1 The basic molecular structure of flavonoids, classification, and biological activities
图 2
Fig.2 The pathogenesis of diabetic microvascular complications(by figdraw.com)
图 3
Fig.3 Pathological manifestations of diabetic microvascular complications in different target organs (by figdraw.com)
| Classification | Flavonoids | Sources | Mechanisms | Ref |
| Flavonols | Quercetin | Vegetables, tea, nuts, seed, fruits, red wine | (DR):↑ganglion cell number and retinal thickness, ↓ BRB breakdown, VEGF, ICAM-1 level, ↓ vascular permeability and leakage (DKD): ↓ EGFR/Erk1/2 signaling pathway → ↓ podocyte apoptosis,↑ Nrf2/HO-1 pathway → ↓ iron-driven lipid peroxidation (DN):↑Slit-2, Netrin-1 expression, ↓ Rho/ROCK signaling pathway overactivation →↑ nerve axon growth and regeneration,↑ nerve conduction ↑AMPK/PGC-1α pathway → ↓ mitochondrial morphology and dysfunction, ↓ ROS generation → protection of Schwann cells (DMC):↑ Nrf2 pathway → ↓ ROS level, cardiomyocyte apoptosis,↑ AMPK signaling pathway →↑ eNOS activity, microvascular density, blood flow | [ [ [ [ |
| Rutin | Buckwheat, tobacco, citrus fruits, tea, asparagus | (DN): ↓ NLRP3 inflammasome activity → ↓ IL-1β, IL-18 secretion,↑ blood perfusion (DCM):↑ capillary density, permeability →↑ myocardial perfusion ↓ MMP/TGF-β1 imbalance →↑ myocardial function, ↓cardiac remodeling | [ [ | |
| Kaempferol | Broccoli, apples, grapes, onions, herbs | (DR): ↓ERRα activity, ↓ cell proliferation, migration, tube formation, ↓ VEGF expression,↑TSP-1,ADAMTS-1 level→↓angiogenic effects (DKD): ↓RhoA/Rho kinase activity → ↓smooth muscle cell contraction and ECM hyperplasia,↑ hemodynamic disturbance | [ [ | |
| Flavanones | Hesperetin | Lemons, limes, Oranges, grapefruits, citrus | (DR):↑capillary resilience, maintain structural integrity, ↓fragility, and hemorrhage risk | [ |
| Naringenin naringin | Pomelos, lemons, limes, oranges, grapefruits, citrus | (DR):↑GTPCH1/eNOS pathway →↑eNOS activity and NO generation, retinal endothelial cells (DKD): ↓AGEs-RAGE, IL-1β, TNF-α levels → ↓ inflammatory cell adhesion and infiltration (DMC): ↓Bax/Caspase-3 expression → ↓ myocardial fibrosis, basement membrane thickness ↑ Nrf2 signaling, ↓ NF-κB signaling, ↓ ROS generation, and inflammatory cells →↑ cardiomyocytes, endothelial cells (DMC): induce ERK1/2, PKCδ, Akt phosphorylation →↑ Nrf2 nuclear translocation, antioxidant gene expression → ↓ apoptosis ↓ ROS level → ↓ mitochondrial membrane potential depolarization, Caspase-3 activity | [ [ [ [ | |
| Flavones | Luteolin | Lonicera japonica, peppermint, carrots, capsicum annuum, celery | (DR): modulation of the NLRP3/NOX4 signaling pathway→↓NLRP3,NOX4,TXNIP,NLRP1 expression,↓retinal cell apoptosis,↑integrity of the microvascular structure (DKD):↓ type IV collagen deposition，TGF-β1 level→↑basement membrane abnormalities (DN):↑Nrf2/HO-1 signaling pathway→↓MDA level,↑SOD activity,↓oxidative stress→↑nerve blood flow induction GAP-43 expression→neurite growth | [ [ [ |
| Baicalein baicalin | Scutellaria baicalensis | (DR):↓pVEGF-R2 level→↓NOX2 activity and ROS generation→↓oxidative damage of endothelial cells, ↓GFAP and VEGF expression in Müller cells, ↓vascular abnormality, and ganglion cell loss (DKD)↑Nrf2 signaling pathway,↑HO-1, NQO-1 expression→↓MDA,↑SOD,CAT level,↓Erk1/2, JNK,P38 phosphorylation→↓pro-inflammatory cytokines (IL-1β, IL-6, MCP-1, and TNF-α level) | [ [ | |
| Flavanols | Catechin | Tea, cocoa, grapes, apples, legumes | (DN):↑NO level, ↓ET-1level→↓nerve injury,↑nutritional support | [ |
| Epigallocatechin-3-gallate | Camellia sinensis | (DMC):↑AMPK/mTOR signaling pathway→↑cardiomyocyte,pericyte autophagy in microvessels ↓TGF-β1/MMPs signaling →↓myocardial interstitial deposition→↑microvascular function | [ | |
| Isoflavones | Genistein puerarin | Soybeans and other plants, Pueraria lobata | (DKD):↑SIRT1expression, AMPK/mTOR pathway→↑podocyte autophagy→↓urinary protein,renal injury (DN):↓oxidative stress, endothelial dysfunction ↑NGF level,microvascular dysfunction | [ [ |
表 1
Table 1 Flavonoids and their mechanism of action in diabetic microangiopathy
| Classification | Flavonoids | Sources | Mechanisms | Ref |
| Flavonols | Quercetin | Vegetables, tea, nuts, seed, fruits, red wine | (DR):↑ganglion cell number and retinal thickness, ↓ BRB breakdown, VEGF, ICAM-1 level, ↓ vascular permeability and leakage (DKD): ↓ EGFR/Erk1/2 signaling pathway → ↓ podocyte apoptosis,↑ Nrf2/HO-1 pathway → ↓ iron-driven lipid peroxidation (DN):↑Slit-2, Netrin-1 expression, ↓ Rho/ROCK signaling pathway overactivation →↑ nerve axon growth and regeneration,↑ nerve conduction ↑AMPK/PGC-1α pathway → ↓ mitochondrial morphology and dysfunction, ↓ ROS generation → protection of Schwann cells (DMC):↑ Nrf2 pathway → ↓ ROS level, cardiomyocyte apoptosis,↑ AMPK signaling pathway →↑ eNOS activity, microvascular density, blood flow | [ [ [ [ |
| Rutin | Buckwheat, tobacco, citrus fruits, tea, asparagus | (DN): ↓ NLRP3 inflammasome activity → ↓ IL-1β, IL-18 secretion,↑ blood perfusion (DCM):↑ capillary density, permeability →↑ myocardial perfusion ↓ MMP/TGF-β1 imbalance →↑ myocardial function, ↓cardiac remodeling | [ [ | |
| Kaempferol | Broccoli, apples, grapes, onions, herbs | (DR): ↓ERRα activity, ↓ cell proliferation, migration, tube formation, ↓ VEGF expression,↑TSP-1,ADAMTS-1 level→↓angiogenic effects (DKD): ↓RhoA/Rho kinase activity → ↓smooth muscle cell contraction and ECM hyperplasia,↑ hemodynamic disturbance | [ [ | |
| Flavanones | Hesperetin | Lemons, limes, Oranges, grapefruits, citrus | (DR):↑capillary resilience, maintain structural integrity, ↓fragility, and hemorrhage risk | [ |
| Naringenin naringin | Pomelos, lemons, limes, oranges, grapefruits, citrus | (DR):↑GTPCH1/eNOS pathway →↑eNOS activity and NO generation, retinal endothelial cells (DKD): ↓AGEs-RAGE, IL-1β, TNF-α levels → ↓ inflammatory cell adhesion and infiltration (DMC): ↓Bax/Caspase-3 expression → ↓ myocardial fibrosis, basement membrane thickness ↑ Nrf2 signaling, ↓ NF-κB signaling, ↓ ROS generation, and inflammatory cells →↑ cardiomyocytes, endothelial cells (DMC): induce ERK1/2, PKCδ, Akt phosphorylation →↑ Nrf2 nuclear translocation, antioxidant gene expression → ↓ apoptosis ↓ ROS level → ↓ mitochondrial membrane potential depolarization, Caspase-3 activity | [ [ [ [ | |
| Flavones | Luteolin | Lonicera japonica, peppermint, carrots, capsicum annuum, celery | (DR): modulation of the NLRP3/NOX4 signaling pathway→↓NLRP3,NOX4,TXNIP,NLRP1 expression,↓retinal cell apoptosis,↑integrity of the microvascular structure (DKD):↓ type IV collagen deposition，TGF-β1 level→↑basement membrane abnormalities (DN):↑Nrf2/HO-1 signaling pathway→↓MDA level,↑SOD activity,↓oxidative stress→↑nerve blood flow induction GAP-43 expression→neurite growth | [ [ [ |
| Baicalein baicalin | Scutellaria baicalensis | (DR):↓pVEGF-R2 level→↓NOX2 activity and ROS generation→↓oxidative damage of endothelial cells, ↓GFAP and VEGF expression in Müller cells, ↓vascular abnormality, and ganglion cell loss (DKD)↑Nrf2 signaling pathway,↑HO-1, NQO-1 expression→↓MDA,↑SOD,CAT level,↓Erk1/2, JNK,P38 phosphorylation→↓pro-inflammatory cytokines (IL-1β, IL-6, MCP-1, and TNF-α level) | [ [ | |
| Flavanols | Catechin | Tea, cocoa, grapes, apples, legumes | (DN):↑NO level, ↓ET-1level→↓nerve injury,↑nutritional support | [ |
| Epigallocatechin-3-gallate | Camellia sinensis | (DMC):↑AMPK/mTOR signaling pathway→↑cardiomyocyte,pericyte autophagy in microvessels ↓TGF-β1/MMPs signaling →↓myocardial interstitial deposition→↑microvascular function | [ | |
| Isoflavones | Genistein puerarin | Soybeans and other plants, Pueraria lobata | (DKD):↑SIRT1expression, AMPK/mTOR pathway→↑podocyte autophagy→↓urinary protein,renal injury (DN):↓oxidative stress, endothelial dysfunction ↑NGF level,microvascular dysfunction | [ [ |
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