State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, China.
Front Immunol. 2023 Feb 17;14:1089001. doi: 10.3389/fimmu.2023.1089001. eCollection 2023.
Chronic inflammation participates in the progression of multiple chronic diseases, including obesity, diabetes mellitus (DM), and DM related complications. Diabetic ulcer, characterized by chronic wounds that are recalcitrant to healing, is a serious complication of DM tremendously affecting the quality of life of patients and imposing a costly medical burden on society. Matrix metalloproteases (MMPs) are a family of zinc endopeptidases with the capacity of degrading all the components of the extracellular matrix, which play a pivotal part in healing process under various conditions including DM. During diabetic wound healing, the dynamic changes of MMPs in the serum, skin tissues, and wound fluid of patients are in connection with the degree of wound recovery, suggesting that MMPs can function as essential biomarkers for the diagnosis of diabetic ulcer. MMPs participate in various biological processes relevant to diabetic ulcer, such as ECM secretion, granulation tissue configuration, angiogenesis, collagen growth, re-epithelization, inflammatory response, as well as oxidative stress, thus, seeking and developing agents targeting MMPs has emerged as a potential way to treat diabetic ulcer. Natural products especially flavonoids, polysaccharides, alkaloids, polypeptides, and estrogens extracted from herbs, vegetables, as well as animals that have been extensively illustrated to treat diabetic ulcer through targeting MMPs-mediated signaling pathways, are discussed in this review and may contribute to the development of functional foods or drug candidates for diabetic ulcer therapy. This review highlights the regulation of MMPs in diabetic wound healing, and the potential therapeutic ability of natural products for diabetic wound healing by targeting MMPs.
慢性炎症参与多种慢性疾病的进展，包括肥胖、糖尿病（DM）和 DM 相关并发症。糖尿病溃疡是 DM 的一种严重并发症，其特征为慢性难以愈合的伤口，极大地影响了患者的生活质量，并给社会带来了昂贵的医疗负担。基质金属蛋白酶（MMPs）是一类锌内肽酶，能够降解细胞外基质的所有成分，在包括 DM 在内的各种情况下的愈合过程中起着关键作用。在糖尿病伤口愈合过程中，患者血清、皮肤组织和伤口液中 MMPs 的动态变化与伤口恢复程度有关，提示 MMPs 可作为糖尿病溃疡诊断的重要生物标志物。MMPs 参与与糖尿病溃疡相关的各种生物学过程，如 ECM 分泌、肉芽组织形成、血管生成、胶原生长、再上皮化、炎症反应和氧化应激，因此，寻找和开发针对 MMPs 的药物已成为治疗糖尿病溃疡的一种潜在方法。天然产物，特别是从草药、蔬菜和动物中提取的黄酮类、多糖、生物碱、多肽和雌激素，已被广泛证明可通过靶向 MMPs 介导的信号通路来治疗糖尿病溃疡，本文对其进行了讨论，可能有助于开发治疗糖尿病溃疡的功能性食品或药物候选物。本文综述了 MMPs 在糖尿病伤口愈合中的调控作用，以及天然产物通过靶向 MMPs 治疗糖尿病伤口愈合的潜在治疗能力。
