Targeting matrix metalloproteases in diabetic wound healing

Abstract

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.

Reactive Oxygen Species‐Scavenging Nanosystems in the Treatment of Diabetic Wounds

“…[ 35 ] ROS can enhance the stress state of functional cells, resulting in increased activity of signaling pathways secreting pro‐inflammatory cytokines, chemokines, and MMPs in damaged tissues, which are closely associated with difficult‐to‐heal wounds. [ 36 ] Therefore, ROS generation and clearance are necessary conditions to ensure the effectiveness and timeliness of wound healing.…”

Galangin: A food‐derived flavonoid with therapeutic potential against a wide spectrum of diseases

“…Recently, drugs derived from food to treat many diseases are gaining acceptance (Chen, Qin, et al, 2023; Chen, Zhong, et al, 2023). Flavonoids, as a bunch of polyphenolic compounds made in plants as secondary metabolites, are extensively exist in fruits, vegetables, and herbs, which have a wide range of biological activities (Chen et al, 2022).…”

“…Diabetes mellitus (DM), featured by persistent hyperglycemia, is a chronic metabolic noncommunicable disease that may impact over 783 million people globally by 2045 (Chen, Qin, et al, 2023). Although the exact pathogenesis is not fully elucidated, studies have shown that suppression of α‐glucosidase and non‐enzymatic glycation has been shown to be an effective approach to treat T2DM (Hossain et al, 2020).…”

Recent progress in nanozymes for the treatment of diabetic wounds

“…[7][8][9] Besides, continuous hyperglycemia in diabetic patients not only leads to impaired immune response but also provides nutrition for bacteria, resulting in diabetic wounds being more vulnerable to bacterial infection. 10 Persistent bacterial infection of diabetic wounds is one of the main causes of impaired wound healing. In response to this feature, topical antibiotics are usually used clinically to control bacterial infection.…”

“…[13][14][15][16][17][18][19] In addition to immunosuppression persistent high levels of glucose can lead to neurological, microvascular, and macrovascular lesions, which makes diabetic wounds difficult to heal. 10 Therefore, to accelerate the healing of diabetic wounds, we usually need to control blood glucose levels. In general, diabetics can control their blood glucose levels by injecting insulin.…”