Flavonoids as Potential Wound-Healing Molecules: Emphasis on Pathways Perspective

Abstract

Wounds are considered to be a serious problem that affects the healthcare sector in many countries, primarily due to diabetes and obesity. Wounds become worse because of unhealthy lifestyles and habits. Wound healing is a complicated physiological process that is essential for restoring the epithelial barrier after an injury. Numerous studies have reported that flavonoids possess wound-healing properties due to their well-acclaimed anti-inflammatory, angiogenesis, re-epithelialization, and antioxidant effects. They have been shown to be able to act on the wound-healing process via expression of biomarkers respective to the pathways that mainly include Wnt/β-catenin, Hippo, Transforming Growth Factor-beta (TGF-β), Hedgehog, c-Jun N-Terminal Kinase (JNK), NF-E2-related factor 2/antioxidant responsive element (Nrf2/ARE), Nuclear Factor Kappa B (NF-κB), MAPK/ERK, Ras/Raf/MEK/ERK, phosphatidylinositol 3-kinase (PI3K)/Akt, Nitric oxide (NO) pathways, etc. Hence, we have compiled existing evidence on the manipulation of flavonoids towards achieving skin wound healing, together with current limitations and future perspectives in support of these polyphenolic compounds as safe wound-healing agents, in this review.

Carbopol 940-based hydrogels loading synergistic combination of quercetin and luteolin from the herbEuphorbia humifusato promoteStaphylococcus aureusinfected wound healing

“…39 Numerous studies have demonstrated that the flavonoids and Carbopol 940 hydrogel possess wound-healing properties due to their well-acclaimed anti-inflammatory, antioxidant, re-epithelialization, and angiogenesis effects. 14,40–43 In our previous report, QU in combination with LU enhanced the antibacterial and antibiofilm efficacy synergistically, decreasing the membrane permeability and down-regulating the expression of multiple biofilm-related genes. 30 Besides, QU and LU are known for their powerful anti-inflammatory and antioxidant potency due to the resonance stability of the phenoxyl radical, 31,32 which support their potential use in wound healing.…”

Architecture of a dual biocompatible platform to immobilize genistin: Fabrication with physio-chemical and in vitro evaluation

“…The micrograph of the nano bers seeded with cells showed that the L929 in sample 4 with 40% nano-encapsulated genistin and 150 min electrospinning time is best attached and proliferated on the nano bers. On one side, the avonoid structure of genistin and its immobilization in nano bers make it easily absorbed by L929 cells 37 ; on the other side, the hydrophilic two-component PVA/GE provides biochemical signals to promote cell adhesion, migration, proliferation, and differentiation 38 .…”

Natural Polymeric Hydrogels Encapsulating Small Molecules for Diabetic Wound Healing

“…The healing time of diabetic wounds is longer due to an excessive and abnormal accumulation of several compounds like advanced glycation end products (AGEs) and reactive oxygen species (ROS), pro-/anti-inflammatory cytokines balance, interleukins, leukotrienes and complement factors at the wound site, but also to lack of ECM proteins [28]. The accumulation of AGEs can alter keratinocyte and fibroblast function.…”

“…Much research has shown that flavonoids, such as curcumin, hesperidin, luteolin, quercetin, kaempferol, apigenin, rutin, naringin, morin, mangiferin have potential for the management of diabetic wounds through stimulation of ECM synthesis and angiogenesis, and modulation of growth factors (Table 1). Thus, curcumin accelerated the healing process by reducing inflammation and had an apoptotic effect in the early stages of wound healing [28]. Luteolin significantly reduced the expression of inflammatory factors, such as IL-1, IL-6 and TNF-α and reduced the levels of prostaglandin E2, interferon and leukotriene B4 [28].…”