Abstract
Cell migration is a critical process that is highly involved with normal and pathological conditions such as angiogenesis and wound healing. Important members of the RHO GTPase family are capable of controlling cytoskeleton conformation and altering motility characteristics of cells. There is a well-known relationship between small GTPases and the PI3K/AKT pathway. Endothelial cell migration can lead to angiogenesis, which is highly linked to wound healing processes. Phenolics, flavonoids, and anthocyanins are major groups of phytochemicals and are abundant in many natural products. Their antioxidant, antimicrobial, anti-inflammatory, antidiabetic, angiogenenic, neuroprotective, hepatoprotective, and cardioprotective properties have been extensively documented. This comprehensive review focuses on the in vitro and in vivo role of berry extracts and single anthocyanin and phenolic acid compounds on cell migration and angiogenesis. We aim to summarize the most recent published studies focusing on the experimental model, type of berry extract, source, dose/concentration and overall effect(s) of berry extracts, anthocyanins, and phenolic acids on the above processes.
Highlights
We focused on the in vitro and in vivo studies using berry extracts and single anthocyanin and phenolic acid compounds and their role on cell migration and angiogenesis (Tables 1 and 2)
We conclude that the majority of studies document the anti-angiogenic role of anthocyanins, but results are mixed on the role of phenolic acids on cell migration and angiogenesis and the signaling pathways they modulate as they relate to chronic disease
The type of animal model used and the disease state targeted may contribute to the conflicting results. This calls for scientific collaboration in the use of common extracts and/or bioactive compounds as well as similar experimental design and protocols to make valid conclusions
Summary
One fundamental process common to cell morphogenesis, immune function, regeneration, and disease is cell migration [1,2]. Chemotaxis, haptotaxis, and mechanotaxis are the three major mechanisms that are utilized by endothelial cells during migration and angiogenesis [2,3]. The cell establishes a front-to-rear polarity axis involving small GTPases including RHOA, RAC and CDC42, members of the Rho family and RAC is involved in the formation of lamellipodia at the leading edge of migrating cells [4]. Nutrients 2019, 11, 1075 required during focal adhesions while CDC42 is not directly involved in cell migration/movement but is essential for cell polarity that controls the direction of cell movement [4]. Promotion of cell migration is crucial in processes such as wound healing and tissue regeneration/renewal associated with burns, diabetes mellitus, ischemic conditions, and aging. In many chronic diseases such as atherosclerosis, tumor growth, and various fibrotic conditions, excessive cell migration results in enhanced invasion of cells across an extracellular matrix [3]
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