Abstract
Endothelial injury and damage as well as accumulated reactive oxygen species (ROS) in aging play a significant role in the development of cardiovascular disease (CVD). Recent studies show an association of high citrus fruit intake with a lower risk of CVD and stroke but the mechanisms involved are not fully understood. This study investigated the effects of pummelo (Citrus maxima Merr. var. Tubtim Siam, CM) fruit extract on human umbilical vein endothelial cell (HUVECs) migration and aging. The freeze-dried powder of fruit extract was characterized for antioxidant capacity (FRAP assay) and certain natural antioxidants, including ascorbic acid, gallic acid, hesperidin, and naringin (HPLC). Short-term (48 h) co-cultivation of HUVECs with CM enhanced cell migration as evaluated by a scratch wound assay and Boyden chamber assay. A long-term treatment with CM for 35 days significantly increased HUVEC proliferation capability as indicated by population doubling level (PDL). CM also delayed the onset of aging phenotype shown by senescence-associated β-galactosidase (SA-β-gal) staining. Furthermore, CM was able to attenuate increased ROS levels in aged cells when determined by 2′,7′-dichlorodihydrofluorescein diacetate (DCDHF) while eNOS mRNA expression was increased but the eNOS protein level was not changed. Thus, further in vivo and clinical studies are warranted to support the use of pummelo as a functional fruit for endothelial health and CVD risk reduction.
Highlights
Citrus fruits are among the most valuable functional diets shown to lower oxidative-related disease risks, cardiovascular disease (CVD) [1,2]
A unified pattern observed in endothelial cells under oxidative stress and aging is the impairment of nitric oxide (NO) production and reduction of NO bioavailability due to oxidative destruction by reactive oxygen species (ROS) [4]
Endothelial damage is an initial insult to the vessel wall, where subsequent phenomena lead to macrophage infiltration, proliferation of smooth muscle cells, and vascular remodeling [5]
Summary
Citrus fruits are among the most valuable functional diets shown to lower oxidative-related disease risks, cardiovascular disease (CVD) [1,2]. In CVD, the endothelium is the main target of ROS-induced tissue injury, leading to endothelial dysfunction and premature aging: the aging process is an independent risk factor for the development of CVD. Endothelial damage is an initial insult to the vessel wall, where subsequent phenomena lead to macrophage infiltration, proliferation of smooth muscle cells, and vascular remodeling [5]. Substances that promote endothelial cell migration or enhance regenerative capacity of EPCs may have an important role in endothelial tissue repair, restoration of endothelial function, and reduction of CVD risks
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