Selected activities of Citrus maxima Merr. fruits on human endothelial cells: enhancing cell migration and delaying cellular aging.
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.
Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand. nohin@hotmail.com.
Paiwan
P
Buachan
Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani 12121, Thailand. ning.phd@gmail.com.
Linda
L
Chularojmontri
Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand. suvara@gmail.com.
Suvara K
SK
Wattanapitayakul
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects*; D002957:Citrus / Q000737:chemistry*; D044950:Flavanones / Q000494:pharmacology; D005452:Fluoresceins / Q000378:metabolism; D005638:Fruit / Q000737:chemistry*; D005707:Gallic Acid / Q000494:pharmacology; D006569:Hesperidin / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
C110400:2',7'-dichlorodihydrofluorescein diacetate; D000975:Antioxidants; D044950:Flavanones; D005452:Fluoresceins; D010936:Plant Extracts; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005707:Gallic Acid; D006569:Hesperidin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C005274:naringin; D001205:Ascorbic Acid