title: Morelloflavone, a biflavonoid inhibitor of migration-related kinases, ameliorates atherosclerosis in mice.
abstract: While macrophages take up modified LDL to form foam cells and multiply to develop fatty streaks, vascular smooth muscle cells (VSMC) migrate from the media to intima, secrete extracellular matrix, and increase the volume of atherosclerotic lesions. A medicinal plant Garcinia dulcis has been used in traditional Thai medicine for centuries to treat various chronic human diseases. Morelloflavone, a biflavonoid and an active ingredient of the plant, has been shown to inhibit VSMC migration through its inhibition of multiple migration-related kinases such as focal adhesion kinase, c-Src, ERK, and RhoA. However, the exact role of morelloflavone in atherosclerogenesis was unknown. We fed Ldlr(-/-)Apobec1(-/-) mice with either normal chow or chow containing 0.003% morelloflavone for 8 mo and assessed the extent of atherosclerosis by the en face and cross-sectional analyses. A cell composition analysis of atherosclerotic tissue was carried out using immunohistochemical staining. Oral morelloflavone therapy significantly reduced the atherosclerotic areas of the mouse aortas (a 26% reduction), without changing plasma lipid profiles or weights. Immunohistochemical analyses showed that morelloflavone reduced the number of VSMC in the atherosclerotic lesion while it did not change the density of macrophages in the lesion or the percentages of proliferating and apoptotic cells. Oral, low-dose, morelloflavone therapy retards atherosclerogenesis by limiting the migration of VSMC into the intima in the mouse model of human atherosclerosis. Upon further investigation, morelloflavone may be found to be a novel oral antiatherosclerotic agent and a viable addition to the conventional therapies such as statins in humans.
authors: Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
authors: Decha
authors: D
authors: Pinkaew
authors: Nongporn
authors: N
authors: Hutadilok-Towatana
authors: Ba-Bie
authors: BB
authors: Teng
authors: Wilawan
authors: W
authors: Mahabusarakam
authors: Ken
authors: K
authors: Fujise
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D044946:Biflavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D044946:Biflavonoids; D008055:Lipids; D011973:Receptors, LDL; C105620:morelloflavone; D010741:Phospholipases A; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase