Formation of Lysophosphatidic Acid, a Wound-Healing Lipid, during Digestion of Cabbage Leaves

Abstract

Lysophosphatidic acid (LPA) is a lipid mediator that plays a role in the process of wound healing in animal tissues, including the digestive tract. We determined LPA in several foodstuffs, and found that cabbage leaves were the richest source of LPA. We also found that, at 22 and 195 nmol/g (wet weight), LPA and phosphatidic acid (PA) were respectively formed during mastication of raw cabbage leaves and that the resulting PA was converted to LPA by pancreatic phospholipase A(2). The lipid extract obtained from ground cabbage leaves promoted the proliferation of Swiss 3T3 fibroblasts and the motility of HGC-27 cells, stomach-derived epithelial-like cells, at physiologically relevant concentrations. These activities of cabbage lipids were inhibited by Ki16425, an LPA-receptor antagonist. LPA formed during the digestion of cabbage leaves may be one of the components in the beneficial effect of ingested cabbage on a damaged digestive tract.

Plant Lysophosphatidic Acids: A Rich Source for Bioactive Lysophosphatidic Acids and Their Pharmacological Applications

“…Tanaka et al showed that LPAs from cabbage leaf induced the proliferation and migration of 3T3 fibroblasts and also showed that this cell expresses endogenous LPA1, LPA2 and LPA4 receptor subtypes. 7) In addition, LPAs from cabbage increased the migration of the gastric epithelium-like cell line, showed that oral administration of LPA as well as phosphatidic acid attenuates aspirin-induced stomach mucosal injury, further supporting the idea that LPA could be used to attenuate aspirin side-effects in the stomach. 18) In addition, LPAs in soybean lecithin also exhibited anti-gastric ulcer activity.…”

“…5) In addition, Tanaka et al reported that vegetables such as cabbage, broccoli, komatsuna, green soybean, and radish contain LPAs and quantitated the LPA content using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). 7) Among the vegetables, cabbage leaf contains the largest amount of LPAs followed by broccoli, komatsuna, and green soybean. Interestingly, the amount of LPA homologues in cabbage leaf was in the order of LPA C 18:3 >LPA C 16:0 >LPA C 18:2 >LPA C 18:1 .…”

“…5) In plants, LPAs were identified in various parts such as leaf, seeds, and root but the content of LPAs in plants are variable. [6][7][8] Although it was unknown whether LPA receptor(s) are expressed in plant systems, Hecht et al first reported that ventricular zone gene-1, which is abundantly expressed in the ventricular zone during mammalian brain neurogenesis, encodes the LPA1 receptor. 9) In subsequent studies, six LPA receptor subtypes were further cloned on the surface of various cells and most organs also expressed endogenous LPA receptor subtypes.…”

Physiological Significance of Lysophospholipids that Act on the Lumen Side of Mammalian Lower Digestive Tracts

“…26) Recently, various types of vegetables including cabbage leaf have been demonstrated to contain significant amounts of LPA. 27) Cabbage leaf was the richest vegetable source of LPA, the major molecular species of which were α-linolenate (18 : 3)-containing species followed by palmitate (16 : 0)-, linoleate (18 : 2)-and oleate (18 : 1)-containing species in that order. 27) …”

Role of Phospholipids in Protection of the GI Mucosa

“…They also demonstrated by immunohistochemistry the presence of the LPA 2 receptor, the key G-protein coupled receptor involved in the anti-apoptotic response [35], on the luminal surface of rodent gastric epithelial cells (most likely surface mucous cells) and that aspirin-treatment markedly decreased this immunoreactivity. Furthermore, they reported that PA and LPA were present in the gastric contents of rats fed a normal diet, which was expected since these same phospholipids are present in soybean extracts, a usual constituent of rodent chow, and cruciferous vegetables such as cabbage [37]. Tanaka and associates also reported that the activity of phospholipase A 2 (PLA 2 ), which converts PA to LPA in the stomach, was enhanced by bile acids.…”