April 14, 2010
KANGWON-DO, South Korea According to Korean researchers, extracts from roasted licorice may be highly potent therapeutic agents for the prevention and treatment of mesangial fibrosis and glomerulosclerosis, which leads to diabetic nephropathy due to longstanding diabetes mellitus (Phytomedicine. April 9, 2010). Expansion of mesangial matrix around capillaries in the kidney glomeruli is a prominent feature of diabetic nephropathy; therefore researchers investigated whether licorice extracts inhibited mesangial cell (MC) proliferation and matrix accumulation induced by high glucose. Human renal MC were cultured in media containing 5.5mM of glucose plus 27.5mM of mannitol as an osmotic control, or 33mM of glucose for three days in the presence of water or ethanol extracts from raw licorice or roasted licorice.
Exposure of cells to high glucose caused significant increases in collagen IV secretion and connective tissue growth factor expression, which was appeased by roasted licorice (extract and water) at transcriptional levels. The inhibitory potency was high in the order of roasted licorice extract >/= roasted licorice in water >/= raw licorice extract >>raw licorice in water. Non-polar glycyrrhetic acid but not glycyrrhizin retarded high glucose-stimulated mesangial matrix deposition through diminishing connective tissue growth factor expression. In addition, roasted licorice (water and extract) but not raw licorice in water modulated membrane type matrix metalloproteinase-1 (MT-1 MMP) expression, MMP-2 activity and tissue inhibitor of MMP-2 (TIMP-2), which facilitated the degradation of mesangial matrix. Furthermore, the augmented expression of connective tissue growth factor and TIMP-2 in high glucose-exposed cells was mediated by Akt activation and TGF-beta/Smad signaling through PKCbeta2-responsive signaling pathways. However, high glucose-down-regulated MT-1 MMP expression was independent of activation of ERK1/2 and Akt when using their inhibitors of DB98059 (ERK1/2) and LY294002 (Akt) alone or in combination.
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