title: Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice.
abstract: The purpose of this study was to assess the effects of low-dose ursolic acid (UA) on glycemic regulation and immune responses in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Diabetic mice were supplemented with two different doses of UA (0.01 and 0.05%, w/w) or metformin (0.5%, w/w) for 4 weeks. Compared with the untreated diabetic group, UA and metformin significantly improved blood glucose, glycosylated hemoglobin, glucose tolerance, insulin tolerance and plasma leptin levels as well as aminotransferase activity. The plasma and pancreatic insulin concentrations were significantly higher in both UA groups than in the untreated diabetic group. Supplementation with metformin increased the pancreatic insulin level without a change in the plasma insulin level. The relative thymus weights were lower in the untreated diabetic group compared to the non-diabetic group; however, the UA or metformin group had significantly improved thymus weights. Mice receiving UA or metformin supplementation had increased CD4(+)CD8(+) subpopulations in the thymus compared to the untreated diabetic mice. Concanavalin A-stimulated splenic T-lymphocyte proliferation and single-positive (CD4(+) and CD8(+)) subpopulations were significantly higher in the UA-supplemented diabetic groups than in the untreated diabetic group, but lipopolysaccharide-stimulated B-lymphocyte proliferation and the CD19(+) subpopulation were not significantly different among the groups. In the STZ/NA-induced diabetic mice, metformin increased the splenic T-lymphocyte CD4(+) and CD8(+) cell numbers without any change in T-lymphocyte proliferation. Both doses of UA lowered splenic IL-6 levels, whereas metformin increased IFN-γ, IL-6 and TNF-α levels compared to the untreated diabetic mice. These results suggest that low-dose UA may be used as a hypoglycemic agent and immune modulator in non-obese type 2 diabetic mice.
authors.affiliation: Department of Food and Nutrition, Sunchon National University, Suncheon 540-742, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Yee
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Kim
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kwon
authors.forename: Kwon-Il
authors.initials: KI
authors.lastname: Seo
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
mesh_terms: D000818:Animals; D001284:Atrophy / Q000188:drug therapy; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009536:Niacinamide / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology*; D000637:Transaminases / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D000097245:Ursolic Acid
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D006442:Glycated Hemoglobin; D007328:Insulin; D020738:Leptin; D009536:Niacinamide; D000637:Transaminases; D014315:Triterpenes; D000097245:Ursolic Acid