Mulberry leaf ameliorates the expression profile of adipocytokines by inhibiting oxidative stress in white adipose tissue in db/db mice.
Previous study showed that mulberry (Morus Alba L.) leaf (ML) ameliorates atherosclerosis in apoE(-/-) mice. Although the adipocytokine dysregulation is an important risk factor for atherosclerotic cardiovascular disease, the effect of ML on metabolic disorders related to adipocytokine dysregulation and inflammation has not been studied. Therefore, we studied the effects of ML in metabolic disorders and examined the mechanisms by which ML ameliorates metabolic disorders in db/db mice. We treated db/db mice with ML, pioglitazone, or both for 12 weeks and found that ML decreased blood glucose and plasma triglyceride. Co-treatment with ML and pioglitazone showed additive effects compared with pioglitazone. Moreover, their co-treatment attenuated the body weight increase observed under the pioglitazone treatment. ML treatment also increased the expression of adiponectin, and decreased the expression of TNF-alpha, MCP-1, and macrophage markers in white adipose tissue (WAT). Furthermore, ML decreased lipid peroxides and the expression of NADPH oxidase subunits in WAT and liver. Their co-treatment enhanced these effects. Thus, ML ameliorates adipocytokine dysregulation at least in part through inhibiting oxidative stress in WAT of db/db mice, and that ML may be a basis for a pharmaceutical for the treatment of the metabolic syndrome as well as reducing adverse effects of pioglitazone.
Sugimoto
Masayuki
M
Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Japan.
Arai
Hidenori
H
Tamura
Yukinori
Y
Murayama
Toshinori
T
Khaengkhan
Parinda
P
Nishio
Takuya
T
Ono
Koh
K
Ariyasu
Hiroyuki
H
Akamizu
Takashi
T
Ueda
Yukihiko
Y
Kita
Toru
T
Harada
Shigeharu
S
Kamei
Kaeko
K
Yokode
Masayuki
M
D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D031625:Morus; D019255:NADPH Oxidases / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000077205:Pioglitazone; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves; D021122:Protein Subunits; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054392:Adipokines; D052242:Adiponectin; C499919:Adipoq protein, mouse; D000975:Antioxidants; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D021122:Protein Subunits; D045162:Thiazolidinediones; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D019255:NADPH Oxidases; D000077205:Pioglitazone