title: Wogonin ameliorates hyperglycemia and dyslipidemia via PPARα activation in db/db mice.
abstract: OBJECTIVE
  Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis Gerogi. We evaluated the therapeutic effects of wogonin using db/db mice.
  
  
  METHODS
  Mice received wogonin or vehicle by oral gavage for 2 weeks. Blood glucose, insulin, and cholesterol levels were measured, and liver morphology was observed with histopathological analysis. The mRNA expression levels of PPARα, PPARγ, and adiponectin in the liver and white adipose tissue (WAT) were determined by real-time PCR. Immunoblotting for AMPK and PPARγ, and adipocyte differentiation were investigated in vitro using 3T3-L1 cells. A luciferase assay was used to measure PPARα and PPARγ binding activity.
  
  
  RESULTS
  The wogonin group showed decreased weight gain without a change in food intake and improved glucose tolerance. Serum insulin and cholesterol levels in the wogonin group were significantly decreased compared to those in the control group. The wogonin group also showed less accumulation of lipid droplets and glycogen in the liver. PPARα and PPARγ expression levels in the liver and WAT and adiponectin expression level in WAT in the wogonin group were higher than those in the control group. In 3T3-L1 cells, wogonin was shown to stimulate AMPK activation in a dose-dependent manner. The presence of wogonin did not affect adipocyte differentiation or PPARγ protein level during adipogenesis. Notably, wogonin enhanced PPARα but not PPARγ transactivation.
  
  
  CONCLUSIONS
  These indicate that wogonin may have beneficial effects on glucose and lipid metabolism related to enhanced PPARα and adiponectin expression via AMPK activation. Importantly, wogonin did not cause deleterious effects, such as weight gain and fatty liver. Wogonin might be a useful therapeutic agent to treat type 2 diabetes.
authors.affiliation: Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Bak
authors.affiliation: Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea; Department of Applied Life Science, Yonsei University Graduate School, Seoul, Republic of Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: Jinmoon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Applied Life Science, Yonsei University Graduate School, Seoul, Republic of Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: Yun Hui
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea; Department of Applied Life Science, Yonsei University Graduate School, Seoul, Republic of Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea; Department of Applied Life Science, Yonsei University Graduate School, Seoul, Republic of Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Lee
authors.affiliation: Department of Clinical Science, Semyung University, Jecheon, Republic of Korea.
authors.forename: Gye-Hyeong
authors.initials: GH
authors.lastname: Woo
authors.affiliation: Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Republic of Korea; Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea; Department of Applied Life Science, Yonsei University Graduate School, Seoul, Republic of Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea.
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Cha
authors.affiliation: Research Center for Orofacial Hard Tissue Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea; Department of Applied Life Science, Yonsei University Graduate School, Seoul, Republic of Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Republic of Korea. Electronic address: yu618@yuhs.ac.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects; D052242:Adiponectin / Q000097:blood / Q000235:genetics; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D050171:Dyslipidemias / Q000188:drug therapy*; D044950:Flavanones / Q000494:pharmacology*; D015870:Gene Expression; D006943:Hyperglycemia / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D044950:Flavanones; D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases; C085514:wogonin
keywords: Hyperglycemia; Hyperlipidemia; Insulin; PPAR; Type 2 diabetes; Wogonin