title: The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6J mice.
abstract: BACKGROUND
  Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from M. officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy.
  
  
  METHODS
  ALS-L1023 was prepared by a two-step organic solvent fractionation from M. officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches.
  
  
  RESULTS
  ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice.
  
  
  CONCLUSIONS
  These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 302-729, Republic of Korea.
authors.forename: Sangee
authors.initials: S
authors.lastname: Woo
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 302-729, Republic of Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 302-729, Republic of Korea.
authors.forename: Jeongjun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 302-729, Republic of Korea.
authors.forename: Yeonhee
authors.initials: Y
authors.lastname: Hong
authors.affiliation: AngioLab, Inc., Daejeon 305-509, Republic of Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Formula Sciences, College of Korean Medicine, Dongeui University, Busan 614-052, Republic of Korea.
authors.forename: Soon Shik
authors.initials: SS
authors.lastname: Shin
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 302-729, Republic of Korea. Electronic address: yoon60@mokwon.ac.kr.
authors.forename: Michung
authors.initials: M
authors.lastname: Yoon
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006984:Hypertrophy / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D031334:Melissa / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C000608553:ALS-L1023; D043925:Angiogenesis Inducing Agents; D010936:Plant Extracts; D012333:RNA, Messenger
keywords: Adipogenesis; Angiogenesis; Anti-angiogenic plant; MMP; Melissa officinalis; Obesity