title: Combined treatment of betulinic acid, a PTP1B inhibitor, with Orthosiphon stamineus extract decreases body weight in high-fat-fed mice.
abstract: Leptin resistance is a common feature of obesity and is accompanied by hyperleptinemia. Although leptin sensitizers improve leptin resistance, they also decrease plasma leptin levels that attenuate the leptin-associated antiobesity effect. We hypothesized that the combinational treatment of leptin sensitizer and endogenous leptin expression stimulant would synergistically induce an antiobesity effect in high-fat-fed obese animals. Betulinic acid (BA) isolated from Saussurea lappa suppressed the hypothalamic protein tyrosine phosphatase 1B in mice and enhanced the antiobesity effect of leptin in obese rats. Ethanol extract of Orthosiphon stamineus (OS) induced leptin expressions in both 3T3-L1 adipocytes and mice in a dose-dependent manner. To evaluate our hypothesis, we treated obese mice induced by 6 weeks of high-fat-diet feeding with BA and OS for 2 weeks. Although BA or OS alone did not decrease body weight in obese mice, the combinational treatment of BA and OS decreased body weight significantly compared to either BA- or OS-treated obese mice. These results suggest that combinational treatment of BA and OS would be effective for the treatment of obesity.
authors.affiliation: Department of Physiology, School of Medicine, Yeungnam University, Daegu, Korea.
authors.forename: Yoon-Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Won
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Kim
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Yong-Woon
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D041681:NIH 3T3 Cells; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D031342:Orthosiphon / Q000737:chemistry*; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000008:administration & dosage*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D030441:Saussurea / Q000737:chemistry*; D014315:Triterpenes / Q000008:administration & dosage*; D000094062:Betulinic Acid
chemical_list: D004041:Dietary Fats; D004791:Enzyme Inhibitors; D020738:Leptin; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D000094062:Betulinic Acid