Tadehaginosides A-J, Phenylpropanoid Glucosides from Tadehagi triquetrum, Enhance Glucose Uptake via the Upregulation of PPARγ and GLUT-4 in C2C12 Myotubes.
Ten new phenylpropanoid glucosides, tadehaginosides A-J (1-10), and the known compound tadehaginoside (11) were obtained from Tadehagi triquetrum. These phenylpropanoid glucosides were structurally characterized through extensive physical and chemical analyses. Compounds 1 and 2 represent the first set of dimeric derivatives of tadehaginoside with an unusual bicyclo[2.2.2]octene skeleton, whereas compounds 3 and 4 contain a unique cyclobutane basic core in their carbon scaffolds. The effects of these compounds on glucose uptake in C2C12 myotubes were evaluated. Compounds 3-11, particularly 4, significantly increased the basal and insulin-elicited glucose uptake. The results from molecular docking, luciferase analyses, and ELISA indicated that the increased glucose uptake may be due to increases in peroxisome proliferator-activated receptor γ (PPARγ) activity and glucose transporter-4 (GLUT-4) expression. These results indicate that the isolated phenylpropanoid glucosides, particularly compound 4, have the potential to be developed into antidiabetic compounds.
School of Pharmaceutical Science, Hainan Medical University , Hainan 571199, People's Republic of China.
Xiaopo
X
Zhang
School of Pharmaceutical Science, Hainan Medical University , Hainan 571199, People's Republic of China.
Changyu
C
Chen
School of Pharmaceutical Science, Hainan Medical University , Hainan 571199, People's Republic of China.
Yonghui
Y
Li
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100193, People's Republic of China.
Deli
D
Chen
School of Pharmaceutical Science, Hainan Medical University , Hainan 571199, People's Republic of China.
Lin
L
Dong
School of Pharmaceutical Science, Hainan Medical University , Hainan 571199, People's Republic of China.
Wei
W
Na
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100193, People's Republic of China.
Chongming
C
Wu
School of Pharmaceutical Science, Hainan Medical University , Hainan 571199, People's Republic of China.
Junqing
J
Zhang
School of Pharmaceutical Science, Hainan Medical University , Hainan 571199, People's Republic of China.
Youbin
Y
Li
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003373:Coumaric Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007887:Fabaceae / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D047495:PPAR gamma / Q000378:metabolism*; D015854:Up-Regulation
D003373:Coumaric Acids; D004365:Drugs, Chinese Herbal; D051275:Glucose Transporter Type 4; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; C000595638:tadehaginoside; D005947:Glucose