Alkaloids from Coptis chinensis root promote glucose uptake in C2C12 myotubes.
The root of Coptis chinensis Franch. (COCH) is regularly used for medicinal purposes, and has been prescribed alone or in combination with other traditional herbs for the treatment of diabetes. To investigate the effects of COCH on glucose utilization by skeletal muscles, we prepared an ethanol extract of COCH root (COCH-Et) partitioned with dichloromethane, n-butanol, and water and tested its effects on glucose uptake in differentiated C2C12 myotubes. We found that dichloromethane and n-butanol sub-fractions of COCH-Et promoted glucose uptake in differentiated C2C12 cells at 50 μg/mL. Further fractionation of these preparations by using column chromatography, analysis of their effects on glucose uptake and characterization using nuclear magnetic resonance, mass spectrometry, and thin layer chromatography helped identify two new alkaloids, 8,13-dioxocoptisine hydroxide (1) and coptisonine (2), together with eleven known compounds. These were isolated from the dichloromethane layer of COCH-Et. In particular, exposure of C2C12 cells to berberine (6) at 12.5 and 6.25 μg/mL for 24h resulted in significant promotion of glucose uptake. Coptisonine (2) and octadecyl caffeate (9) also stimulated glucose uptake at 25 and 50 μg/mL. These findings indicate that active constituents of COCH root may help alleviate hyperglycemia in diabetes by promoting glucose uptake by skeletal muscles.
Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
Te-Chun
TC
Yang
Graduate Institute of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
Hsin-Fan
HF
Chao
Department of Biotechnology, National Formosa University, Yunlin 632, Taiwan.
Li-Shian
LS
Shi
Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.
Tsu-Chung
TC
Chang
Graduate Institute of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan; Sinpharm Pharmaceutical Incorporated, I-Lan 269, Taiwan.
Hang-Ching
HC
Lin
Graduate Institute of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan. Electronic address: wlchang@ndmctsgh.edu.tw.
Wen-Liang
WL
Chang
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D039323:Coptis / Q000737:chemistry*; D003920:Diabetes Mellitus / Q000188:drug therapy; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification*; D051379:Mice; D018485:Muscle Fibers, Skeletal; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry
D000470:Alkaloids; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D005947:Glucose
8-Oxyberberine (PubChem CID 11066); Alkaloid; Berberine (PubChem CID 2353); Bicinchoninic acid (PubChem CID: 71068); C2C12 cells; Coptis chinensis; Corydaldine (PubChem CID 610097); Ethanol (PubChem CID: 702); Glucose uptake; KBr (PubChem CID: 253877); Noroxyhydrastinine (PubChem CID 89047); Octadecyl caffeate (PubChem CID 5320237); Skeletal muscle; [(14)C]-2-deoxy-glucose (PubChem CID: 6439681); β-Sitosterol (PubChem CID: 222284)