| 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models. | |
| | |
MedLine Citation:
|
PMID: 20663675 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The clinical use of the natural alkaloid berberine (BBR) as an antidiabetic reagent is limited by its poor bioavailability. Our previous work demonstrated that dihydroberberine (dhBBR) has enhanced bioavailability and in vivo efficacy compared with berberine. Here we synthesized the 8,8-dimethyldihydroberberine (Di-Me) with improved stability, and bioavailability over dhBBR. Similar to BBR and dhBBR, Di-Me inhibited mitochondria respiration, increased AMP:ATP ratio, activated AMPK and stimulated glucose uptake in L6 myotubes. In diet-induced obese (DIO) mice, Di-Me counteracted the increased adiposity, tissue triglyceride accumulation and insulin resistance, and improved glucose tolerance at a dosage of 15mg/kg. Administered to db/db mice with a dosage of 50mg/kg, Di-Me effectively reduced random fed and fasting blood glucose, improved glucose tolerance, alleviated insulin resistance and reduced plasma triglycerides, with better efficacy than dhBBR at the same dosage. Our work highlights the importance of dihydroberberine analogs as potential therapeutic reagents for type 2 diabetes treatment. |
| | |
Authors:
|
Zhe Cheng; An-Feng Chen; Fang Wu; Li Sheng; Han-Kun Zhang; Min Gu; Yuan-Yuan Li; Li-Na Zhang; Li-Hong Hu; Jing-Ya Li; Jia Li |
Related Documents
:
|
17129725 - Design and synthesis of a novel class of dual ppargamma/delta agonists. 6478245 - Glucose utilization by the mouse brain: influence of age and diabetes. 15922295 - Increased expression of nad(p)h oxidase in islets of animal models of type 2 diabetes a... 3013555 - Genetic predisposition to diabetes mellitus is associated with impaired humoral immunit... 10447755 - Endogenous interleukin-12 only plays a key pathogenetic role in non-obese diabetic mous... 16022095 - A risk analysis of continuous ambulatory peritoneal dialysis-related peritonitis. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-01 |
Journal Detail:
|
Title: Bioorganic & medicinal chemistry Volume: 18 ISSN: 1464-3391 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-09 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
|
Languages: eng Pagination: 5915-24 Citation Subset: IM |
Copyright Information:
|
Copyright 2010. Published by Elsevier Ltd. |
Affiliation:
|
National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Berberine / analogs & derivatives*, chemistry, pharmacokinetics, pharmacology, therapeutic use Diabetes Mellitus / drug therapy* Electron Transport / drug effects Glucose / metabolism Humans Hypoglycemic Agents / chemistry, pharmacokinetics*, pharmacology, therapeutic use* Male Mice Mice, Inbred C57BL Mitochondria / drug effects Obesity / drug therapy* Rats Rats, Sprague-Dawley Solubility |
| Chemical | |
Reg. No./Substance:
|
0/Hypoglycemic Agents; 2086-83-1/Berberine; 483-15-8/dihydroberberine; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Phenolic constituents isolated from Fragaria ananassa Duch. inhibit antigen-stimulated degranulation...
Next Document: Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates.