PMID- 32347284
OWN - NLM
STAT- MEDLINE
DCOM- 20210720
LR  - 20210720
IS  - 1477-0539 (Electronic)
IS  - 1477-0520 (Linking)
VI  - 18
IP  - 18
DP  - 2020 May 13
TI  - Synthesis of disaccharide modified berberine derivatives and their anti-diabetic 
      investigation in zebrafish using a fluorescence-based technology.
PG  - 3563-3574
LID - 10.1039/d0ob00327a [doi]
AB  - Berberine is a naturally occurring isoquinoline alkaloid and has been used as an 
      important functional food additive in China due to its various pharmacological 
      activities. Berberine exhibits great potential for developing anti-diabetic 
      agents against type 2 diabetes mellitus (T2DM), as it can reduce the blood 
      glucose level in many animal models. However, the low anti-diabetic activity and 
      poor bioavailability of berberine (below 5%) by oral administration significantly 
      limit its practical applications. To solve these problems, this article focuses 
      on the structural modification of berberine using some disaccharide groups, 
      because the carbohydrate moiety has been proved to improve the bioavailability 
      and enhance the receptor-binding affinity of drugs. Anti-diabetic investigation 
      of the synthesized compounds was performed in a zebrafish model using a 
      fluorescently labelled glucose analog 
      2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a 
      glucose tracker. The results indicated that the modification of berberine with 
      carbohydrate groups could give derivatives with improved anti-diabetic activity, 
      in particular the diglucose modified berberine derivative 1 which could 
      dramatically promote the uptake of 2-NBDG in both zebrafish larvae and their eyes 
      even at very low concentrations. Furthermore, the fluorescence-based 
      anti-diabetic investigation method in zebrafish shows great potential for 
      anti-diabetic drug screening.
FAU - Wang, Lizhen
AU  - Wang L
AD  - Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 
      Jinan 250014, Shandong Province, China. wlzh1106@126.com liukechun2000@163.com.
FAU - Kong, Haotian
AU  - Kong H
FAU - Jin, Meng
AU  - Jin M
FAU - Li, Xiaobin
AU  - Li X
FAU - Stoika, Rostyslav
AU  - Stoika R
FAU - Lin, Houwen
AU  - Lin H
FAU - Liu, Kechun
AU  - Liu K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Org Biomol Chem
JT  - Organic & biomolecular chemistry
JID - 101154995
RN  - 0 (Blood Glucose)
RN  - 0 (Disaccharides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0I8Y3P32UF (Berberine)
SB  - IM
MH  - Animals
MH  - Berberine/chemical synthesis/chemistry/*pharmacology
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Disaccharides/chemistry/*pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - *Fluorescence
MH  - Hypoglycemic Agents/chemical synthesis/chemistry/*pharmacology
MH  - Molecular Structure
MH  - Zebrafish
EDAT- 2020/04/30 06:00
MHDA- 2021/07/21 06:00
CRDT- 2020/04/30 06:00
PHST- 2020/04/30 06:00 [pubmed]
PHST- 2021/07/21 06:00 [medline]
PHST- 2020/04/30 06:00 [entrez]
AID - 10.1039/d0ob00327a [doi]
PST - ppublish
SO  - Org Biomol Chem. 2020 May 13;18(18):3563-3574. doi: 10.1039/d0ob00327a.