PMID- 33900301
OWN - NLM
STAT- MEDLINE
DCOM- 20210602
LR  - 20210602
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 12
IP  - 8
DP  - 2021 Apr 21
TI  - Zanthoxylum alkylamides ameliorate protein metabolism in type 2 diabetes mellitus 
      rats by regulating multiple signaling pathways.
PG  - 3740-3753
LID - 10.1039/d0fo02695f [doi]
AB  - Type 2 diabetes mellitus (T2DM) can easily induce insulin resistance (IR) in 
      skeletal muscle, causing protein metabolism disorder and inflammation. The 
      present study aimed to investigate whether Zanthoxylum alkylamides (ZA) could 
      ameliorate T2DM through regulating protein metabolism disorder by using a rat 
      model of T2DM. The predominant bioactive constituents found in ZA were 
      hydroxyl-alpha-sanshool, hydroxyl-beta-sanshool and hydroxyl-gamma-sanshool. The results 
      showed that ZA improved a series of biochemical indices associated with protein 
      metabolism and inflammation in T2DM rats. Our mechanistic finding indicated that 
      ZA promoted protein anabolism in T2DM rats by up-regulating the phosphoinositide 
      3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) 
      signaling pathway. ZA also promoted glucose transportation in skeletal muscle to 
      ameliorate skeletal muscle IR and energy metabolism through regulating the 
      AMP-activated protein kinase (AMPK) signaling pathway. Moreover, ZA inhibited 
      protein degradation and improved protein catabolism disorder in T2DM rats by 
      down-regulating the PI3K/Akt/forkhead box O (FoxO) signaling pathway, and ZA 
      further ameliorated inflammation to inhibit protein catabolism via regulating the 
      tumor necrosis factor alpha (TNF-alpha)/nuclear factor kappaB (NF-kappaB) pathway in the skeletal 
      muscle of T2DM rats. Collectively, the ameliorating effect of ZA on protein 
      metabolism disorder in T2DM rats was the common result of regulating multiple 
      signaling pathways. ZA decreased skeletal muscle IR to promote protein anabolism 
      and inhibit protein catabolism for improving protein metabolism disorder, thus 
      ultimately ameliorating T2DM. In sum, our findings demonstrated that ZA treatment 
      could effectively ameliorate T2DM through improving protein metabolism, providing 
      a new treatment target for T2DM.
FAU - Wei, Xunyu
AU  - Wei X
AD  - College of Food Science, Southwest University, 2 Tiansheng Road, Beibei, 
      Chongqing 400715, PR China. kanjianquan@163.com.
FAU - Yang, Bing
AU  - Yang B
FAU - Chen, Xuhui
AU  - Chen X
FAU - Wen, Leyan
AU  - Wen L
FAU - Kan, Jianquan
AU  - Kan J
LA  - eng
PT  - Journal Article
DEP - 20210407
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Polyunsaturated Alkamides)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*prevention & control
MH  - Disease Models, Animal
MH  - Polyunsaturated Alkamides/*administration & dosage/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - *Zanthoxylum
EDAT- 2021/04/27 06:00
MHDA- 2021/06/03 06:00
CRDT- 2021/04/26 12:18
PHST- 2021/04/27 06:00 [pubmed]
PHST- 2021/06/03 06:00 [medline]
PHST- 2021/04/26 12:18 [entrez]
AID - 10.1039/d0fo02695f [doi]
PST - ppublish
SO  - Food Funct. 2021 Apr 21;12(8):3740-3753. doi: 10.1039/d0fo02695f. Epub 2021 Apr 
      7.