PMID- 38341069
OWN - NLM
STAT- MEDLINE
DCOM- 20240226
LR  - 20240226
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 753
DP  - 2024 Mar
TI  - Cinnamaldehyde attenuates TNF-alpha induced skeletal muscle loss in C2C12 myotubes 
      via regulation of protein synthesis, proteolysis, oxidative stress and 
      inflammation.
PG  - 109922
LID - S0003-9861(24)00041-9 [pii]
LID - 10.1016/j.abb.2024.109922 [doi]
AB  - Inflammation is the primary driver of skeletal muscle wasting, with oxidative 
      stress serving as both a major consequence and a contributor to its deleterious 
      effects. In this regard, regulation of both can efficiently prevent atrophy and 
      thus will increase the rate of survival [1]. With this idea, we hypothesize that 
      preincubation of Cinnamaldehyde (CNA), a known compound with anti-oxidative and 
      anti-inflammatory properties, may be able to prevent skeletal muscle loss. To 
      examine the same, C2C12 post-differentiated myotubes were treated with 25 ng/ml 
      Tumor necrosis factor-alpha (TNF-alpha) in the presence or absence of 50 muM CNA. The 
      data showed that TNF-alpha mediated myotube thinning and a lower fusion index were 
      prevented by CNA supplementation 4 h before TNF-alpha treatment. Moreover, a lower 
      level of ROS and thus maintained antioxidant defense system further underlines 
      the antioxidative function of CNA in atrophic conditions. CNA preincubation also 
      inhibited an increase in the level of inflammatory cytokines and thus led to a 
      lower level of inflammation even in the presence of TNF-alpha. With decreased 
      oxidative stress and inflammation by CNA, it was able to maintain the 
      intracellular level of injury markers (CK, LDH) and SDH activity of mitochondria. 
      In addition, CNA modulates all five proteolytic systems [cathepsin-L, UPS 
      (atrogin-1), calpain, LC3, beclin] simultaneously with an upregulation of 
      Akt/mTOR pathway, in turn, preserves the muscle-specific proteins (MHCf) from 
      degradation by TNF-alpha. Altogether, our study exhibits attenuation of muscle loss 
      and provides insight into the possible mechanism of action of CNA in curbing 
      TNF-alpha induced muscle loss, specifically its effect on proteolysis and protein 
      synthesis.
CI  - Copyright (c) 2024 Elsevier Inc. All rights reserved.
FAU - Kaur, Nirmaljeet
AU  - Kaur N
AD  - Skeletal Muscle Lab, Institute of Integrated & Honors Studies, Kurukshetra 
      University, Kurukshetra, Haryana, India.
FAU - Gupta, Prachi
AU  - Gupta P
AD  - Skeletal Muscle Lab, Institute of Integrated & Honors Studies, Kurukshetra 
      University, Kurukshetra, Haryana, India.
FAU - Dutt, Vikas
AU  - Dutt V
AD  - Skeletal Muscle Lab, Institute of Integrated & Honors Studies, Kurukshetra 
      University, Kurukshetra, Haryana, India.
FAU - Sharma, Onkar
AU  - Sharma O
AD  - Skeletal Muscle Lab, Institute of Integrated & Honors Studies, Kurukshetra 
      University, Kurukshetra, Haryana, India.
FAU - Gupta, Sanjeev
AU  - Gupta S
AD  - Skeletal Muscle Lab, Institute of Integrated & Honors Studies, Kurukshetra 
      University, Kurukshetra, Haryana, India.
FAU - Dua, Anita
AU  - Dua A
AD  - Skeletal Muscle Lab, Institute of Integrated & Honors Studies, Kurukshetra 
      University, Kurukshetra, Haryana, India.
FAU - Injeti, Elisha
AU  - Injeti E
AD  - Department of Pharmaceutical Sciences, Cedarville University, School of Pharmacy, 
      Cedarville, OH, USA.
FAU - Mittal, Ashwani
AU  - Mittal A
AD  - Skeletal Muscle Lab, Institute of Integrated & Honors Studies, Kurukshetra 
      University, Kurukshetra, Haryana, India. Electronic address: mittala@kuk.ac.in.
LA  - eng
PT  - Journal Article
DEP - 20240208
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - SR60A3XG0F (cinnamaldehyde)
RN  - 0 (Antioxidants)
RN  - 7864XYD3JJ (Acrolein)
SB  - IM
MH  - Humans
MH  - *Tumor Necrosis Factor-alpha/metabolism
MH  - Proteolysis
MH  - *Muscle, Skeletal/metabolism
MH  - Muscle Fibers, Skeletal/metabolism
MH  - Muscular Atrophy/chemically induced/drug therapy/metabolism
MH  - Oxidative Stress
MH  - Antioxidants/pharmacology/metabolism
MH  - Inflammation/metabolism
MH  - Acrolein/*analogs & derivatives
OTO - NOTNLM
OT  - CNA
OT  - Inflammation
OT  - Muscle loss
OT  - Oxidative stress
OT  - TNF-alpha
COIS- Declaration of competing interest All authors (NK, PG, VD, OS, SG, AD, EI, and 
      AM) declare that they have no conflicts of interest involving this work.
EDAT- 2024/02/11 07:42
MHDA- 2024/02/26 06:43
CRDT- 2024/02/10 19:18
PHST- 2023/09/11 00:00 [received]
PHST- 2024/01/10 00:00 [revised]
PHST- 2024/01/31 00:00 [accepted]
PHST- 2024/02/26 06:43 [medline]
PHST- 2024/02/11 07:42 [pubmed]
PHST- 2024/02/10 19:18 [entrez]
AID - S0003-9861(24)00041-9 [pii]
AID - 10.1016/j.abb.2024.109922 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2024 Mar;753:109922. doi: 10.1016/j.abb.2024.109922. Epub 
      2024 Feb 8.