PMID- 31787729
OWN - NLM
STAT- MEDLINE
DCOM- 20200804
LR  - 20211204
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 43
IP  - 2
DP  - 2020 Feb 1
TI  - To Elucidate the Inhibition of Excessive Autophagy of Rhodiola crenulata on 
      Exhaustive Exercise-Induced Skeletal Muscle Injury by Combined Network 
      Pharmacology and Molecular Docking.
PG  - 296-305
LID - 10.1248/bpb.b19-00627 [doi]
AB  - Autophagy can remodel skeletal muscle in response to exercise. However, excessive 
      autophagy can have adverse effects on skeletal muscle. Although Rhodiola 
      crenulata (R. crenulata) is thought to regulate autophagy, its active ingredients 
      and mechanisms of action remain unclear. In this study, molecular docking and 
      network pharmacology were used to screen for autophagy-related targets of R. 
      crenulata. Subsequently, protein-protein interaction (PPI) analysis was used to 
      find the relationships between the inverse docking targets and autophagy-related 
      targets and therefore highlight the key targets. And then the Database for 
      Annotation, Visualization, and Integrated Discovery (DAVID) database was 
      recruited to explain the functions and enrichment pathways of the target 
      proteins. Finally, the potential targets were validated by immunohistochemistry 
      of a mouse model of exhaustive exercise-induced skeletal muscle injury. We found 
      a network of 15 major constituents of R. crenulata with 30 autophagy-related and 
      105 inverse-docking targets by molecular docking and network pharmacology. The 
      results of PPI analysis indicated that 16 inverse-docking targets interacted 8 
      autophagy-related proteins. Further pathway analysis showed that R. crenulata 
      could regulate exercise-induced skeletal muscle autophagy through mammalian 
      target of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Forkhead box 
      protein O (FoxO). The results of our animal experiments indicated that R. 
      crenulata could suppress the expression of Ubiquitin-like protein ATG12 (ATG12), 
      Beclin-1 (BECN1), and Serine/threonine-protein kinase ULK1 (ULK1), while 
      increasing the expression of MTOR, NAD-dependent protein deacetylase sirtuin-1 
      (SIRT1), and Microtubule-associated protein tau (MAPT). In conclusion, this study 
      demonstrated that R. crenulata may protect skeletal muscle injury induced by 
      exhaustive exercise via regulating the mTOR, AMPK, and FoxO singling pathway.
FAU - Li, Xuanhao
AU  - Li X
AD  - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University 
      of Traditional Chinese Medicine.
FAU - Hou, Ya
AU  - Hou Y
AD  - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University 
      of Traditional Chinese Medicine.
FAU - Wang, Xiaobo
AU  - Wang X
AD  - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University 
      of Traditional Chinese Medicine.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University 
      of Traditional Chinese Medicine.
FAU - Meng, Xianli
AU  - Meng X
AD  - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University 
      of Traditional Chinese Medicine.
FAU - Hu, Yao
AU  - Hu Y
AD  - Interdisciplinary Laboratory of Exercise and Medicine, Chengdu University of 
      Traditional Chinese Medicine.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University 
      of Traditional Chinese Medicine.
LA  - eng
PT  - Journal Article
DEP - 20191129
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Atg12 protein, mouse)
RN  - 0 (Autophagy-Related Protein 12)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, mouse)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (MAPT protein, human)
RN  - 0 (Plant Extracts)
RN  - 0 (tau Proteins)
RN  - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ulk1 protein, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein 12/metabolism
MH  - Autophagy-Related Protein-1 Homolog
MH  - Beclin-1
MH  - Forkhead Box Protein O1
MH  - Male
MH  - Mice
MH  - *Molecular Docking Simulation
MH  - Muscle, Skeletal/*drug effects/metabolism
MH  - Plant Extracts/*chemistry/genetics/*pharmacology
MH  - *Rhodiola
MH  - Sirtuin 1
MH  - TOR Serine-Threonine Kinases
MH  - tau Proteins
OTO - NOTNLM
OT  - Rhodiola crenulata
OT  - autophagy
OT  - immunohistochemistry
OT  - molecular docking
OT  - network pharmacology
EDAT- 2019/12/04 06:00
MHDA- 2020/08/05 06:00
CRDT- 2019/12/03 06:00
PHST- 2019/12/04 06:00 [pubmed]
PHST- 2020/08/05 06:00 [medline]
PHST- 2019/12/03 06:00 [entrez]
AID - 10.1248/bpb.b19-00627 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2020 Feb 1;43(2):296-305. doi: 10.1248/bpb.b19-00627. Epub 2019 
      Nov 29.