PMID- 38464785
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240312
IS  - 2214-0883 (Electronic)
IS  - 2095-1779 (Print)
IS  - 2214-0883 (Linking)
VI  - 14
IP  - 2
DP  - 2024 Feb
TI  - Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis 
      using (13)C metabolic flux analysis.
PG  - 244-258
LID - 10.1016/j.jpha.2023.09.008 [doi]
AB  - Evidence indicates that metabolic reprogramming characterized by the changes in 
      cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis 
      (PF). It is considered as a promising therapeutic target anti-PF. The 
      well-documented against PF properties of Tanshinone IIA (Tan IIA) have been 
      primarily attributed to its antioxidant and anti-inflammatory potency. Emerging 
      evidence suggests that Tan IIA may target energy metabolism pathways, including 
      glycolysis and tricarboxylic acid (TCA) cycle. However, the detailed and advanced 
      mechanisms underlying the anti-PF activities remain obscure. In this study, we 
      applied [U-(13)C]-glucose metabolic flux analysis (MFA) to examine metabolism 
      flux disruption and modulation nodes of Tan IIA in PF. We identified that Tan IIA 
      inhibited the glycolysis and TCA flux, thereby suppressing the production of 
      transforming growth factor-beta1 (TGF-beta1)-dependent extracellular matrix and the 
      differentiation and proliferation of myofibroblasts in vitro. We further revealed 
      that Tan IIA inhibited the expression of key metabolic enzyme hexokinase 2 (HK2) 
      by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian 
      target of rapamycin (mTOR)/hypoxia-inducible factor 1alpha (HIF-1alpha) pathway 
      activities, which decreased the accumulation of abnormal metabolites. Notably, we 
      demonstrated that Tan IIA inhibited ATP citrate lyase (ACLY) activity, which 
      reduced the collagen synthesis pathway caused by cytosol citrate consumption. 
      Further, these results were validated in a mouse model of bleomycin-induced PF. 
      This study was novel in exploring the mechanism of the occurrence and development 
      of Tan IIA in treating PF using (13)C-MFA technology. It provided a novel 
      understanding of the mechanism of Tan IIA against PF from the perspective of 
      metabolic reprogramming.
CI  - (c) 2023 The Author(s).
FAU - Shan, Baixi
AU  - Shan B
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing, 210009, China.
AD  - Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China 
      Pharmaceutical University, Nanjing, 210009, China.
FAU - Zhou, Haoyan
AU  - Zhou H
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing, 210009, China.
AD  - Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China 
      Pharmaceutical University, Nanjing, 210009, China.
FAU - Guo, Congying
AU  - Guo C
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing, 210009, China.
AD  - Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China 
      Pharmaceutical University, Nanjing, 210009, China.
FAU - Liu, Xiaolu
AU  - Liu X
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing, 210009, China.
AD  - Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China 
      Pharmaceutical University, Nanjing, 210009, China.
FAU - Wu, Mingyu
AU  - Wu M
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing, 210009, China.
AD  - Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China 
      Pharmaceutical University, Nanjing, 210009, China.
FAU - Zhai, Rao
AU  - Zhai R
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing, 210009, China.
AD  - Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China 
      Pharmaceutical University, Nanjing, 210009, China.
FAU - Chen, Jun
AU  - Chen J
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, 
      Nanjing, 210009, China.
AD  - Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China 
      Pharmaceutical University, Nanjing, 210009, China.
LA  - eng
PT  - Journal Article
DEP - 20230921
PL  - China
TA  - J Pharm Anal
JT  - Journal of pharmaceutical analysis
JID - 101579451
PMC - PMC10921327
OTO - NOTNLM
OT  - 13C-metabolic flux analysis
OT  - Metabolic reprogramming
OT  - Pulmonary fibrosis
OT  - Tanshinone IIA
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2024/03/11 06:43
MHDA- 2024/03/11 06:44
PMCR- 2023/09/21
CRDT- 2024/03/11 04:41
PHST- 2023/05/26 00:00 [received]
PHST- 2023/09/06 00:00 [revised]
PHST- 2023/09/18 00:00 [accepted]
PHST- 2024/03/11 06:44 [medline]
PHST- 2024/03/11 06:43 [pubmed]
PHST- 2024/03/11 04:41 [entrez]
PHST- 2023/09/21 00:00 [pmc-release]
AID - S2095-1779(23)00246-0 [pii]
AID - 10.1016/j.jpha.2023.09.008 [doi]
PST - ppublish
SO  - J Pharm Anal. 2024 Feb;14(2):244-258. doi: 10.1016/j.jpha.2023.09.008. Epub 2023 
      Sep 21.