Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using <sup>13</sup>C metabolic flux analysis

Baixi Shan; Haoyan Zhou; Congying Guo; Xiaolu Liu; Mingyu Wu; Rao Zhai; Jun Chen

doi:10.1016/j.jpha.2023.09.008

Volume 14 Issue 2

Feb. 2024

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Baixi Shan, Haoyan Zhou, Congying Guo, Xiaolu Liu, Mingyu Wu, Rao Zhai, Jun Chen. Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using 13C metabolic flux analysis[J]. Journal of Pharmaceutical Analysis, 2024, 14(2): 244-258. doi: 10.1016/j.jpha.2023.09.008

Citation:

Baixi Shan, Haoyan Zhou, Congying Guo, Xiaolu Liu, Mingyu Wu, Rao Zhai, Jun Chen. Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using ¹³C metabolic flux analysis[J]. Journal of Pharmaceutical Analysis, 2024, 14(2): 244-258. doi: 10.1016/j.jpha.2023.09.008

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Tanshinone IIA ameliorates energy metabolism dysfunction of pulmonary fibrosis using ¹³C metabolic flux analysis

doi: 10.1016/j.jpha.2023.09.008

Baixi Shan^a,b,
Haoyan Zhou^a,b,
Congying Guo^a,b,
Xiaolu Liu^a,b,
Mingyu Wu^a,b,
Rao Zhai^a,b,
Jun Chen^{a,b
,
,}

a. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China;
b. Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China

Funds:

This work was financially supported by the National Natural Science Foundation of China (Grant No.: 82174100). The authors thank Nian Wang and Zi-Yuan Wang for technical support from the Center for Analysis and Testing of China Pharmaceutical University.

Received Date: May 26, 2023
Accepted Date: Sep. 18, 2023
Rev Recd Date: Sep. 06, 2023
Publish Date: Feb. 29, 2024

Abstract

Abstract

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-¹³C]-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-β1 (TGF-β1)-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 1α (HIF-1α) 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 ¹³C-MFA technology. It provided a novel understanding of the mechanism of Tan IIA against PF from the perspective of metabolic reprogramming.
- Pulmonary fibrosis,
- Tanshinone IIA,
- ¹³C-metabolic flux analysis,
- Metabolic reprogramming

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References(49)

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