Discovery of pulmonary fibrosis inhibitor targeting TGF-β RI in <i>Polygonum cuspidatum</i> by high resolution mass spectrometry with in silico strategy

Huarong Xu; Jiameng Qu; Jian Wang; Kefei Han; Qing Li; Wenchuan Bi; Ran Liu

doi:10.1016/j.jpha.2020.05.007

Volume 12 Issue 6

Dec. 2022

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Huarong Xu, Jiameng Qu, Jian Wang, Kefei Han, Qing Li, Wenchuan Bi, Ran Liu. Discovery of pulmonary fibrosis inhibitor targeting TGF-β RI in Polygonum cuspidatum by high resolution mass spectrometry with in silico strategy[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 860-868. doi: 10.1016/j.jpha.2020.05.007

Citation:

Huarong Xu, Jiameng Qu, Jian Wang, Kefei Han, Qing Li, Wenchuan Bi, Ran Liu. Discovery of pulmonary fibrosis inhibitor targeting TGF-β RI in Polygonum cuspidatum by high resolution mass spectrometry with in silico strategy[J]. Journal of Pharmaceutical Analysis, 2022, 12(6): 860-868. doi: 10.1016/j.jpha.2020.05.007

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Discovery of pulmonary fibrosis inhibitor targeting TGF-β RI in Polygonum cuspidatum by high resolution mass spectrometry with in silico strategy

doi: 10.1016/j.jpha.2020.05.007

Huarong Xu^a,
Jiameng Qu^a,b,
Jian Wang^c,
Kefei Han^a,b,
Qing Li^a,
Wenchuan Bi^{d
,
,},
Ran Liu^{a
,
,}

a. National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China;
b. School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China;
c. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China;
d. Health Science Center Department of Pharmacy, Shenzhen University, Shenzhen, Guangdong, 518118, China

Funds:

This work was financially supported by the National Natural Science Foundation of China (Grant Nos.: 81703463 and 81603277), the National Key R&

D Program of China (Grant No.: U1508220), the Liaoning Distinguished Professor Project for Qing Li, and the Doctoral Scientific Research Foundation of Liaoning Province (Grant No.: 20170520199).

Received Date: Oct. 21, 2019
Accepted Date: May 20, 2020
Rev Recd Date: Apr. 27, 2020
Publish Date: Dec. 26, 2022

Abstract

Abstract

Pulmonary fibrosis (PF) is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2–3 years. The inhibition of transforming growth factor-β receptor type-I (TGF-β RI) by an appropriate drug may provide a promising strategy for the treatment of this disease. Polygonum cuspidatum (PC) is a well-known traditional Chinese herbal medicine which has an anti-PF effect. Accordingly, a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI. Based on this strategy, a total of 24 ingredients were identified. Then, absorption, distribution, metabolism, and excretion (ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour. Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors. Eventually, a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI, with an IC₅₀ of 2.211 μM in vitro. Furthermore, the complex formed through molecular docking was tested via molecular dynamics simulations, which revealed that resveratrol had strong interactions with residues of TGF-β RI. This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI. In addition, this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.
- Polygonum cuspidatum,
- Pulmonary fibrosis,
- TGF-β receptor type-I,
- Resveratrol,
- High resolution mass spectrometry,
- Molecular docking

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References(42)

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