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. 2025 Jun;398(6):7251-7262.
doi: 10.1007/s00210-024-03755-8. Epub 2024 Dec 27.

Phytochemical investigation of Jie-Geng-Tang and regulatory role in the TNF-α pathway in mitigating pulmonary fibrosis using UPLC-Q-TOF/MS

Bingxin Li  1 , Ruining Zhao  1 , Xiaojie Jiang  1 , Chang Liu  1 , Yun Ma  1 , Haijun Zhang  2
Affiliations

Phytochemical investigation of Jie-Geng-Tang and regulatory role in the TNF-α pathway in mitigating pulmonary fibrosis using UPLC-Q-TOF/MS

Bingxin Li et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun.

Abstract

Jie-Geng-Tang (JGT), composed of Platycodon grandiflorus (Jacq.) A. DC and Glycyrrhiza uralensis Fisch, is widely used in traditional Chinese medicine for its potential effects in preventing pulmonary fibrosis (PF). This study systematically explored the effects of JGT's water and 70% EtOH extracts in bleomycin (BLM)-induced PF models. In vitro, the 70% EtOH extract significantly reversed BLM-induced reductions in cell viability and apoptosis, whereas the water extract had limited impact. In vivo, the EtOH extract markedly reduced fibrosis markers, such as α-SMA and collagen-I, alleviating lung tissue damage and collagen deposition. UPLC-Q-TOF/MS analysis revealed that the EtOH extract contained a higher abundance of flavonoids compared to the water extract. Through network pharmacology analysis of the EtOH extract, four key flavonoids-apigenin, kaempferol, kaempferol 3-glucuronoside, and quercetin-were identified as crucial compounds. These flavonoids were found to reverse BLM-induced cell viability loss, with apigenin showing the most pronounced effect by modulating the TNF-α signaling pathway and inhibiting caspase-3 activation. Apigenin, as a primary active component derived from JGT, holds significant potential as a preventive agent against pulmonary fibrosis.

Keywords: Apigenin; Apoptosis; Jie-Geng-Tang; TNF-α pathway.

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Conflict of interest statement

Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of The Liaoning Changsheng Biotechnology (CSE20201017). Consent to participate: Not applicable Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Research involving animals: Male C57BL/6 mice (5–7 weeks old) were obtained from Liaoning Changsheng Biotechnology (Approval No. SCXK(Liao)2020-00001). The mice were randomly assigned into five groups. Following 1 week of acclimatization, mice in the drug treatment groups were administered the extract or PFD orally for three consecutive days. Subsequently, mice in the BLM groups were intratracheally instilled with 5 mg/kg BLM, while the control group received an equivalent volume of saline. Three weeks post-treatment, the mice were euthanized for sample collection and analysis.

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