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Differently Regulated Metabolites by Qingfei Paidu Decoction

ABSTRACT:

Ethnopharmacological relevance: Qingfei Paidu decoction (QFPDD), a traditional Chinese medicine (TCM) formula derived from the TCM theory of “lung pathogen-dispersing and toxin-eliminating”, holds considerable ethnopharmacological importance in the treatment of viral pneumonia. Our study revealed that QFPDD achieves its therapeutic effects through a novel-miR-89-mediated antiviral pathway and a glycyrrhetinic acid (GA)-mediated anti-inflammatory pathway, thereby establishing a connection between traditional therapeutic knowledge and modern mechanistic understanding. These findings underscore the characteristic “multi-components, multi-targets, and synergistic effects” value of ethnomedicine.

Aim of the study: To investigate the multiple action mechanisms of QFPDD in the treatment of viral pneumonia.

Materials and methods: Firstly, the multi-components of QFPDD were screened by miRNA profiling and metabolomic analysis.

rats were administered QFPDD at clinically relevant doses, and differentially expressed miRNAs (DEMs) in serum were identified via miRNA sequencing. Core targets of the DEMs were predicted using miRanda, TargetScan, and AlphaFold3. Then, according to the metabolic flux catalyzed by the predicted target, serum metabolomic analysis was employed to evaluate DEM regulation by examining changes in corresponding metabolites. Metabolomic profiling was also performed on both serum and QFPDD to identify exogenous metabolites and their origins. Additionally, in vitro antiviral activity of the DEM was assessed using human coronavirus 229E (HCoV-229E).

Results: QFPDD downregulated novel-miR-89. Two key phospholipase C (PLC) mRNAs—encoding phosphatidylcholine (PC)-specific PLC (PC-PLC) and PLC gamma 1 (PLCγ1)—were predicted as direct targets of novel-miR-89. Downregulation of novel-miR-89 enhanced PLC/protein kinase C (PKC) pathway activity, supported by decreased PC levels and increased phosphorylcholine and 13S-hydroxyoctadecadienoic acid (13S-HODE) levels in the QFPDD group. PC abundance showed a positive linear correlation with novel-miR-89 expression (r ≈ 0.5, P < 0.05), while 13S-HODE exhibited a negative correlation (r = -0.5, P < 0.05). Knockdown of novel-miR-89 suppressed HCoV-229E replication in vitro. Moreover, serum levels of glycyrrhetinic acid (GA) increased in QFPDD-treated rats due to hydrolysis of glycyrrhizic acid from the decoction. GA contributed to anti-inflammatory effects by inhibiting 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)

Conclusion: QFPDD exerts its therapeutic effects through dual synergistic mechanisms: an antiviral axis mediated by the Novel-miR-89/PLC/PKC pathway and an anti-inflammatory pathway initiated by the GA/11β-HSD2 pathway.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC

PROVIDER: MTBLS13283 | MetaboLights | 2025-11-08

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13283_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13283_LC-MS_positive_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13283.txt	Txt

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Project description:Background Also the traditional Chinese medicine (TCM) theory of "Yang transforming into Qi with Yin constituting Form" was recognized as a potential mechanism underlying the tumorigenesis. The decoction based on this theory and the underlying molecular mechanisms remained exploration. Methods A TCM decoction was prepared based on "Yang transforming into Qi with Yin constituting Form". Its anti-tumorigenesis effect was evaluated on mouse models of hepatocellular carcinoma (HCC) (H-rasG12V transgenic mice (Ras-Tg) and Diethylnitrosamine (DEN)-induced HCC mice) by liver/body weight, number and size of tumors, histopathological changes and serum biochemistry. RNA sequencing was utilized to check differentially expressed genes (DEGs) and gene ontology (GO) and KEGG were used for bioinformatics analysis. The concerned biological processes were further confirmed by RT-qPCR and metabolite detection kits. Results The TCM decoction significantly suppressed both Ras oncogene- and DEN-induced hepatic tumorigenesis evidenced by reduced serum ALT and AST levels, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes. RNA sequencing showed 659 up-regulated genes and 222 down-regulated genes in comparison of liver tissues between TCM-treated and untreated Rag-Tg (n=5). GO entries and KEGG analysis revealed multiple biological processes and pathways involving the hepatic tumorigenesis suppressing effective of the TCM. Further molecular examination confirmed that activation of retinal metabolism, reduction of ROS and electrophilic levels by inhibiting the H2O2 production and promoting GSH production, and inhibition of expression of inflammation factors play pivotal roles in the anti-tumorigenesis effects of TCM. Conclusion A TCM decoction based on "Yang transforming into Qi with Yin constituting Form" showed effective anti-hepatic tumorigenesis functions and its regulation functions on retinal, ROS and inflammation processes play important roles. The present study provides valuable clue for clinical therapy on tumorigenesis.

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Differently Regulated Metabolites by Qingfei Paidu Decoction

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