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<p>This study integrated network pharmacology and experimental validation to elucidate the mechanism of Longdan Xiegan Pills (LDXG) in treating chronic stress-induced hypertension. Active components of LDXG were retrieved from the TCMSP database and screened based on oral bioavailability (OB) and drug-likeness (DL). Potential targets were predicted using SwissTargetPrediction. Disease targets related to hypertension were collected from OMIM and GeneCards. A compound-target network was constructed using Cytoscape, and protein–protein interaction (PPI) analysis was performed via the STRING database. Functional enrichment analysis (GO and KEGG) was conducted using DAVID. Molecular docking was performed with LeDock. In vivo, systolic and diastolic blood pressures were measured non-invasively, myocardial histopathology was evaluated by HE staining, the content of target protein in pvn and adrenal gland was measured by western blot, and serum inflammatory markers were quantified via ELISA. A total of 178 active components of LDXG were screened, Gentiana scabra Bunge (Gentian), Gardenia jasminoides Ellis (Gardeniae fructus), Scutellaria baicalensis Georgi (Huangcen), Bupleurum chinense DC (Bupleurum), and Glycyrrhiza uralensis Fisch (Licorice) were identified as the core components.The core targets included SRC, MAPK3, MAPK1, PIK3R1, RELA and STAT3. GO functional enrichment and KEGG pathway enrichment analyses indicated that LDXG primarily modulated protein kinase activity, ATP binding, protein serine/threonine kinase activity and protein kinase binding.These processes involved the PI3K-Akt, HIF-1, VEGF, ErbB and FoXO. Animal experiments demonstrated LDXG can significantly lowered blood pressure level in chronic stress-induced hypertension rats,reduced the contents of src and STAT3 in the PVN and MAPK1 in the adrenal gland and reduced serum levels of angiotensin II (Ang II), cortisol and adrenocorticotropic hormone(ACTH). LDXG can attenuate chronic stress hypertension by regulating JAK/STAT, Src/MAPK and other signaling pathways and reducing the expression of Ang II through a variety of active compounds.</p> Graphical Abstract <p></p>

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The mechanism of Longdan Xiegan pills in chronic stress-induced hypertension:a study based on network pharmacology and experimentalvalidation

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Huizhuo Jia,
  • Mingyao Lv,
  • Ying Yang,
  • Zhe Wang,
  • Yanzhao Zhang,
  • Jinxu Zhou,
  • Longfei Xia,
  • Jing Zhang,
  • Haifu Wan,
  • Na Li

摘要

This study integrated network pharmacology and experimental validation to elucidate the mechanism of Longdan Xiegan Pills (LDXG) in treating chronic stress-induced hypertension. Active components of LDXG were retrieved from the TCMSP database and screened based on oral bioavailability (OB) and drug-likeness (DL). Potential targets were predicted using SwissTargetPrediction. Disease targets related to hypertension were collected from OMIM and GeneCards. A compound-target network was constructed using Cytoscape, and protein–protein interaction (PPI) analysis was performed via the STRING database. Functional enrichment analysis (GO and KEGG) was conducted using DAVID. Molecular docking was performed with LeDock. In vivo, systolic and diastolic blood pressures were measured non-invasively, myocardial histopathology was evaluated by HE staining, the content of target protein in pvn and adrenal gland was measured by western blot, and serum inflammatory markers were quantified via ELISA. A total of 178 active components of LDXG were screened, Gentiana scabra Bunge (Gentian), Gardenia jasminoides Ellis (Gardeniae fructus), Scutellaria baicalensis Georgi (Huangcen), Bupleurum chinense DC (Bupleurum), and Glycyrrhiza uralensis Fisch (Licorice) were identified as the core components.The core targets included SRC, MAPK3, MAPK1, PIK3R1, RELA and STAT3. GO functional enrichment and KEGG pathway enrichment analyses indicated that LDXG primarily modulated protein kinase activity, ATP binding, protein serine/threonine kinase activity and protein kinase binding.These processes involved the PI3K-Akt, HIF-1, VEGF, ErbB and FoXO. Animal experiments demonstrated LDXG can significantly lowered blood pressure level in chronic stress-induced hypertension rats,reduced the contents of src and STAT3 in the PVN and MAPK1 in the adrenal gland and reduced serum levels of angiotensin II (Ang II), cortisol and adrenocorticotropic hormone(ACTH). LDXG can attenuate chronic stress hypertension by regulating JAK/STAT, Src/MAPK and other signaling pathways and reducing the expression of Ang II through a variety of active compounds.

Graphical Abstract