To investigate the therapeutic efficacy of Cynomorium songaricum Rupr. (C. songaricum, Suo Yang) polysaccharide (CSP) against pulmonary hypertension (PH) and explore whether its effects are associated with modulation of the phosphodiesterase type 5-cyclic guanosine monophosphate-protein kinase G (PDE5-cGMP-PKG) signaling pathway using both in vivo rat models and in vitro cultures of rat pulmonary arterial smooth muscle cells (RPASMCs).

A rat model of PH was established via monocrotaline (MCT) administration, followed by daily oral gavage of CSP at low, medium, and high doses for 28 consecutive days. Hemodynamic parameters, including right ventricular systolic pressure (RVSP), were measured using right heart catheterization (RHC). Meanwhile, right ventricular hypertrophy indices (RVHI) and electrocardiographic parameters underwent systematic evaluation. For the in vitro assays, RPASMCs were exposed to Cobalt (Ⅱ) chloride (CoCl₂) to establish a hypoxia-like injury model and then treated with CSP to evaluate its effects on cell proliferation, migratory capacity, and intracellular cGMP content.

In vivo, CSP treatment dose-dependently mitigated MCT-induced hemodynamic dysfunction (e.g., RVSP and mPAP, P < .001), alleviated pathological pulmonary vascular remodeling (WA% and WT%, P < .001), mitigated right ventricular hypertrophy secondary to pressure overload (RVHI, P = .015), and reversed abnormal electrocardiographic manifestations in PH rats (e.g., QTc, P = .007; QRS, P = .010). In vitro, CSP markedly inhibited the CoCl₂-triggered excessive proliferation (CCK-8, P = .013; EdU, P = .003) and migration (Transwell and wound-healing assays, P < .001) of RPASMCs and simultaneously restored the reduction in intracellular cGMP levels induced by hypoxic exposure (P = .008).

CSP exerts remarkable therapeutic effects against PH, mainly by inhibiting phosphodiesterase 5 and restoring the cGMP-PKG signaling cascade. These findings provide preclinical support for further investigation of CSP as a potential therapeutic candidate for PH.

To explore the mechanism of action of Zangjiangzhi capsule (ZJZC) in treating hyperlipidemia (HLP).

The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS/MS). Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment. The SwissTargetPrediction database was used to predict compound targets, and GeneCards, DisGeNet, OMIM, and DRUGBANK databases were used to identify HLP-related targets. Protein–protein interaction diagrams were constructed using the STRING database. The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The “herb-ingredient-target” network was visualized using Cytoscape. Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay.

Ninety compounds were identified in ZJZC, including 34 flavonoids, 12 phenols, 10 terpenoids, 10 alkaloids, 8 organic acids, 8 anthraquinones, and 9 other compounds. In total, 904 targets were identified for these compounds. Among them, 158 targets intersected with the HLP target network. Network pharmacology analysis showed that MAPK1, PPAR-α, RXRA, HSP90AA1, PIK3R1, AKT1, PIK3CA, IL6, TNF, and ESR1 are the key targets of action. KEGG enrichment analysis identified 164 pathways. Among these, the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis pathways, regulation of lipids in adipocytes, and insulin resistance are related to HLP. Molecular docking showed good affinity between the key targets and ingredients. Further, ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-α protein, which have been shown to be strongly associated with HLP.

This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP, providing evidence at the molecular level for its clinical application in the treatment of HLP.

To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine (TCM) based on the regulation of gene expression.

Genome-wide gene expression profiles of Michigan Cancer Foundation-7 (MCF-7) cells treated with or without 4 cholic acid derivatives were detected by gene chip technology. Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map (CMap) database. The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking. The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database, and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells.

Compared with the reference genome in the CMap database, the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic, anticancer, anti-inflammatory, and anti-infective drugs. Among them, 4 derivatives were associated with antianxiety drugs, and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gamma-aminobutyric acid (GABA) receptors. Moreover, the cytoskeletal pathway is one of the pathways enriched in the derivatives. Of them, ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.

The gene expression detection method, combined with CMap and pathway enrichment analysis, could be used to study the mechanism of the active ingredients of TCM. In addition, our research showed that cholic acid derivatives have a potential affinity for membrane receptors, where they can exert anxiolytic activity by modulating opioid receptor, GABA receptor, and dopamine receptor. Moreover, ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation, probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.