Current Pharmaceutical Design - Volume 32, Issue 10, 2026

Salvianolic acid B (SAB), as one of the major water-soluble compounds of Salvia miltiorrhiza, has proved to effectively reduce elevated portal pressure in cirrhotic rats. However, the short half-life and in vivo retention time of SAB affect its pharmacodynamics. Therefore, in this study, we prepared albumin nanoparticles loaded with SAB (SAB-ALB-NPs) to improve the in vivo retention time of the drug and enhance bioavailability.

We prepared and characterized SAB-ALB-NPs, including particle size, polydispersity index (PDI), zeta potential, stability, EE, in vitro release, and pharmacokinetics. Subsequently, we investigated the effects and potential mechanisms of SAB-ALB-NPs in CCl4-induced portal hypertension (PHT) mice models, and it was found that angiotensin-II (Ang-II) induced proliferation and contraction in hepatic stellate cells (HSCs). The CCl4 (0.3:1 in corn oil, 1mL/kg) was injected repeatedly, leading to the PHT mice model. The effect of SAB-ALB-NPs on PHT mice was evaluated by hematoxylin-eosin, Sirius red staining, immunohistochemistry, and Western blot.

We successfully prepared SAB-loaded albumin nanoparticles with smaller-sized particles, lower PDI and zeta potential with stable properties, and higher EE. Importantly, the SAB-ALB-NPs notably prolonged the in vitro release of SAB. SAB-ALB-NPs significantly reduced portal pressure, inhibited inflammation (decrease the concentration of TNF-α and IL-6) and hepatotoxicity of the liver (down-regulated the level of ALT and AST) against fibrous tissue hyperplasia, and reduced collagen deposition in the liver. Afterward, we used Ang-II to facilitate the proliferation of HSCs and induce HSC cell contraction. Cotreatment of SAB-ALB-NPs markedly inhibited Ang II-induced effects on cell proliferation and contraction and improved apoptosis. Importantly, SAB-ALB-NPs were preliminarily found to inhibit the expression of RhoA and ROCK II in Ang-II-treated HSC and CCl4-induced PHT mice, suggesting that SAB-ALB-NPs may participate in the regulation of RhoA/ROCK II pathway.

SAB-ALB-NPs improved portal hypertension by suppressing inflammation and inhibiting HSCs activation and proliferation to attenuate liver fibrosis. This therapeutic function of SAB-ALB-NPs may be owing to SAB-ALB-NPs regulating the RhoA/ROCK2 pathway, which may be one of its molecular mechanisms for reducing portal hypertension.

Oral Submucosal Fibrosis (OSF) is a chronic progressive oral mucosal disease with a tendency to progress to cancer. Astragalus membranaceus (AST) is a traditional Chinese medicine used to invigorate Qi and strengthen the body, with anti-fibrosis properties. However, the effect and mechanism of AST on OSF remain unclear.

This study aims to explore the mechanism of Astragalus membranaceus in OSF using network pharmacology and to validate its effects on oral mucosal fibroblasts through in vitro experiments.

Network pharmacology was employed to construct an “AST - ingredient - target - OSF” network and perform Protein-Protein Interaction (PPI) analysis. Molecular docking was used to confirm core interactions between key targets and ingredients, and all results met the criterion of a binding energy of <- -1.2 kcal/mol. In vitro experiments were conducted to assess the cytotoxicity of arecoline (ARE) and Astragalus membranaceus injection (ASI) on Oral Mucosal Fibroblasts (OMF).

Analysis revealed 68 common targets between AST and OSF, and a corresponding PPI network was constructed. KEGG and GO enrichment analyses identified 138 pathways and 178 biological processes associated with these targets. Molecular docking confirmed core interactions between five key targets (EGFR, VEGFA, MAPK3, HRAS, JUN) and other ingredients. In vitro experiments showed that ARE at concentrations of 20-40 µg/ml significantly upregulated ACTA2, EGFR, and VEGFA mRNA expression. ASI treatment at varying concentrations significantly inhibited these increases, with 100 mg/ml ASI downregulating EGFR and VEGFA mRNA, and 300-400 mg/ml ASI reducing ACTA2 expression.

Astragalus membranaceus injection engages multiple targets and pathways to counteract OSF, aligning with previous antifibrotic evidence and underscoring the need for further in vivo and clinical validation.

Astragalus membranaceus injection may suppress ARE-induced fibrosis by targeting EGFR and VEGFA, supporting its potential therapeutic role in the treatment of OSF.

Statins are widely prescribed for cardiovascular disease prevention, but their potential to increase diabetes risk has prompted regulatory warnings. Different statin drugs have varying physicochemical properties, yet comprehensive comparative assessments of their individual diabetes-related safety profiles remain limited in post-marketing surveillance data. Therefore, this study aimed to evaluate and compare the risk of diabetes-related adverse events among different statin drugs using pharmacovigilance data.

We analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2022. Diabetes-related adverse events were identified using relevant MedDRA Preferred Terms. Four pharmacovigilance algorithms—Reporting Odds Ratio (ROR), Medicines and Healthcare products Regulatory Agency (MHRA) standard method, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinkage—were employed to detect signals. Positive signals were defined when all four methods showed significance. Outcome severity and time-to-event were also analyzed.

Among 13,438,409 ADE reports, 63,583 identified statins as primary suspect drugs, with 11,562 reporting diabetes-related events. Positive signals were detected for atorvastatin, rosuvastatin, simvastatin, pravastatin, and pitavastatin. Signal strength ranking showed atorvastatin had the strongest association (ROR 36.70; 95% CI 35.92-37.51), followed by rosuvastatin (ROR 9.63; 95% CI 9.10-10.19), pitavastatin (ROR 5.46; 95% CI 4.03-7.41), simvastatin (ROR 2.96; 95% CI 2.54-3.45), and pravastatin (ROR 2.82; 95% CI 2.14-3.71). In patients under 45, only atorvastatin showed a positive signal. Atorvastatin was associated with a higher risk of serious adverse events (PRR=1.37; 95% CI: 1.09-1.71) with a median time to event of 1,012 days.

Our findings revealed differences in diabetes-related risk profiles among statins, with atorvastatin demonstrating the strongest signals across different age groups. The observed risk hierarchy may be attributed to differences in lipophilicity, potency, and metabolic effects. The age-dependent patterns and extended time-to-event for diabetic events underscore the importance of long-term monitoring, complementing clinical trial data with post-marketing surveillance evidence for improved statin selection.

Different statins demonstrate varying associations with diabetes-related adverse events, with atorvastatin showing the strongest signal across age groups. These findings may inform clinical decision-making when prescribing statins, particularly for patients with pre-existing diabetes risk factors.

Diabetic kidney disease (DKD) is a devastating complication of diabetes for which there are few potent treatments.Triptolide (TP), an active compound from Tripterygium wilfordii, has shown potential in early studies, but its therapeutic mechanisms in DKD are not fully understood. This study aims to systematically evaluate TP’s efficacy and mechanisms using meta-analysis, network pharmacology, molecular docking, and Mendelian randomization (MR).

A comprehensive search across Chinese and English databases identified animal randomized controlled trials (RCTs) assessing the effects of TP on DKD. A total of 27 studies were incorporated, and a meta-analysis was conducted via Review Manager. TP's drug and disease targets were identified through network pharmacology and molecular docking, while bioinformatics methods were employed to explore the mechanisms. MR analysis was performed to assess potential causal relationships between TP and DKD-related targets.

Meta-analysis showed that TP significantly reduced urinary protein, blood lipids, and glucose levels, while improving renal function, renal weight, and renal index (all p < 0.05). Seven core targets—IFNG, CXCL8, TNF, TGFB1, IL2, IL4, and RELA—were identified via network pharmacology, involving key pathways such as lipid-atherosclerosis, AGE-RAGE, and IL-17 signaling. Molecular docking demonstrated strong binding affinities between TP and these targets, with binding energies below -7.00 kJ/mol. Although MR analysis did not establish direct causal relationships between these core genes and DKD, a significant negative correlation between TNF, IL4, and GFR was observed, suggesting their involvement in DKD progression.

TP may exert therapeutic effects on DKD through coordinated regulation of immune and inflammatory pathways. The integration of multi-omics approaches supports its multi-target pharmacological mechanisms. Although MR analysis did not confirm direct causal relationships, the identified gene associations further reinforce the potential biological relevance of TP. However, this study was primarily based on public datasets and lacks experimental validation in vivo and in vitro.

TP exerts therapeutic effects on DKD through multi-target and multi-pathway mechanisms, primarily involving immunomodulation, anti-inflammation, anti-oxidation, and anti-fibrosis processes.