Current Pharmaceutical Design - Volume 31, Issue 40, 2025

Radiation therapy is a crucial method used to treat various tumors, but it can lead to radiation pneumonitis. Shashen Maidong Decoction (SMD) is clinically used to treat radiation pneumonitis, but the exact mechanism remains unclear.

Herbal components and targets of SMD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Encyclopedia of Traditional Chinese Medicine (ETCM), and Swiss Target Prediction platforms. Moreover, disease-related targets were retrieved from the GeneCards database. A Protein-protein Interaction (PPI) network was constructed using the STRING database and analyzed using the Cytoscape software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID database. Subsequently, the disease-active component-target network and drug-pathway-target network were constructed using Cytoscape. The molecular docking results were validated and visualized using Auto Dock and PyMOL software.

In this study, 115 conserved active ingredients, 316 drug targets, and 355 radiation pneumonitis targets were identified. Among these, 75 targets were identified as intersecting targets. GO enrichment analysis revealed 494 biological processes, 36 cell components, and 59 molecular functions. KEGG analysis uncovered 118 signaling pathways, including the IL17 signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, etc. The molecular docking results showed the core active ingredients of SMD, including quercetin, kaempferol, beta-carotene, and naringenin, to have strong binding ability with the core targets.

This study preliminarily confirmed that SMD may act on the TNF, IL17, and HIF-1 signaling pathways to exert its therapeutic effects on radiation pneumonitis by regulating the expression of inflammatory factors.

Doxorubicin (DOX) is a widely used anthracycline antibiotic for the treatment of breast cancer, liver cancer, lymphoma, and other malignant tumors. However, its clinical application is limited by the side effects and drug resistance. Astragalus injection has been combined with DOX in the treatment of cancer, which improves the curative effect and reduces drug resistance. This study investigated the interaction between DOX and Astragalus injection and elucidated the potential mechanism.

The pharmacokinetics of DOX injection (7 mg/kg, intraperitoneal injection) with or without Astragalus injection (4.25 mL/kg/day for 14 days, intraperitoneal injection) were investigated in plasma from male Sprague-Dawley rats (n = 6) by UPLC-MS/MS. The group without the Astragalus injection was set as the control group. Additionally, the effects of Astragalus injection on CYP450 enzyme activities were assessed using a rat liver microsome incubation system with cocktail probe drugs.

Astragalus injection significantly increased the Cmax (2090.01 ± 99.60 vs. 5262.77 ± 111.15 ng/mL) and AUC0-t (1190.23 ± 104.43 vs. 3777.27 ± 130.55 μg/L × h) and prolonged the t1/2α (0.09 ± 0.02 vs. 0.14 ± 0.04 h) of DOX. Astragalus injection significantly inhibited the activity of CYP1A2, CYP2C9, CYP2E1, and CYP3A4, and enhanced the activity of CYP2D1 with a metabolic elimination rate of 30.11 ± 2.67% vs. 19.66 ± 3.41%, 35.95 ± 2.57% vs. 23.26 ± 3.57%, 13.43 ± 2.56% vs. 9.06 ± 2.51%, 47.90 ± 6.30% vs. 25.87 ± 2.55%, 17.62 ± 1.49% vs. 24.12 ± 2.91%, respectively (p < 0.05).

The co-administration of DOX and Astragalus injection alters the systemic exposure of DOX by affecting the metabolism of DOX and the activity of CYP450 enzymes. These findings highlight the importance of drug-drug interactions when combining Astragalus injection with DOX and provide a basis for optimizing combination therapies to address DOX resistance and toxicity.

This study aims to valorise cheese whey waste by converting it into bioactive peptides that have several health benefits, potentially leading to the development of nutraceuticals and functional foods and also used in the pharmaceutical industry.

The study evaluates the antidiabetic, antioxidative, and anti-inflammatory properties of fermented cheese whey with Limosilactobacillus fermentum (M4), along with the production of antioxidative and antidiabetic peptides. SDS-PAGE and 2D-PAGE were also performed to identify proteins by molecular weight and isoelectric point, while RP-HPLC distinguished peptide fractions. Peptide sequences from 2D gel spots were identified using RPLC/MS, and RP-HPLC analyzed 3 kDa and 10 kDa permeates. Peakview software characterized the LC/MS results, and FTIR analysis measured structural changes in bioactive peptides.

The antioxidative and antidiabetic properties in cheese whey fermented with M4 showed a progressive growth over extended incubation periods, higher effects were observed after fermentation for 48 hours. Inhibitory activities in α-glucosidase, α-amylase & lipase were found to be 65.39%, 66.09%, and 56.74% respectively. ABTS assay was performed to measure antioxidant activity (63.39%) and the highest proteolytic activity (7.62 mg/ml) was measured at 2.5% inoculation rate for 48 hours. In SDS-PAGE, protein bands between 10 & 30 kDa were observed, whereas peptide spots within the range of 10 to 70 kDa were also visualized on the 2D-PAGE. RP-HPLC was used to distinguish different fractions of a peptide. Peptide sequences from 2D gel spots were identified using RP-HPLC & RPLC/MS. Peakview software was utilized to characterize the LC/MS results. Sequences of peptides generated from α-lactalbumin and β-lactoglobulin were searched in the BIOPEP database to validate the antidiabetic and antioxidative activities of fermented cheese whey peptides. LPS-fermented cheese whey at a concentration of 0.50 mg/mL significantly suppressed the production of pro-inflammatory cytokines as well as the mediators that govern them including IL-6, IL-1β, NO, and TNF-α in RAW 264.7 cells. FTIR was used in the analysis of protein secondary structure and conformational changes.

This study aims to produce antidiabetic and antioxidative peptides from dairy waste and cheese whey.