Salvianolic acid B inhibits melanoma via dual modulation of glycolysis and NK/T cell immunity.

Optimization of sequential smashing tissue-microwave assisted extraction and resin purification of salvianolic acids from Salviae miltiorrhizae Radix et Rhizoma using a hybrid RSM-ANN-GA model

This is the first study aiming to investigate the yield and kinetics of supercritical CO2 extraction of peppermint (Mentha piperita L.) seeds, as well as to evaluate fatty acid and phenolic composition, antioxidant activity and cytotoxic properties against human lung adenocarcinoma (A549 cells) and normal fetal fibroblast (MRC-5 cells) of the obtained extracts. Applied conditions of pressure and temperature for extraction were in the range of 10-30 MPa and 40-50 °C. A significant increase in the yield was revealed at higher conditions of pressure and temperature. More than 80% of detected fatty acids belong to unsaturated fatty acids, with a predominant content of polyunsaturated fatty acids. With increasing pressure and temperature, the percentage of saturated and polyunsaturated fatty acids increased, whereas the amount of monounsaturated fatty acids decreased. The prenominal compounds in all tested samples were salvianolic acid, followed by rosmarinic acid and eriodictyol. Due to the highest content of individual phenolic compounds, optimal treatment for the phenolic compound extraction was 20 MPa and 40 °C. The sample extracted at the lowest pressure and the lowest temperature exhibited the most potent cytotoxicity against A549 cells. Peppermint seeds represent a high-value material that should be more extensively studied and encouraged for application in the food industry sector. © 2025 Society of Chemical Industry.

NIN-like proteins (NLPs) are plant-specific transcription factors with a conserved RWP-RK domain that can bind to nitrate-responsive cis-elements (NREs) in target gene promoters. NLPs play essential roles in nitrogen uptake, transport, metabolism, and are also involved in nitrate signaling, root development, and secondary metabolism. Salvia miltiorrhiza is a medicinal plant valued for its roots and rhizomes. It mainly contains two types of active ingredients: tanshinones and salvianolic acids. Previous studies have shown that nitrogen availability significantly affects the growth of S. miltiorrhiza and the accumulation of its active ingredients, but the regulatory mechanism has not yet been fully elucidated. In this study, 11 SmNLPs were identified in the S. miltiorrhiza genome through bioinformatic analyses, and they were found to be distributed across eight chromosomes. Phylogenetic analysis grouped them into three subfamilies, with members in the same clade sharing similar gene structures and conserved domains. Promoter analysis revealed that SmNLPs harbor cis-acting elements involved in stress responses, hormone signaling, development, and light responses. Tissue-specific expression analysis of two-year-old S. miltiorrhiza plants showed that SmNLPs are broadly expressed in roots, stems, leaves, and flowers, exhibiting distinct tissue-specific patterns. Among them, most SmNLPs, particularly SmNLP3andSmNLP8, were significantly upregulated in nitrogen-deprivation hairy roots. Co-expression analysis based on transcriptome data suggested that SmNLP3, SmNLP8, and SmNLP10 may be involved in the regulation of tanshinone and salvianolic acid biosynthesis. These findings provide new insights into the potential roles of NLPs in nitrogen response and secondary metabolism in S. miltiorrhiza, laying a foundation for future functional studies and metabolic engineering.

Colorectal cancer (CRC) progression is driven by diverse molecular mechanisms, underscoring the urgent need for novel therapeutic strategies, especially for liver metastases. Through an integrated analysis of multiple single-cell RNA sequencing databases, zinc finger protein-like 1 (ZFPL1) is identified as a gene specifically enriched in malignant cells from both primary and metastatic CRC. Multi-omics investigations demonstrate that high ZFPL1 expression correlates with aggressive clinicopathological features and poor survival. Functionally, ZFPL1 promotes tumor proliferation, invasion, and migration both in vivo and in vitro. Mechanistically, ZFPL1 directly binds argininosuccinate synthase 1 (ASS1), shielding its K57 residue from tripartite motif containing 33-mediated ubiquitination to prevent proteasomal degradation. This stabilization activates urea cycle metabolism, driving CRC progression. Crucially, ZFPL1 deficiency remodels the tumor microenvironment by reducing immunosuppressive populations-M2 macrophages, and promoting pro-inflammatory M1 polarization. Virtual screening identifies Salvianolic acid B (Sal B) as a ZFPL1 inhibitor, which disrupts ZFPL1-ASS1 binding, triggering ASS1 ubiquitination and degradation. In vivo, Sal B synergized with anti-PD-1 therapy, significantly reducing tumor burden versus monotherapy. These findings establish ZFPL1 as a key regulator of CRC progression through ASS1-dependent urea cycle activation and immunomodulation, nominating the ZFPL1-ASS1 axis as a therapeutic target, with Sal B demonstrating combinatorial potential with immunotherapy.

Salvianolic acid A (SAA), a major water-soluble bioactive compound extracted from Salvia miltiorrhiza, has been extensively studied for its diverse pharmacological properties in cerebrovascular diseases. However, its immunomodulatory effects on lymphocytes in stroke remain incompletely understood. This study systematically investigated the therapeutic efficacy and underlying mechanisms of SAA in a murine model of transient middle cerebral artery occlusion (tMCAO). Early administration of SAA (20mg/kg) to ischemic stroke (IS) mice demonstrated neuroprotective effects, characterized by reduced infarct volume and improved behavioral outcomes, alongside creating a Treg-favorable environment in the spleen. In T cells differentiation assays and a luciferase reporter gene system, SAA was further identified as the primary active component in Salvia miltiorrhiza extract responsible for promoting in vitro Treg differentiation. Flow cytometry analysis revealed that SAA treatment significantly enhanced the accumulation of Treg cells in the brain after tMCAO, potentiated the immunosuppressive profile of the cerebral microenvironment, alleviated inflammatory responses, and avoided inducing systemic immunosuppression, ultimately leading to substantial neurological improvement. Treg depletion abolished SAA-induced neuroprotection. Mechanistically, SAA appeared to regulate Treg differentiation through the RUNX1/CBFβ/FOXP3 axis independent of TGF-β signaling. In summary, these findings suggest that SAA improved stroke outcomes via upregulation of cerebral Treg cells abundance, a process linked to the RUNX1/CBFβ/FOXP3 pathway. Collectively, this study offers new perspectives on the therapeutic potential of SAA in ischemic stroke management.

Gastrointestinal (GI) cancers remain a significant global health burden with high mortality rates. Chinese herbal medicine (CHM) has emerged as a complementary therapy, yet limited real-world evidence regarding its use and effectiveness in GI cancers. This scoping review evaluated findings on CHM usage patterns and survival outcomes in GI cancer patients from studies using the Taiwan National Health Insurance Research Database, a uniquely data source covering 99.99% of the Taiwanese population. Five databases were searched for studies from January 1, 1997, to November 30, 2024. Information on exposures and outcomes were extracted, alongside study designs, patient characteristics, methodologies, and results. We identified seven studies focusing on liver (n = 3), gastric (n = 2), pancreatic (n = 1) and colon (n = 1) cancers. Of the 6 studies that evaluated usage patterns, Bai-Hua-She-She-Cao (Oldenlandia Diffusae Herba) and Dan-Shen (Salviae Miltiorrhizae Radix et Rhizoma) were the most frequently used herbs among Taiwanese GI cancer patients. Of the 6 studies that investigated survival, complementary CHM use was associated with lower mortality (adjusted HRs = 0.41-0.68) compared to conventional treatment only. Subgroup analyses showed longer durations of CHM use were associated with greater survival benefits. However, potential for confounding and bias tempers any conclusions. This review underscores the potential role of CHM as a complementary treatment for improving survival in GI cancers in real-world settings. These findings will require future rigorously-designed multinational observational studies and trials to further identify the role of specific herbal treatment in contemporary oncological care to improve outcomes for people with GI cancer.

Salvianolic acid A targets glutamic-oxaloacetic transaminase 2 to ameliorate doxorubicin-induced myocardial oxidative injury by activating malate-aspartate NADH shuttle.

ABSTRACT A cost‐effective and straightforward vortex‐assisted matrix solid phase dispersion (VA‐MSPD) method was developed for extracting phenolic compounds from Salvia miltiorrhiza . UIO‐66‐NH 2 and 7 mL of 79% methanol aqueous solution containing 478 mM ionic liquid ([BMIM][BF4]) were selected as the dispersing sorbent and eluent, respectively. The optimal conditions were determined as follows: sample‐to‐dispersant mass ratio of 3.5:1, grinding time of 4 min, a vortex time of 2 min. Based on these results, response surface methodology (RSM) was further employed to investigate the effects of three key factors (sample‐to‐dispersant mass ratio, ionic liquid concentration, and methanol volume fraction) and their interactions on phenolic acids extraction efficiency. In addition, the combination of matrix solid‐phase dispersion and high‐performance liquid chromatography (HPLC) permitted the determination of four major natural polyphenolic compounds, including danshensu, rosmarinic acid, salvianolic acid B, and salvianolic acid A. The method demonstrated good linearity, showing limit of detection (LOD) of 0.13–0.28 µg·mL −1 and limit of quantitation (LOQ) of 0.42–0.92 µg·mL −1 . The developed vortex‐assisted matrix solid phase dispersion (VA‐MSPD) method showed higher extraction efficiency, greater convenience, and reduced time, making it an excellent choice for analyzing active components in traditional Chinese medicinal herbs.

Dynamic remodeling of pectin and hemicellulose for contrastive cadmium accumulations with root cell walls in distinct Salvia miltiorrhiza ecotypes.

Optimization of extraction methods, component identification of bound polyphenols from sea-buckthorn pomace, and its ameliorative effects on oxidative stress in sleep-deprived mice.

Integrated omics reveals a SmGBF1-SmGDH3 model that facilitates the accumulation of salvianolic acid B under flooding.

ROS-Responsive Hydrogel Loaded with Sodium Tanshinone IIA Sulfonate and Salvianolic Acid B: Preparation, Characterization, Its Biological Effects on Scar Fibroblasts and Anti-Scar Efficacy Study

Metal-polyphenol nanocomposite hybrid hydrogel: A multifunctional platform for treating diabetic foot ulcers through metabolic microenvironment reprogramming.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.

Protection against stroke-induced blood-brain barrier disruption by Guanxinning injection and its active-component combination via TLR4/NF-κB/MMP9-mediated neuroinflammation.

To explore the anti-photoaging properties of salvianolic acid B (Sal B). The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking. Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol. Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.

The distribution of Danqi tongmai tablet in rats at different timeframe by UHPLC-LTQ-orbitrap mass spectrometry and nanospray desorption electrospray ionization mass spectrometry imaging.

BackgroundSalvianolic acid B (Sal B), a natural polyphenol with potential therapeutic applications, has been reported to induce reactive oxygen species (ROS) generation. However, its underlying mechanism has not yet been fully elucidated. In this study, we investigated copper-mediated oxidative DNA damage induced by Sal B.ResultsSal B significantly increased the level of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in HL-60 cells, but not in H2O2-resistant HP100 cells. The formation of 8-oxodG was inhibited by a Cu(I)-specific chelator. These results suggested that Cu(I) and H2O2 play critical roles in this process. In calf thymus DNA, Sal B induced 8-oxodG formation in the presence of Cu(II), which was markedly enhanced in the presence of NADH. Using 32P-5′-end-labeled DNA fragments, we showed that treatment with Sal B in combination with Cu(II) and NADH caused DNA strand breaks and site-specific base modification, especially at thymine and cytosine residues. These results suggest the involvement of ROS other than •OH and this was further supported by radical scavenger experiments. Furthermore, theoretical calculation data suggest that one of the catechol groups in Sal B is electron-donating. Collectively, these results indicate that Cu(II)-mediated autoxidation of the catechol group in Sal B generates Cu(I) and H2O2, likely leading to a Cu(I)-hydroperoxide complex formation and resultant oxidative DNA damage. NADH enhances ROS production and oxidative DNA damage by reducing oxidized Sal B and promoting its recycling.ConclusionsThe potential pro-oxidant risk of Sal B should be carefully evaluated when used as a therapeutic agent.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41021-025-00344-w.

Peptide hormones play crucial roles as signaling regulators in plant development and environmental adaptation. This study identified the Salvia miltiorrhiza CLE peptide SmCLE25, which is involved in regulating leaf senescence and multiple stress responses. SmCLE25 transcription is upregulated by ABA, JA, high salinity, and drought stresses. Application of synthetic SmCLE25 mature peptide significantly enhanced S. miltiorrhiza resistance to salt and drought tolerance. Overexpression of SmCLE25 in Arabidopsis thaliana delayed senescence and enhanced drought resistance. Seed germination assays demonstrated that elevated SmCLE25 expression enhanced germination efficiency under salt and drought conditions. Mechanistic analysis revealed that SmCLE25 peptide reduces reactive oxygen species (ROS) accumulation under stress by downregulating ROS biosynthesis-related genes RbohC and RbohE. This study provides novel insights into the regulatory mechanisms of peptide signaling in leaf senescence and stress adaptation to salinity and drought.