Salvianolic Acid B Research Articles

Targeting histidinol-phosphate aminotransferase in Acinetobacter baumannii with salvianolic acid B: A structure-based approach to novel antibacterial strategies

Undoubtedly, Acinetobacter baumannii is a major ESKAPE pathogen that poses a significant threat to public health, causing severe nosocomial infections with high mortality rates in healthcare settings. Due to the rapid development of antibiotic resistance, only a limited number of antibiotics remain effective against infections caused by multidrug-resistant (MDR) Acinetobacter baumannii. The discovery of new class of antibiotic molecules still lags behind the rate of growing worldwide burden of antimicrobial resistance (AMR). To expedite the discovery of new therapeutic molecules, we have focused on HisC from A. baumannii (AbHisC), a crucial enzyme involved in the seventh step of histidine biosynthesis. This pathway is absent in humans. We have employed the advanced computational techniques to target this promising drug target. AbHisC was cloned, overexpressed, and purified. Three distinct sets of libraries containing ∼60,000 natural compounds from ZINC database were screened against AbHisC using Schrödinger's glide module software. Based on the docking score and glide energy, top 25 hits were further subjected to induced fit (IF) docking. Top four out of the twenty five compounds from IF docking were subjected to 100ns molecular dynamics simulations, and it was observed that salvianolic acid B (SA-B) (a naturally occurring compound) complex with AbHisC, was found to be extremely stable. The glide energy and docking score of SA-B were −88.59 kcal/mol and −10.4 kcal/mol. SA-B was also found to quench the intrinsic fluorescence of tyrosine indicating its binding to the target. The dissociation constant calculated using Surface Plasmon Resonance was found to be 3.4x10−9 M. Based on these results we can conclude that SA-B can serve as the potential inhibitor of AbHisC that can further form the basis of structure based drug design against this deadly pathogen.

Unveiling the impact of self-assembly on ultrafiltration: Insights from salvianolic acid B

This study explored the influence of self-assembly on the ultrafiltration (UF) rejection of salvianolic acid B (SaB), a model polyphenolic compound. Employing a combined approach of experimental analysis and molecular dynamics simulations (MDS), we demonstrated pH-dependent self-assembly of SaB at both macroscopic and microscopic levels. At lower pH, larger self-assemblies formed, exhibiting enhanced adsorption onto the membrane surface due to electrostatic attraction. This pH-dependent behavior significantly impacted rejection rates through size exclusion and adsorption mechanisms, leading to a decrease in SaB rejection from 100 % to 31 % as the solution pH increased from 2.4 to 5.6. These findings transcend the specific case of SaB, offering valuable insights into the broader role of self-assembly in UF processes. This knowledge holds potential applications in optimizing separation processes across diverse fields such as food, pharmaceuticals, and environmental science.

Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165

BackgroundAberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored.ObjectivesWe aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation.MethodsWe constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge.ResultsHDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10fl/fl-LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI.ConclusionThese results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.

A mussel-inspired, antibacterial, antioxidant, injectable composite hydrogel for the sustain delivery of salvianolic acid B for the treatment of frozen shoulder

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Phospholipids of inhaled liposomes determine the in vivo fate and therapeutic effects of salvianolic acid B on idiopathic pulmonary fibrosis

Since phospholipids have an important effect on the size, surface potential and hardness of liposomes that decide their in vivo fate after inhalation, this research has systematically evaluated the effect of phospholipids on pulmonary drug delivery by liposomes. In this study, liposomes composed of neutral saturated/unsaturated phospholipids, anionic and cationic phospholipids were constructed to investigate how surface potential and the degree of saturation of fatty acid chains determined their mucus and epithelium permeability both in vitro and in vivo. Our results clearly indicated that liposomes composed of saturated neutral and anionic phospholipids possessed high stability and permeability, compared to that of liposomes composed of unsaturated phospholipids and cationic phospholipids. Furthermore, both in vivo imaging of fluorescence-labeled liposomes and biodistribution of salvianolic acid B (SAB) that encapsulated in liposomes were performed to estimate the effect of phospholipids on the lung exposure and retention of inhaled liposomes. Finally, inhaled SAB-loaded liposomes exhibited enhanced therapeutic effects in a bleomycin-induced idiopathic pulmonary fibrosis mice model via inhibition of inflammation and regulation on coagulation-fibrinolytic system. Such findings will be beneficial to the development of inhalable lipid-based nanodrug delivery systems for the treatment of respiratory diseases where inhalation is the preferred route of administration.

Kidney-targeted antioxidant salvianolic acid B nanoparticles restoring lysosome homeostasis for acute kidney injury therapy

Acute kidney injury (AKI) is highly correlated with oxidative stress, and the application of antioxidants is one of the promising treatments. Salvianolic acid B (SAB) is a natural polyphenol with powerful antioxidant effects. Due to its inherent characteristic of inferior bioavailability, its clinical application is impeded. In this study, small SAB-incorporated nanoparticles (SFA) were synthesized via the self-assembly of SAB, ferric ions, and bovine serum albumin (BSA). Apart from antioxidant activity, the SFA nanoparticles were found to efficiently restore lysosome dysfunction induced by reactive oxygen species (ROS) in human kidney proximal tubular epithelial HK-2 cells. The small size and BSA incorporation make the SFA nanoparticles to be promising AKI-targeting nanoparticles. They are rapidly accumulated and long-term retained in injured kidneys of glycerol-induced AKI mice, especially in the proximal tubules which are the key lesion location during AKI. In vivo studies indicate that SFA nanoparticles show a superior protective effect compared with the free drug by suppressing oxidative stress and maintaining lysosome homeostasis indicated by enhanced heme oxygenase-1 (HO-1) expression and restored cathepsin B (CTSB) activity, respectively. In summary, this study develops a delivery system for the antioxidant SAB enhancing local delivery and offering an additional lysosome restoring mechanism for AKI therapy.

Changes in secondary metabolites contents and stress responses in Salvia miltiorrhiza via ScWRKY35 overexpression: Insights from a wild relative Salvia castanea

Salvia castanea Diels, a close wild relative to the medicinal plant, Salvia miltiorrhiza Bunge, primarily grows in high-altitude regions. While the two species share similar active compounds, their content varies significantly. WRKY transcription factors are key proteins, which regulate plant growth, stress response, and secondary metabolism. We identified 46 ScWRKY genes in S. castanea and found that ScWRKY35 was a highly expressed gene associated with secondary metabolites accumulation. This study aimed to explore the role of ScWRKY35 gene in regulating the accumulation of secondary metabolites and its response to UV and cadmium (Cd) exposure in S. miltiorrhiza. It was found that transgenic S. miltiorrhiza hairy roots overexpressing ScWRKY35 displayed upregulated expression of genes related to phenolic acid synthesis, resulting in increased salvianolic acid B (SAB) and rosmarinic acid (RA) contents. Conversely, tanshinone pathway gene expression decreased, leading to lower tanshinone levels. Further, overexpression of ScWRKY35 upregulated Cd transport protein HMA3 in root tissues inducing Cd sequestration. In contrast, the Cd uptake gene NRAMP1 was downregulated, reducing Cd absorption. In response to UV radiation, ScWRKY35 overexpression led to an increase in the accumulation of phenolic acid and tanshinone contents, including upregulation of genes associated with salicylic acid (SA) and jasmonic acid (JA) synthesis. Altogether, these findings highlight the role of ScWRKY35 in enhancing secondary metabolites accumulation, as well as in Cd and UV stress modulation in S. miltiorrhiza, which offers a novel insight into its phytochemistry and provides a new option for the genetic improvement of the plants.

A Comprehensive Strategy Based on High Clinical Translational Nanosystem for Programmable Immunotherapy of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBCs), known as an immunologically cold tumor, is difficult to completely eliminate with existing monotherapies, let alone metastasis and recurrence. It is urgent to design a rational combination of multiple therapies to programmatically reconstitute tumor microenvironment (TME) and reverse the immune "cold" into "hot" inflammatory tumors to improve the therapeutic effect. Hence, in this work, a multifunctional nanosystem (FeSH NPs) that integrates metal-polyphenol coordination complex as a photothermal agent and polyphenol, salvianolic acid B (SAB) as immunomodulator is designed and fabricated for synergistic photothermal-immunotherapy of TNBCs combined with anti-PD-L1 antibody. Guided by photothermal/photoacoustic dual-mode imaging, photothermal therapy (PTT) caused by FeSH NPs induces immunogenic cell death (ICD) under 808nm laser irradiation. Subsequently, the loaded SAB is released with the addition of deferoxamine mesylate (DFO) to remodel TME, specifically TGF-β inhibition and PD-L1 upregulation, and eliminate the primary tumors. The combination of PTT and TME reprogramming by FeSH NPs further synergizes with anti-PD-L1 antibody to eradicate recurrence and inhibit metastasis of TNBCs concurrently. Given the biosafety of FeSH NPs throughout the lifecycle, this work provides a protocol with high clinical translational promise for comprehensive programmed therapeutics of immunologically cold tumors TNBCs.

Injectable Hydrogels Based on Hyaluronic Acid and Gelatin Combined with Salvianolic Acid B and Vascular Endothelial Growth Factor for Treatment of Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) leads to structural damage in the brain, and is one of the major causes of disability and death in the world. Herein, we developed a composite injectable hydrogel (HA/Gel) composed of hyaluronic acid (HA) and gelatin (Gel), loaded with vascular endothelial growth factor (VEGF) and salvianolic acid B (SAB) for treatment of TBI. The HA/Gel hydrogels were formed by the coupling of phenol-rich tyramine-modified HA (HA-TA) and tyramine-modified Gel (Gel-TA) catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). SEM results showed that HA/Gel hydrogel had a porous structure. Rheological test results showed that the hydrogel possessed appropriate rheological properties, and UV spectrophotometry results showed that the hydrogel exhibited excellent SAB release performance. The results of LIVE/DEAD staining, CCK-8 and Phalloidin/DAPI fluorescence staining showed that the HA/Gel hydrogel possessed good cell biocompatibility. Moreover, the hydrogels loaded with SAB and VEGF (HA/Gel/SAB/VEGF) could effectively promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). In addition, the results of H&E staining, CD31 and α-SMA immunofluorescence staining showed that the HA/Gel/SAB/VEGF hydrogel possessed good in vivo biocompatibility and pro-angiogenic ability. Furthermore, immunohistochemical results showed that the injection of HA/Gel/SAB/VEGF hydrogel to the injury site could effectively reduce the volume of defective tissues in traumatic brain injured mice. Our results suggest that the injection of HA/Gel hydrogel loaded with SAB and VEGF might provide a new approach for therapeutic brain tissue repair after traumatic brain injury.

Salvianolic Acid B Reduces Oxidative Stress to Promote Hair-Growth in Mice, Human Hair Follicles and Dermal Papilla Cells.

Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties. To assess the efficacy of SAB in modulating hair growth. In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis. SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38. The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.

Salvianolic Acid B Significantly Suppresses the Migration of Melanoma Cells via Direct Interaction with β-Actin.

Melanoma is the most aggressive and difficult to treat of all skin cancers. Despite advances in the treatment of melanoma, the prognosis for melanoma patients remains poor, and the recurrence rate remains high. There is substantial evidence that Chinese herbals effectively prevent and treat melanoma. The bioactive ingredient Salvianolic acid B (SAB) found in Salvia miltiorrhiza, a well-known Chinese herbal with various biological functions, exhibits inhibitory activity against various cancers. A375 and mouse B16 cell lines were used to evaluate the main targets and mechanisms of SAB in inhibiting melanoma migration. Online bioinformatics analysis, Western blotting, immunofluorescence, molecular fishing, dot blot, and molecular docking assays were carried out to clarify the potential molecular mechanism. We found that SAB prevents the migration and invasion of melanoma cells by inhibiting the epithelial-mesenchymal transition (EMT) process of melanoma cells. As well as interacting directly with the N-terminal domain of β-actin, SAB enhanced its compactness and stability, thereby inhibiting the migration of cells. Taken together, SAB could significantly suppress the migration of melanoma cells via direct binding with β-actin, suggesting that SAB could be a helpful supplement that may enhance chemotherapeutic outcomes and benefit melanoma patients.

3D bioprinting of Salvianolic acid B-sodium alginate-gelatin skin scaffolds promotes diabetic wound repair via antioxidant, anti-inflammatory, and proangiogenic effects

In patients with diabetic wounds, wound healing is impaired due to the presence of persistent oxidative stress, an altered inflammatory response, and impaired angiogenesis and epithelization. Salvianolic acid B (SAB), which is derived from the Chinese medicinal plant Salvia miltiorrhiza, has been found to exhibit antioxidant, anti-inflammatory, and proangiogenic effects. Previous studies have used 3D bioprinting technology incorporating sodium alginate (SA) and gelatin (Gel) as basic biomaterials to successfully produce artificial skin. In the current study, 3D bioprinting technology was used to incorporate SAB into SA-Gel to form a novel SAB-SA-Gel composite porous scaffold. The morphological characteristics, physicochemical characteristics, biocompatibility, and SAB release profile of the SAB-SA-Gel scaffolds were evaluated in vitro. In addition, the antioxidant, anti-inflammatory, and proangiogenic abilities of the SAB-SA-Gel scaffolds were evaluated in cells and in a rat model. Analysis demonstrated that 1.0 wt% (the percentage of SAB in the total weight of the solution containing SA and Gel) SAB-SA-Gel scaffolds had strong antioxidant, anti-inflammatory, and proangiogenic properties both in cells and in the rat model. The 1.0% SAB-SA-Gel scaffold reduced the expression of tumor necrosis factor-α, interleukin-6, and interluekin-1β and increased the expression of transforming growth factor-β. In addition, this scaffold removed excessive reactive oxygen species by increasing the expression of superoxide dismutase, thereby protecting fibroblasts from injury. The scaffold increased the expression of vascular endothelial growth factor and platelet/endothelial cell adhesion molecule-1, accelerated granulation tissue regeneration and collagen deposition, and promoted wound healing. These findings suggest that this innovative scaffold may have promise as a simple and efficient approach to managing diabetic wound repair.

Versatile CYP98A enzymes catalyse meta-hydroxylation reveals diversity of salvianolic acids biosynthesis.

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.

Potential Beneficial Effects of Salvianic Acid A and Salvianolic Acid B in Skin Whitening

Objective Natural product-derived biomaterials are highly desired as possible ingredients in cosmetics, as they are often safe and effective. Salvianic acid A (SAA) and salvianolic acid B (SAB) are the primary water-soluble ingredients of Salvia miltiorrhiza Bunge ( Lamiaceae). These compounds have extensive applications as both effective and biocompatible bioactive agents for the treatment of various diseases including cardiovascular disorders, liver ailments, and neuroprotection. This study aimed to evaluate the skin-whitening effects of SAA and SAB on co-cultured human melanoma A375 cells and human keratinocytes HaCaT cells, with the intention of investigating their potential as cosmetic ingredients. Methods First, we assessed the SAA and SAB's efficacy on cells proliferation using MTT assay, as well as their inhibition on intracellular tyrosinase (TYR) activity. Next, we evaluated their effects on the mRNA expression levels of TYR and its related proteins. Furthermore, the whitening efficacy of SAA and SAB was assessed by observing the decrease in melanin content in treated human amalignant melanoma A375 and human keratinocyte HaCaT cells. Results Both SAA and SAB inhibited the activity of TYR and decreased the mRNA expression of TYR-related proteins, thereby inhibiting melanin synthesis. Conclusion Our results suggest that both SAA and SAB can be applied as natural and novel cosmetics materials having a whitening function, which could be beneficial in the cosmeceutical industry.

A novel Mutidrug and Toxic Compound Extrusion (MATE) gene SmMATE1 from Salvia miltiorrhiza Bunge, is involved in tetracycline induced mitochondrial toxicity adaptation synergically with salvianolic acid B

As a tetracycline antibiotic, the enrichment of doxycycline in soil seriously endangers agricultural cultivation and food security. Salvianolic acid B (SAB), as a natural product, has high antioxidant activity. We applied SAB and doxycycline (DOX) externally to Salvia miltiorrhiza seedlings, and measured the activities of total superoxide dismutase, peroxidase and catalase, as well as the accumulation of malondialdehyde, active oxygen and glutathione. It was found that SAB can participate in the DOX stress release of S. miltiorrhiza through the antioxidant system. We also analyzed the evolutionary relationship of multidrug and toxic compound extrusion (MATE) family proteins related to antibiotic transport in 50 representative evolutionary genomes, and revealed the potential binding ability of MATE and DOX through macromolecular docking. Finally, based on transcriptome and RT-qPCR analysis, we identified a novel gene SmMATE1, and found that it has a co-expression pattern with SmRAS and SmCYP98A14. Transgenic in tobacco, yeast and hairy root of S. miltiorrhiza revealed the important role of this new gene and SAB in synergistically releasing DOX stress damage, which provided a reference for natural product to alleviate the stress of antibiotics on plants, and also provided a theoretical basis for the development of new soil antibiotic sustained-release agents.

Inhibitory effects and mechanisms of low-temperature plasma on hypertrophic scar

Recent advancements in comprehending the properties of low-temperature plasmas (LTPs) have spurred the creation of plasma medicine. Nonetheless, there exists limited scientific evidence concerning its mechanism of impeding proliferative scarring. This study aims to investigate the role of LTPs in hypertrophic scar (HS) formation. Establishing rabbit ear scar models, two groups were individually treated with salvianolic acid B (SAB) gel and low-temperature plasmas for six weeks, while the control group was not treated. The expression levels of cytokines, including TGF-β1, p-Smad3, and MMP-2, in rabbit serum were assessed using ELISA in this study. Additionally, hematoxylin-eosin staining and Masson’s trichrome staining were conducted on proliferative scar tissue to observe the arrangement of collagen fibers and determine the density of fibroblasts. Immunohistochemical analysis was also performed to obtain the percentage of type I collagen and α-SMA positive expression area. The findings indicated that the scars in both the SAB and LTP groups were narrower than those in the model group. The scar tissues treated with LTP or SAB showed a lower level of TGF-β1 and p-Smad3. In addition, α-SMA was significantly reduced in the LTP-treated group. Furthermore, the type I collagen expression was lower in the LTP group. These results suggest that LTP could have a comparable effect to SAB in hindering the development of HSs. It could potentially enhance skin scarring by impeding collagen deposition and fibroblast proliferation in HSs via the TGF-β/Smad signaling pathway. This investigation may provide a new perspective on HS treatment.

Targeted delivery of hybrid nanovesicles for enhanced brain penetration to achieve synergistic therapy of glioma

Blood-brain barrier (BBB) obstructing brain drug delivery severely hampers the therapeutic efficacy towards glioma. An efficient brain delivery strategy is of paramount importance for the treatment of glioma. Inspired by brain targeting exosome, biomimetic BBB penetrated hybrid (pHybrid) nanovesicles, engineered by membrane fusion between blood exosome and tLyp-1 peptide modified liposome, is explored for brain targeting drug delivery. Transferrin receptor (TfR) on pHybrid nanovesicles facilitates the BBB transcytosis into brain parenchyma, and eventually endocytosed by glioma cells and diffusion to extra-vascular tumor tissues under the guidance of tLyp-1 peptide. pHybrid nanovesicles co-loaded with salvianolic acid B (SAB) and cryptotanshinone (CPT), which is constructed by membrane hybridization of blood exosome loaded with SAB and tLyp-1 modified liposome loaded with CPT, are explored for cytotoxic and anti-angiogenetic therapy towards glioma. Upon accumulation at tumor site, the loaded CPT and SAB shows synergistic effects towards glioma from cytotoxicity on cancer cells and anti-angiogenesis on tumor, respectively. Overall, this study provides a biomimetic nanoplatform for increased BBB transcytosis into brain parenchyma, which serves as a prospective strategy for delivering therapeutic agents against glioma through synergistic mechanisms.

Salvianolic acid B-loaded polydopamine-modified hollow mesoporous organic silica nanoparticles for treatment of breast cancer metastasis via suppressing cancer-associated fibroblasts

ObjectiveDrug Delivery System was constructed using dopamine-coated organic-inorganic hybrid hollow mesoporous organic silica nanoparticles (HMON-PDA) as drug carriers and salvianolic acid B (SAB) as a model drug. Then, we further investigated whether it can inhibit lung metastasis of breast cancer by inhibiting cancer-associated fibroblasts (CAFs). MethodsThe organic-inorganic hybrid hollow mesoporous organic silica nanoparticles (HMON) were prepared. The particle size, zeta potential, and polydispersion coefficient were characterized. High-performance liquid chromatography was used to determine the effect of different feed ratios of HMON and SAB on drug loading rate. Then, SAB-loaded HMON were modified by polydopamine, which is called SAB@HMON-PDA. Cell viability was detected by MTT assay. The migration of 4T1 cells was investigated by wound healing experiment, and the invasion of 4T1 cells was detected by the transwell method. Finally, the mouse breast cancer lung metastasis models were used to explore whether SAB@HMON-PDA can inhibit lung metastasis of breast cancer by inhibiting CAFs. ResultsThe obtained nanoparticles have hollow spherical structure. The average particle sizes of HMON, SAB@HMON, and SAB@HMON-PDA were 143.5 ± 0.03, 138.3 ± 0.02, and 172.3 ± 0.18 nm, respectively. The zeta potentials were -44.33±0.15, -41.4 ± 1.30, and -24.13±0.47 mV, respectively. When the ratio of HMON to SAB was 2:1, the drug loading rate reached (18.37±0.04)%. In addition, the prepared SAB@HMON-PDA responded to release SAB under acidic and GSH conditions. The prepared SAB@HMON-PDA could inhibit the migration and invasion of 4T1 cells. The results showed that SAB@HMON-PDA and SAB could inhibit lung metastasis of breast cancer in mice, and SAB@HMON-PDA had a more significant inhibitory effect than SAB. ConclusionWe successfully prepared SAB@HMON-PDA with the dual response of pH and GSH. SAB@HMON-PDA can inhibit the migration and invasion of 4T1 cells, and the effect is more significant than free SAB. This inhibitory effect may be related to the inhibition of CAFs. In vivo experiments demonstrated that SAB@HMON-PDA can inhibit lung metastasis of breast cancer by inhibiting CAFs, and its effect was more significant than that of free SAB.

Chitosan-salvianolic acid B coating on the surface of nickel-titanium alloy inhibits proliferation of smooth muscle cells and promote endothelialization.

Introduction: Intracranial stents are of paramount importance in managing cerebrovascular disorders. Nevertheless, the currently employed drug-eluting stents, although effective in decreasing in-stent restenosis, might impede the re-endothelialization process within blood vessels, potentially leading to prolonged thrombosis development and restenosis over time. Methods: This study aims to construct a multifunctional bioactive coating to enhance the biocompatibility of the stents. Salvianolic acid B (SALB), a bioactive compound extracted from Salvia miltiorrhiza, exhibits potential for improving cardiovascular health. We utilized dopamine as the base and adhered chitosan-coated SALB microspheres onto nickel-titanium alloy flat plates, resulting in a multifunctional drug coating. Results: By encapsulating SALB within chitosan, the release period of SALB was effectively prolonged, as evidenced by the in vitro drug release curve showing sustained release over 28days. The interaction between the drug coating and blood was examined through experiments on water contact angle, clotting time, and protein adsorption. Cellular experiments showed that the drug coating stimulates the proliferation, adhesion, and migration of human umbilical vein endothelial cells. Discussion: These findings indicate its potential to promote re-endothelialization. In addition, the bioactive coating effectively suppressed smooth muscle cells proliferation, adhesion, and migration, potentially reducing the occurrence of neointimal hyperplasia and restenosis. These findings emphasize the exceptional biocompatibility of the newly developed bioactive coating and demonstrate its potential clinical application as an innovative strategy to improve stent therapy efficacy. Thus, this coating holds great promise for the treatment of cerebrovascular disease.

Salvianolic acid B protects against pulmonary fibrosis by attenuating stimulating protein 1-mediated macrophage and alveolar type 2 cell senescence.

Idiopathic pulmonary fibrosis (IPF), as the most common idiopathic interstitial pneumonia, is caused by a complex interaction of pathological mechanisms. Interestingly, IPF frequently occurs in the middle-aged and elderly populations but rarely affects young people. Salvianolic acid B (SAB) exerts antioxidant, antiinflammatory, and antifibrotic bioactivities and is considered a promising drug for pulmonary disease treatment. However, the pharmacological effects and mechanisms of SAB on cellular senescence of lung cells and IPF development remain unclear. We used bleomycin (BLM)-induced pulmonary fibrosis mice and different lung cells to investigate the antisenescence impact of SAB and explain its underlying mechanism by network pharmacology and the Human Protein Atlas database. Here, we found that SAB significantly prevented pulmonary fibrosis and cellular senescence in mice, and reversed the senescence trend and typical senescence-associated secretory phenotype (SASP) factors released from lung macrophages and alveolar type II (AT2) epithelial cells, which further reduced lung fibroblasts activation. Additionally, SAB alleviated the epithelial-mesenchymal transition process of AT2 cells induced by transforming growth factor beta. By predicting potential targets of SAB that were then confirmed by chromatin immunoprecipitation-qPCR technology, we determined that SAB directly hampered the binding of transcription factor stimulating protein 1 to the promoters of SASPs (P21 and P16), thus halting lung cell senescence. We demonstrated that SAB reduced BLM-induced AT2 and macrophage senescence, and the subsequent release of SASP factors that activated lung fibroblasts, thereby dual-relieving IPF. This study provides a new scientific foundation and perspective for pulmonary fibrosis therapy.