Search Results (85)

Traumatic brain injury (TBI) is a major global health concern and a leading cause of long-term disability and mortality. While the primary mechanical insult is often the focus of acute care, secondary injury mechanisms—particularly cerebrovascular dysfunction—play a critical role in ongoing neural damage and poor outcomes. Increasing research highlights the role of neurovascular changes in TBI pathophysiology. This narrative review compiles evidence from the past decade on mechanisms, diagnostic methods, and treatments related to cerebrovascular dysfunction after TBI. A structured search of PubMed and Embase identified relevant clinical and preclinical studies. Key mechanisms include blood–brain barrier disruption, impaired cerebral autoregulation, microthrombosis, and oxidative stress. Diagnostic tools discussed include perfusion imaging, cerebrovascular reactivity testing, and blood-based biomarkers of vascular injury. Therapeutic strategies targeting the neurovascular unit are categorized by mechanism: anti-inflammatory agents (e.g., celecoxib, minocycline), mitochondrial protectors (e.g., Tanshinone IIA), and vasomodulators (e.g., sildenafil). We propose an integrated therapeutic approach for a multimodal treatment plan that integrates these interventions. The findings emphasize the importance of patient-specific vascular therapies to reduce secondary ischemic injury and enhance neurological recovery. Although promising preclinical data exist, clinical application remains limited. More well-designed trials are needed to confirm the safety and effectiveness of emerging therapies. Full article

Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and chronic hyperglycemia, markedly increases the incidence and mortality of cardiovascular disease (CVD). Emerging preclinical evidence identifies the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) pathway as a critical mediator of diabetic cardiovascular inflammation. Metabolic stressors in T2DM—hyperglycemia, lipotoxicity, and mitochondrial dysfunction—induce leakage of mitochondrial and microbial double-stranded DNA into the cytosol, where it engages cGAS and activates STING. Subsequent TBK1/IRF3 and NF-κB signaling drives low-grade inflammation across cardiomyocytes, endothelial cells, macrophages, and fibroblasts. Genetic deletion of cGAS or STING in high-fat-diet-fed diabetic mice reduces NLRP3 inflammasome-mediated pyroptosis, limits atherosclerotic lesion formation, and preserves cardiac contractile performance. Pharmacological inhibitors, including RU.521 (cGAS antagonist), C-176/H-151 (STING palmitoylation blockers), and the TBK1 inhibitor amlexanox, effectively lower pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and improve left ventricular ejection fraction in diabetic cardiomyopathy and ischemia–reperfusion injury models. Novel PROTAC degraders targeting cGAS/STING and natural products such as Astragaloside IV and Tanshinone IIA further support the pathway’s druggability. Collectively, these findings position the cGAS–STING axis as a central molecular nexus linking metabolic derangement to cardiovascular pathology in T2DM and underscore its inhibition or targeted degradation as a promising dual cardiometabolic therapeutic strategy. Full article

Tanshinone IIA (T-IIA), a fat-soluble diterpene quinone extracted from Salvia miltiorrhiza, is widely recognized for its multiple pharmacological properties, including anti-inflammatory, antioxidant, anti-fibrotic, and anti-tumor effects. Recent studies have highlighted its great potential in treating bone metabolic disorders, especially osteoporosis and bone damage repair. Bone health depends on the dynamic balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Disruption of this balance can lead to diseases such as osteoporosis, which is often diagnosed after a fracture, seriously affecting the quality of life and increasing the medical burden. Early identification of high-risk groups and appropriate treatment are essential for preventing fracture recurrence. Studies have shown that T-IIA can promote osteoblast differentiation and inhibit osteoclast activity, targeting key signaling pathways such as NF-κB, PI3K/Akt, and Wnt/β-catenin, all of which are closely related to bone metabolism. T-IIA has a dual role in regulating bone formation and bone resorption, making it a potential drug for the treatment of osteoporosis. In addition, T-IIA has neuroprotective, hepatic, renal, cardiac, and cerebral effects, which enhance its therapeutic effect. Despite the remarkable efficacy of T-IIA, its clinical application is limited due to poor solubility and low bioavailability. Recent advances in drug delivery systems, such as liposome formulations and nanocarriers, have improved their pharmacokinetics, increased absorption rate, and bioavailability. Combination therapy with growth factors or stem cells can further enhance its efficacy. Future studies should focus on optimizing the delivery system of T-IIA and exploring its combined application with other therapeutic strategies to expand its clinical application range. Full article

Tanshinones are a class of lipophilic diterpenoid quinones extracted from Salvia miltiorrhiza (Dan shen), a widely used herb in traditional Chinese medicine. These compounds, particularly tanshinone IIA (T-IIA) and sodium tanshinone sulfonate (STS), have been acknowledged for their broad spectrum of biological activities, including anti-inflammatory, antioxidant, anti-tumor, antiresorptive, and antimicrobial effects. Recent studies have highlighted the potential of tanshinones in the treatment of osteolytic diseases, characterized by excessive bone resorption, such as osteoporosis, rheumatoid arthritis, and periodontitis. The therapeutic effects of tanshinones in these diseases are primarily attributed to their ability to inhibit osteoclast differentiation and activity, suppress inflammatory cytokine production (e.g., tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6), and modulate critical signaling pathways, including NF-kB, MAPK, PI3K/Akt, and the RANKL/RANK/OPG axis. Additionally, tanshinones promote osteoblast differentiation and mineralization by enhancing the expression of osteogenic markers such as Runx2, ALP, and OCN. Preclinical models have demonstrated that T-IIA and STS can significantly reduce bone destruction and inflammatory cell infiltration in arthritic joints and periodontal tissues while also enhancing bone microarchitecture in osteoporotic conditions. This review aims to provide a comprehensive overview of the pharmacological actions of tanshinones in osteolytic diseases, summarizing current experimental findings, elucidating underlying molecular mechanisms, and discussing the challenges and future directions for their clinical application as novel therapeutic agents in bone-related disorders, especially periodontitis. Despite promising in vitro and in vivo findings, clinical evidence remains limited, and further investigations are necessary to validate the efficacy, safety, and pharmacokinetics of tanshinones in human populations. Full article

Salvia miltiorrhiza is a traditional herbal remedy for cardiovascular diseases and is in high demand in the market. Excessive chemical fertilizer application, resulting from unscientific fertilization practices, reduced the tanshinone content in S. miltiorrhiza roots. This study investigated how different fertilization types alter the endophytic microbial community composition of S. miltiorrhiza through field experiments, aiming to understand how fertilization affects its medicinal quality. The results showed that root fertilizers (F1) significantly increased root biomass and tanshinone I content, whereas foliar fertilizers (F2) increased tanshinone IIA content. High-throughput sequencing further revealed that F2 treatment significantly decreased the Shannon index of endophytic bacteria while significantly increasing the Shannon index of endophytic fungi. Co-occurrence network analysis revealed that fertilization significantly altered fungal community complexity and modularity, with F1 increasing network nodes and edges. Variance partitioning analysis indicated fungal diversity more strongly influenced medicinal compound levels under F2 and a combination of both (F3) than bacterial diversity. Septoria and Gibberella were positively correlated with tanshinone I and cryptotanshinone content under F2 treatment, respectively. Notably, the unique strains were isolated from different fertilization treatments for subsequent bacterial fertilizer development. These findings elucidate microbial responses to fertilization, guiding optimized cultivation for improved S. miltiorrhiza quality. Full article

Ferruginol, tanshinones and carnosol are considered privileged natural products due to their demonstrated diverse biological activities with relevance to cancer research. Globally, cancer continues to be a major contributor to mortality rates, making these compounds potentially valuable molecular scaffolds for further development as potential anticancer agents. In this work, a focused library of ferruginol, tanshinone IIA, and carnosol analogues was studied to examine their effectiveness against various solid tumor models. The compounds were efficiently synthesized from either methyl 12-hydroxy-dehydroabietate or 12-hydroxydehydroabietylamine in 1–3 step processes with good chemical yields. The compounds that were synthesized underwent a methodical evaluation using multiple biological tests (including viability assays, clonogenic assays, and mitochondrial membrane polarization measurements) to determine their ability to inhibit in vitro the growth of three breast cancer cell linages. It was determined that while most compounds exhibited biological activity, compounds 10 and 11 demonstrated significant efficacy against triple negative breast cancer cells. These compounds continue to show promising biological activity, suggesting that additional studies to understand their mechanisms of action would be valuable. Full article

Background: Early studies indicated that the high content of tanshinone IIA (T−IIA) and rosmarinic acid (RA) in Salvia castanea Diels f. Tomentosa Stib (SCT) gives them significant potential for development as therapeutic agents for ischemic stroke (IS). However, the extraction process and quality of the active ingredients from SCT are still big challenges, with present processes providing insufficient pharmacological effects. This study aims to identify the optimal extraction process and perform a quality characterization of the total tanshinones and phenolic acids extracted from SCT, as well as to elucidate the neuroprotective effect of these extracts. Methods: The extraction process was optimized using an orthogonal experimental design (OED), and quality characterization was performed using HPLC, UV, and LC-MS. The neuroprotective effect of the extracted tanshinones and phenolic acids was studied using the middle cerebral artery occlusion (MCAO) paradigm, and its underlying mechanism was revealed through RNA-seq analysis combined with network pharmacology. Results: The optimal extraction pressure of total tanshinones was 60 MPa, while the extraction temperature and time for total phenolic acids were 4 °C and 25 min, respectively. In these extracts, the total tanshinone and phenolic acid contents increased to 369.43 and 189.10 mg/g, respectively; 23 of the 19 tanshinones and 23 phenolic acids identified in this study have not been observed in previous studies. It was demonstrated that the combined extract had a promising neuroprotective effect against IS; RNA-seq combined with network pharmacology analysis indicated that the active compounds may regulate a series of core genes associated with signaling pathways to protect against IS. Conclusions: The combined SCT extract studied in this research exerted neuroprotective effects on IS. In general, these findings improve our preliminary understanding of the chemical composition and bioactivity of SCT. Full article

Objectives: This research aims to explore the therapeutic potential of Bi-Qi capsules in the treatment of gout by identifying crucial drug targets through a multidimensional data analysis strategy. Methods: Bi-Qi capsule drug targets and differentially expressed genes (DEGs) of gout were derived from public databases, such as Swiss Target Prediction, STITCH, and the GEO database. Subsequently, the overlapped targets were analyzed to elucidate the potential therapeutic mechanism and to identify candidate targets of Bi-Qi capsules against gout. Next, Mendelian randomization (MR) analysis was employed to screen and explore the causal relationship between candidate targets and gout. Finally, single-cell RNA sequencing (scRNA-seq), gene set enrichment analysis (GSEA), transcription factor and ceRNA regulatory networks, and molecular docking were performed to validate the role of the crucial targets of Bi-Qi capsules in the treatment of gout. Results: A total of 46 candidate targets were identified, in which KCNA5, PTGS2, and TNF exhibited significant causal relationships with gout (p < 0.05) and were regarded as the crucial targets. Through scRNA-seq and gene labeling, crucial targets were found to be expressed in eighteen cell clusters and eight cell types, which are closely associated with carbohydrate metabolism, nerve conduction, and the innate immunity process. Bi-Qi capsule active compounds such as tanshinone IIA, strychnine, tanshinaldehyde, cryptotanshinone, tumulosic acid, and glycyrrhetic acid exhibit a better binding ability to crucial targets. Conclusions: The results not only elucidate the anti-gout mechanism of Bi-Qi capsules but also provide an insight into multi-target natural medication for metabolic disease treatment, which contributes to guiding the clinical application of Bi-Qi capsules in the future. Full article

Background: This is a comparative metabolomic study of the medicinal plant Dryopteris fragrans (L.) Schott from the family Dryopteridaceae Herter (or Aspidiaceae Mett. ex Frank) growing under cold pole conditions in the Oymyakon region of the Republic of Sakha (Yakutia). Methods: The aerial parts of D. fragrans were subjected to extraction using supercritical CO₂ extraction and maceration methods. Several experimental conditions were investigated, including a pressure range of 50–300 bar and a temperature range of 31–60 °C. A 1% volume of ethanol was used as a co-solvent in the liquid phase of the extraction. Results: The most effective D. fragrans extraction conditions were 200 Bar pressure and a temperature of 55 °C. Tandem mass spectrometry was used to detect the target analytes. A total of 141 bioactive compounds (86 compounds from the polyphenol group and 55 compounds from other chemical groups) were tentatively identified in extracts of aerial parts of D. fragrans. Among these, thirty chemical constituents from the polyphenol group were identified for the first time. Other compound classes that were newly identified in D. fragrans include naphthoquinones (5,8-dihydroxy-6-methyl-2,3-dihydro-1,4-naphthoquinone, 1,8-dihydroxy-anthraquinone, 1,4,8-trihydroxyanthraquinone, chrysophanol, etc.), diterpenoids (tanshinone IIa, cryptotanshinone, isocryptotanshinone II, tanshinone IIb, etc.), polysaccharides, triterpenoids, and sesquiterpenes. Conclusions: These results highlight that D. fragrans is rich in bioactive compounds and put forward several newly detected compounds for further investigation. Full article

Background: XueBiJing injection (XBJ) is renowned for its multi-target pharmacological effects, including immunomodulatory, antithrombotic, and antioxidant activities, offering potential therapeutic benefits for patients with severe infections such as sepsis and Coronavirus disease 2019 (COVID-19). Despite its clinical effectiveness, the molecular targets and mechanisms of XBJ remain unclear, warranting further investigation. Purpose: This study aimed to identify the key bioactive compounds in XBJ and elucidate their molecular targets and mechanisms. Methods: The zebrafish model was first used to evaluate the anti-inflammatory and antioxidant effects of XBJ, and the differentially expressed genes (DEGs) were identified by RNA sequencing and network analysis. Network pharmacology was used to analyze the relationship between bioactive compounds and molecular targets, and molecular docking and kinetic simulation were used to explore the target binding ability of key compounds. Cellular Thermal Shift Assay-Western Blot (CETSA-WB) and Surface Plasmon Resonance (SPR) further verified the interaction between compounds and targets; finally, the key pathways were confirmed by gene silencing experiments. Results: The zebrafish model results reveal that XBJ significantly reduced neutrophil and macrophage counts in a dose-dependent manner, emphasizing its potent anti-inflammatory effects. A transcriptomic analysis highlighted the differential expression of key genes in the KEAP1/NRF2 pathway, including HMOX1, SLC7A11, NQO1, and TXNRD1. A network analysis further pinpointed KEAP1 as a central molecular target, with tanshinone IIA, baicalein, and luteolin identified as key active compounds modulating this pathway. Among these, tanshinone IIA and baicalein exhibited strong binding interactions with KEAP1, which were confirmed through molecular docking and kinetic simulations. Further validation showed that baicalein directly targets KEAP1, as demonstrated by CETSA-WB and SPR analysis. Additionally, the gene silencing experiments of KEAP1 and NRF2 reinforced their crucial roles in activating the KEAP1/NRF2 pathway. Conclusion: These findings collectively establish baicalein as a critical bioactive compound in XBJ, driving its antioxidant and anti-inflammatory effects via KEAP1/NRF2 pathway activation through direct binding to KEAP1, providing new insights into the mechanism of action of XBJ. Full article

Background: Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of Salvia miltiorrhiza Bunge (Danshen), a common Chinese medicinal herb. However, clinical applications of Tan IIA are limited due to its poor solubility in water. Methods: To overcome this limitation, we developed a calcium alginate hydrogel (CA) as a hydrophilic carrier for Tan IIA, which significantly improved its solubility. We also prepared nanoparticles with pH-responsive properties to explore their potential for controlled drug delivery. The physicochemical properties of Tan IIA/CA nanoparticles were evaluated, including their size, stability, and release profile. We also utilized RNA sequencing to further investigate the underlying anticancer mechanisms of Tan IIA/CA nanoparticles. Results: The Tan IIA/CA nanoparticles demonstrated enhanced solubility and exhibited potent anticancer activity in vitro. Additionally, the nanoparticles showed promising pH-responsive behavior, which is beneficial for controlled release applications. Further investigation into the molecular mechanisms revealed that the anticancer effects of Tan IIA/CA were mediated through apoptosis, ferroptosis, and autophagy pathways. Conclusions: This study confirms the anticancer potential and mechanisms of Tan IIA, while also presenting an innovative approach to enhance the solubility of this poorly soluble compound. The use of CA-based nanoparticles could be a valuable strategy for improving the therapeutic efficacy of Tan IIA in cancer treatment. Full article

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays. W12 cells, derived from a cervical precancerous lesion, contain either episomal or integrated HPV16 DNA. Several compounds, including digoxin, tanshinone IIA, dihydromethysticin and carrageenan, as well as fractions of turmeric, ginger and pomegranate inhibited the growth of W12 precancer and cervical cancer cells. Curcumin and tanshinone IIA were the most active and relatively nontoxic compounds. RT-PCR analysis showed that tanshinone IIA activated the expression of p53, while repressing the expression of HPV16 E1, E2, E4, E6, and E7 viral transcripts in W12 (type 1 and 2) integrant cells. In addition, curcumin synergized with tanshinone IIA in HeLa cells. Molecular docking studies suggested tanshinone IIA and curcumin bind to the Na⁺/K⁺-ATPase ion channel, with curcumin binding with higher affinity. Our findings highlight the potential of these multifaceted phytochemicals to prevent and treat HPV-induced cervical cancer, offering a promising approach for combinatorial therapeutic intervention. Full article

Prolactinomas are commonly treated with dopamine receptor agonists (DAs), such as bromocriptine (BRC) and cabergoline (CAB). However, 10–30% of patients exhibit resistance to DA therapies. DA resistance is largely associated with reduced dopamine D2 receptor (DRD2) expression, potentially regulated by epigenetic modifications, though the underlying mechanisms are still unclear. Clinical samples were assessed for p300 expression. MMQ and AtT-20 cells were engineered to overexpress either wild-type p300 or a histone acetyltransferase (HAT) domain-mutant form of p300. Mechanistic studies included cell proliferation assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, chromatin immunoprecipitation followed by quantitative PCR, reverse transcription quantitative PCR, and Western blotting. Additionally, an in vivo nude mouse xenograft model was used to confirm the in vitro findings. DAs downregulated p300 through the cAMP-PKA-CREB pathway. Activation of the HAT domain of p300 increased H3K18/27 acetylation, promoted DRD2 transcription, and worked synergistically with DA to exert anti-tumor effects both in vitro and in vivo. Tanshinone IIA (Tan IIA) upregulated p300 and DRD2, enhancing the therapeutic efficacy of BRC. These findings highlight the role of p300 in regulating DRD2 transcription in DA-resistant prolactinomas. Combining Tan IIA with BRC may offer a promising strategy to overcome DA resistance. Full article

Hyperspectral imaging (HSI) technology was combined with chemometrics to achieve rapid determination of tanshinone contents in Salvia miltiorrhiza, as well as the rapid identification of its origins. Derivative (D1), second derivative (D2), Savitzky–Golay filtering (SG), multiplicative scatter correction (MSC), and standard normal variate transformation (SNV) were utilized to preprocess original spectrum (ORI). Partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM) models were employed to discriminate 420 Salvia miltiorrhiza samples collected from Shandong, Hebei, Shanxi, Sichuan, and Anhui Provinces. The contents of tanshinone IIA, tanshinone I, cryptotanshinone, and total tanshinones in Salvia miltiorrhiza were predicted by the back-propagation neural network (BPNN), partial least square regression (PLSR), and random forest (RF). Finally, effective wavelengths were selected using the successive projections algorithm (SPA) and variable iterative space shrinkage approach (VISSA). The results indicated that the D1-PLS-DA model performed the best with a classification accuracy of 98.97%. SG-BPNN achieved the best prediction effect for cryptotanshinone (RMSEP = 0.527, RPD = 3.25), ORI-BPNN achieved the best prediction effect for tanshinone IIA (RMSEP = 0.332, RPD = 3.34), MSC-PLSR achieved the best prediction effect for tanshinone I (RMSEP = 0.110, RPD = 4.03), and SNV-BPNN achieved the best prediction effect for total tanshinones (RMSEP = 0.759, RPD = 4.01). When using the SPA and VISSA, the number of wavelengths was reduced below 60 and 150, respectively, and the performance of the models was all very good (RPD > 3). Therefore, the combination of HSI with chemometrics provides a promising method for predicting the active ingredients of Salvia miltiorrhiza and identifying its geographical origins. Full article

Intracranial aneurysms, characterized by abnormal dilations of cerebral arteries, pose significant health risks due to their potential to rupture, leading to subarachnoid hemorrhage with high mortality and morbidity rates. This paper aim is to explore the innovative application of nanoparticles in treating intracranial aneurysms, offering a promising avenue for enhancing current therapeutic strategies. We took into consideration the pathophysiology of cerebral aneurysms, focusing on the role of hemodynamic stress, endothelial dysfunction, and inflammation in their development and progression. By comparing cerebral aneurysms with other types, such as aortic aneurysms, we identify pathophysiological similarities and differences that could guide the adaptation of treatment approaches. The review highlights the potential of nanoparticles to improve drug delivery, targeting, and efficacy while minimizing side effects. We discuss various nanocarriers, including liposomes and polymeric nanoparticles, and their roles in overcoming biological barriers and enhancing therapeutic outcomes. Additionally, we discuss the potential of specific compounds, such as Edaravone and Tanshinone IIA, when used in conjunction with nanocarriers, to provide neuroprotective and anti-inflammatory benefits. By extrapolating insights from studies on aortic aneurysms, new research directions and therapeutic strategies for cerebral aneurysms are proposed. This interdisciplinary approach underscores the potential of nanoparticles to positively influence the management of intracranial aneurysms, paving the way for personalized treatment options that could significantly improve patient outcomes. Full article