Search Results (254)

Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, which possesses diverse pharmacological activities. This study aims to investigate the effect and mechanisms of SAL-A in inhibiting ferroptosis to improve ischemic stroke. Brain injury, oxidative stress and ferroptosis-related analysis were performed to evaluate the effect of SAL-A on ischemic stroke in photochemical induction of stroke (PTS) in mice. Lipid peroxidation levels, antioxidant protein levels, tissue iron content, nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial morphology changes were detected to explore its mechanism. SAL-A significantly attenuated brain injury, reduced malondialdehyde (MDA) and long-chain acyl-CoA synthase 4 (ACSL4) levels. In addition, SAL-A also amplified the antioxidative properties of glutathione (GSH) when under glutathione peroxidase 4 (GPX4), and the reduction in ferrous ion levels. In vitro, brain microvascular endothelial cells (b.End.3) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate whether the anti-stroke mechanism of SAL-A is related to Nrf2. Following OGD/R, ML385 (Nrf2 inhibitor) prevents SAL-A from inhibiting oxidative stress, ferroptosis, and mitochondrial dysfunction in b.End.3 cells. In conclusion, SAL-A inhibits ferroptosis to ameliorate ischemic brain injury, and this effect is mediated through Nrf2. Full article

Red sage (Salvia miltiorrhiza Bunge) is a perennial herb containing various bioactive compounds that promote human health. In this study, single-factor experiments were first conducted, followed by the optimization of extraction conditions to maximize the saponin content from red sage root extracts. In the single-factor experiments, the highest saponin content (47.5 ± 0.88 mg/g) was obtained using 80% ethanol, a solvent-to-material ratio of 40:1 (mL/g), an extraction period of 3 h, and an extraction temperature of 60 °C. Response Surface Methodology (RSM) was performed to optimize the extraction parameters with a material-to-solvent ratio of 41.31:1 (mL/g), an extraction temperature of 58.08 °C, and an extraction time of 3.16 h. Under these optimized conditions, the experimental saponin content reached 47.71 ± 0.15 mg/g. Additionally, crude extract of red sage exhibited antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals with an IC₅₀ value of 16.24 µg/mL. This extract also demonstrated anticancer against 61.79 ± 3.57% HepG2 cancer cells at a concentration of 100 µg/mL. 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

Phosphorus (P), as one of the essential bulk elements for plant growth and development, plays an important role in root growth, accumulation of secondary metabolites, and regulation of gene expression. In Salvia miltiorrhiza Bunge (S. miltiorrhiza), an important medicinal plant, the accumulation of its active components is closely related to the level of phosphorus supply, but the molecular regulatory mechanism of phosphorus treatment in the growth and secondary metabolism of S. miltiorrhiza is not clear. In this study, we investigated the effects of low phosphorus (P2), moderate phosphorus (P4), and high phosphorus (P6) treatment on the growth and development of S. miltiorrhiza. seedlings, the accumulation of bioactive compounds, and their transcriptional regulation using transcriptomic and metabolomic analyses, and identified the key regulatory genes in the biosynthesis pathways of tanshinone and salvianolic acid. The findings revealed that S. miltiorrhiza biomass exhibited a “peaked” response to phosphorus concentration, peaking at 0.625 mmol·L⁻¹. At this optimal concentration, all four batches achieved maximum root length, root weight, and leaf weight: Batch I (11.3 cm, 2.34 g, 1.62 g), Batch II (12.7 cm, 2.67 g, 1.89 g), Batch III (13.8 cm, 2.85 g, 2.04 g), and Batch IV (15.6 cm, 3.51 g, 2.44 g). Both lower and higher concentrations resulted in growth inhibition and reduced bioactive compound accumulation. Transcription factors associated with root growth and development included bHLH, MYB, and WRKY; in particular, the bZIP23 transcription factor was highly expressed under abnormal phosphorus supply conditions. In addition, the biosynthetic pathways of tanshinone and salvianolic acid were elucidated, and key genes related to the synthesis pathways (CPS, KSL, CYP, PAL, HPPR, and RAS) were identified. The expression of several TFs (such as SmCPS1, SmCYP76AH3, SmCYP76AH1, SmGGPPS1, and SmRAS1) was found to be correlated with tanshinone and salvianolic acid synthesis. The present study provides a theoretical basis for further revealing the molecular mechanism of phosphorus regulation of growth, development, and secondary metabolism of S. miltiorrhiza and provides potential targets for efficient cultivation and molecular breeding of S. miltiorrhiza. Full article

Background/Objectives: Allergens can trigger severe immune responses in hypersensitive individuals, with mast cells releasing inflammatory mediators via IgE-FcɛRI signaling. Spleen tyrosine kinase (Syk) is a key regulator in this pathway, making it a promising therapeutic target. Natural modulators of Syk-mediated mast cell activation remain underexplored. This study investigated the anti-allergic effects of a 70% ethanol extract of Salvia miltiorrhiza (SME) using in vitro and in vivo models. Methods: SME was evaluated using IgE-sensitized RBL-2H3 cells, a passive cutaneous anaphylaxis model, and a DNCB-induced atopic dermatitis-like mouse model. Allergic responses were assessed via degranulation assays, histopathology, serum IgE levels, and the spleen index. Results: SME significantly inhibited mast cell degranulation by 44.4 ± 1.6% in RBL-2H3 cells at 100 µg/mL following 30 min of treatment compared to the untreated control. Western blot analysis demonstrated dose-dependent suppression of protein kinase B (PKB, also known as AKT), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and spleen tyrosine kinase (Syk) phosphorylation, indicating inhibition of key allergic signaling pathways. In an IgE/Ag-induced passive cutaneous anaphylaxis model in ICR mice, SME (100 mg/kg, orally) significantly attenuated vascular permeability, as evidenced by a 20.6 ± 9.7% reduction in Evans blue extravasation relative to the Ag-treated group. In a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD)-like model, six treatments of SME significantly improved the skin condition, reduced spleen enlargement associated with allergic inflammation, and decreased serum IgE levels by 43.3 ± 11.2% compared to the DNCB group. Conclusions: These findings suggest that SME may help to alleviate allergic responses and AD by modulating key immune signaling pathways. 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

Gut microbiota dysbiosis is intricately linked to metabolic disorders such as obesity, type 2 diabetes mellitus (T2DM), hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD). Traditional Chinese medicine (TCM), particularly when combined with probiotic fermentation, offers a promising therapeutic strategy by modulating microbial balance and host metabolism. This narrative review synthesizes current research on probiotic-fermented herbal bioactives, focusing on their mechanisms in ameliorating metabolic diseases. Probiotic and bioactive compounds (e.g., berberine, polysaccharides) are highlighted for their roles in enhancing intestinal barrier function, regulating microbial metabolites like short-chain fatty acids (SCFAs), and reducing inflammation. Fermentation techniques improve the bioavailability of TCM components while reducing toxicity, as seen in fermented Salvia miltiorrhiza and Rhizoma Coptidis. Despite promising results, challenges include the complexity of microbiota–host interactions and variability in TCM standardization. Future directions emphasize integrating multi-omics technologies and personalized approaches to optimize probiotic-fermented TCM therapies. This review underscores the potential of combining traditional herbal wisdom with modern biotechnology to address metabolic disorders, which pose significant global health challenges, through a “gut microbiota–metabolism” axis. Emerging evidence highlights the critical role of gut microbiota dysbiosis in the pathogenesis of these conditions. TCM has shown promise in modulating gut microbiota to restore metabolic homeostasis. This review synthesizes current research on TCM-derived interventions, such as herbal compounds, probiotics, and fermentation techniques, that target gut microbiota to ameliorate metabolic disorders. We discuss mechanisms of action, including prebiotic effects, enhancement of intestinal barrier function, and regulation of microbial metabolites, while addressing the limitations and future directions of TCM-based therapies. Full article

Breast cancer remains a leading global cause of cancer-related mortality among women, requiring the development of safer and more effective therapeutic strategies. Herbal medicines have gained increasing attention as complementary approaches due to their multi-targeted actions, more limited toxicities, and the potential ability to overcome resistance associated with conventional treatments. This review highlights the antitumor properties and underlying mechanisms of several well-studied herbal compounds, including curcumin, resveratrol, epigallocatechin gallate, withaferin A, thymoquinone, baicalin, berberine, Oldenlandia diffusa, and Salvia miltiorrhiza. These phytochemicals exert antitumor effects by inducing apoptosis, inhibiting cell proliferation and metastasis, modulating immune responses, and sensitizing tumor cells to chemotherapy and radiotherapy. Furthermore, many of these agents regulate key signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells, phosphatidylinositol 3-kinase/AKT, p53, signal transducer and activator of transcription 3, and extracellular signal-regulated kinases 1/2, and the tumor microenvironment. Despite promising preclinical and early clinical evidence, challenges remain regarding the bioavailability, standardization, and large-scale clinical validation of these phytochemicals. This review underscores the therapeutic potential of herbal medicines in breast cancer treatment and advocates for further research to facilitate their integration into evidence-based oncology practice. Full article

YTH domain-containing proteins act as the primary readers of N⁶-methyladenosine (m⁶A), playing an important role in plant development and stress responses. However, little is known about the YTH proteins in medicinal plants. Genome-wide identification of the YTH gene family in the medicinal model plant, Salvia miltiorrhiza Bunge, identified a total of nineteen SmYTH genes from five chromosomes, with SmYTH8–SmYTH19 clustered on chromosome 8. Phylogenetic analysis showed that SmYTH proteins belong to the YTHDF category. No YTHDC members were identified. Conserved domain identification, amino acid sequence alignment, and phase separation prediction revealed that SmYTH1–SmYTH4 exhibited the characteristic m⁶A reader protein feature, containing conserved aromatic cages (WWW) capable of binding m⁶A residues. SmYTH5–SmYTH19 proteins contain a unique conserved F-box protein interaction domain that has not been reported previously. qRT-PCR analysis revealed tissue-specific patterns, with SmYTH1–SmYTH4 genes highly expressed in roots and leaves, whereas SmYTH8–SmYTH19 were mainly expressed in leaves. The results were consistent with RNA-seq data. The expression of various SmYTHs and the content of phenolic acid active ingredients were significantly altered under MeJA and SA treatments. The results provide useful information for further studies on the biological functions of m⁶A and YTH proteins in S. miltiorrhiza. Full article

There is an urgent need for novel therapeutics to combat Plasmodium falciparum, especially in light of increasing drug resistance. Here, we present a multiplexed native mass spectrometry (MS) platform capable of simultaneously screening multiple protein targets against chemically diverse crude extracts with minimal sample preparation. A mixture of seven malarial proteins was analyzed under optimized native MS conditions, enabling the detection of specific ligand binding events. Using this platform, lithospermate B from Salvia miltiorrhiza (Danshen) was identified as a novel ligand for a malarial ubiquitin-conjugating enzyme with moderate affinity (Kd = 30.5 ± 2.5 μM). This is the first report linking lithospermate B to a malarial protein target, highlighting the potential of native MS to uncover new bioactivities of known natural products. This approach significantly enhances the throughput of protein–ligand screening and offers a powerful tool for early-stage natural product-based drug discovery. Full article

Mining valuable genes is helpful to breed high-quality Salvia miltiorrhiza exhibiting efficient nitrogen fertilizer utilization efficiency. In the present study, transcriptome sequencing was introduced to select the candidate transcription factors (TFs) involved in tanshinones’ (TAs) and phenolic acids’ (PHAs) biosynthesis as well as low nitrogen (LN) stress. In totally, 97.71 Gb clean data was obtained from fifteen sequencing samples and 30,975 unigenes were assembled. Among of them, 27,843 unigenes were successfully annotated. Overall, 8663 differential expression genes (DEGs) were identified, among of which 5034 unigenes were up-regulated, and 3629 unigenes were down-regulated. By enrichment of DEGs together with gene co-expression network construction, 10 candidate TFs including HSFB2b, LBD12, ERF1A, ERF98, LBD25, HSF24, RAM1, HSFA4B, TCP8, and WRKY24 were finally retrieved, which are predicted to participate in modulating TA and PHA biosynthesis under LN stress. Quantitative real-time polymerase chain reaction (qRT-PCR) detection was introduced to further detect the expression profile of candidate TFs under LN stress. These findings offer a valuable resource for in-depth study of TAs ‘and PHAs’ biosynthesis under LN stress in S. miltiorrhiza. Full article

Metabolic syndrome, a cluster of metabolic disorders comprising dyslipidemia, insulin resistance, elevated blood pressure, and abdominal obesity, is a silent epidemic that may lead to outcomes such as cardiovascular disease, diabetes, and cancer. Due to the increase in the prevalence of these pathologies, the search for better treatments and more efficient drugs is imperative. Species of Artemisia and Salvia genera are excellent examples of noteworthy sources of bioactive products with health applications, their therapeutic properties being well known both in popular medicine and in the scientific community. There are reports of plant extracts or compounds from species belonging to either of these genera, which were able to combat cancer, diabetes, and cardiovascular pathologies. For instance, dihydroartemisinin (analog of artemisin extracted from Artemisia annua L.) can reduce tumor markers p53 and Ki-67 expression levels, leading to a reduction in tumor proliferation. Salvia officinalis L. has antihyperglycemic and lipid profile-improving effects since it decreases total cholesterol, glycosylated hemoglobin, fasting glucose, low-density lipoprotein cholesterol, and triglyceride levels while increasing high-density lipoprotein cholesterol levels. Clinical trials using mixtures (dried powdered plants or extracts) of known medicinal plants are recurrent in published works, in contrast with the scarce clinical trial studies with isolated compounds. Salvia miltiorrhiza Bunge. was by far the most targeted plant in the clinical trials analyzed here. Regarding clinical trials concerning Artemisia, there are more studies aiming to see its effect on diabetes, but the studies about cancer are more advanced. This review aims to give a critical summary of the most interesting and promising results from clinical trials. The abundance of studies with limited statistically significant clinical evidence hinders progress in clinical therapy. This situation demands far greater rigor from the scientific community, researchers, regulatory agencies, editors, and reviewers in conducting and publishing clinical studies. Full article

Acute myocardial infarction is an ischemic injury of the myocardium caused by an imbalance in the blood supply to myocardial tissues, which poses a serious threat to human life and health. Oxidative stress has been recognized as a significant contributor to acute myocardial infarction. Salvia miltiorrhiza Carbonisata (SMC) is among the most frequently employed herbal remedies for the treatment of acute myocardial infarction; however, the exact identity of its principal active constituents is not well defined. Research indicates that carbon dots (CDs) exhibit significant biological properties. Consequently, we initially synthesized carbon dots (CDs) from Salvia miltiorrhiza Carbonisata, with the objective of exploring how SMC-CDs mitigate isoproterenol (ISO)-induced myocardial infarction (MI) in rats. The results showed that the pretreatment with SMC-CDs markedly enhanced compromised cardiac function, mitigated myocardial fibrosis and the infiltration of inflammatory cells, decreased the size of the infarct, and suppressed cardiomyocyte apoptosis. Furthermore, the antioxidant properties of myocardial tissue were enhanced, and oxidative stress caused by free radicals was effectively mitigated by SMC-CDs, which succeeded in reducing levels of myocardial enzymes and elevating the activity of relevant ATPases. This implies that SMC-CDs could be a potential candidate for novel nanomedicine strategies designed to address cardiovascular ailments. Full article

Salvia miltiorrhiza is a herbaceous plant that possesses significant medicinal value. Land salinization affects the growth of S. miltiorrhiza, resulting in a decline in its quality and yield. Knotted1-like homeobox (KNOX) genes are transcription factors that play important roles in plant growth and abiotic stress. The characteristics and functions of KNOX genes in S. miltiorrhiza remain unclear. Here, we identified ten KNOX genes in S. miltiorrhiza, all of which possess the characteristic four domains: KNOX1, KNOX2, ELK, and HD. These SmKNOXs were divided into two groups together with homologous genes. Cis-acting element analysis indicated all SmKNOXs contained elements associated with phytohormone, light, and stress response. The SmKNOXs show tissue-specific expression among roots, stems, leaves, and flowers. We assessed the response of the SmKNOXs to salt stress using quantitative RT-PCR analysis. Notably, SmKNOX4 expression significantly decreased within 24 h of salt exposure, while SmKNOX1, SmKNOX2, SmKNOX3, SmKNOX8, and SmKNOX9 showed significant increases. The expression of SmKNOX1, SmKNOX2, and SmKNOX3 was significantly positively correlated with that of their target genes, GA20ox1 and S11 MYB. These findings suggest that SmKNOXs and their target genes respond to salt stress, providing a foundation for studies of SmKNOXs and the potential genetic improvement of S. miltiorrhiza. Full article

Hair loss is one of the skin conditions that can affect people’s mental health. Plant raw material extracts are of great interest due to their safety. In this study, we utilize reverse network pharmacology to screen for key targets of the Wnt/β-catenin signaling pathway and the TGFβ/BMP signaling pathway, as well as key differential lipids, for plant raw materials selection. The aim is to identify plant raw materials that may have anti-hair loss properties and to validate these findings through cell experiments. Licorice, salvia miltiorrhiza, mulberry leaf, ephedra and curcumae radix were found that may possess anti-hair loss effects. Licorice water extract (LWE), salvia miltiorrhiza water extract (SMWE), mulberry leaf water extract (MLWE), ephedra water extract (EWE) and curcumae radix water extract (CRWE) did not exhibit cytotoxicity on human dermal papilla cells (HDPCs). Through ALP staining, it was found that the expression of ALP in HDPCs treated with LWE, SMWE, MLWE, EWE and CRWE was enhanced. In addition, LWE, SMWE, MLWE, EWE and CRWE have reduced the expression of hair growth inhibitory factor TGF-β1 and inflammatory factor IL-6. Additionally, various water extracts can enhance the secretion of VEGF, with high concentrations of SMWE, EWE and CRWE exhibiting better efficacy. Furthermore, β-catenin, a key factor of the Wnt/β-catenin signaling pathway, was enhanced by LWE, SMWE, MLWE, EWE and CRWE treatment in cultured HDPCs. In conclusion, all five plant raw materials showed some anti-hair loss potential, providing theoretical support for their application in anti-hair loss products. Full article