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1.
Life Sci Alliance ; 6(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36319062

RESUMO

Ferroptosis is triggered by the breakdown of cellular iron-dependent redox homeostasis and the abnormal accumulation of lipid ROS. Cells have evolved defense mechanisms to prevent lipid ROS accumulation and ferroptosis. Using a library of more than 4,000 bioactive compounds, we show that tanshinone from Salvia miltiorrhiza (Danshen) has very potent inhibitory activity against ferroptosis. Mechanistically, we found that tanshinone functions as a coenzyme for NAD(P)H:quinone oxidoreductase 1 (NQO1), which detoxifies lipid peroxyl radicals and inhibits ferroptosis both in vitro and in vivo. Although NQO1 is recognized as an oxidative stress response gene, it does not appear to have a direct role in ferroptosis inhibition in the absence of tanshinone. Here, we demonstrate a gain of function of NQO1 induced by tanshinone, which is a novel mechanism for ferroptosis inhibition. Using mouse models of acute liver injury and ischemia/reperfusion heart injury, we observed that tanshinone displays protective effects in both the liver and the heart in a manner dependent on NQO1. Our results link the clinical use of tanshinone to its activity in ferroptosis inhibition.


Assuntos
Ferroptose , Salvia miltiorrhiza , Animais , Camundongos , Coenzimas/metabolismo , Mutação com Ganho de Função , Lipídeos , Espécies Reativas de Oxigênio/metabolismo , Salvia miltiorrhiza/metabolismo
2.
Medicine (Baltimore) ; 101(44): e31436, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36343087

RESUMO

BACKGROUND: Multiple studies have revealed that Traditional Chinese Medicine (TCM) prescriptions can provide protective effect on the cardiovascular system, increase the heart rate and relieve the symptoms of patients with bradyarrhythmia. In China, the TCM treatment of bradyarrhythmia is very common, which is also an effective complementary therapy. In order to further understand the application of Chinese medicines in bradyarrhythmia, we analyzed the medication rules of TCM prescriptions for bradyarrhythmia by data mining methods based on previous clinical studies. METHODS: We searched studies reporting the clinical effect of TCM on bradyarrhythmia in the PubMed and Chinese databases China National Knowledge Infrastructure database, and estimated publication bias by risk of bias tools ROB 2. Descriptive analysis, hierarchical clustering analysis and association rule analysis based on Apriori algorithm were carried out by Microsoft Excel, SPSS Modeler, SPSS Statistics and Rstidio, respectively. Association rules, co-occurrence and clustering among Chinese medicines were found. RESULTS: A total of 48 studies were included in our study. Among the total 99 kinds of Chinese medicines, 22 high-frequency herbs were included. Four new prescriptions were obtained by hierarchical cluster analysis. 81 association rules were found based on association rule analysis, and a core prescription was intuitively based on the grouping matrix of the top 15 association rules (based on confidence level), of which Guizhi, Zhigancao, Wuweizi, Chuanxiong, Danshen, Danggui, Huangqi, Maidong, Dangshen, Rougui were the most strongly correlated herbs and in the core position. CONCLUSION: In this study, data mining strategy was applied to explore the TCM prescription for the treatment of bradyarrhythmia, and high-frequency herbs and core prescription were found. The core prescription was in line with the treatment ideas of TCM for bradyarrhythmia, which could intervene the disease from different aspects and adjust the patient's Qi, blood, Yin and Yang, so as to achieve the purpose of treatment.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos sob Prescrição , Salvia miltiorrhiza , Humanos , Medicina Tradicional Chinesa , Bradicardia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Mineração de Dados , Prescrições
3.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362335

RESUMO

The SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) transcription factor play vital roles in plant growth and development. Although 15 SPL family genes have been recognized in the model medical plant Salvia miltiorrhiza Bunge, most of them have not been functionally characterized to date. Here, we performed a careful characterization of SmSPL2, which was expressed in almost all tissues of S. miltiorrhiza and had the highest transcriptional level in the calyx. Meanwhile, SmSPL2 has strong transcriptional activation activity and resides in the nucleus. We obtained overexpression lines of SmSPL2 and rSmSPL2 (miR156-resistant SmSPL2). Morphological changes in roots, including longer length, fewer adventitious roots, decreased lateral root density, and increased fresh weight, were observed in all of these transgenic lines. Two rSmSPL2-overexpressed lines were subjected to transcriptome analysis. Overexpression of rSmSPL2 changed root architectures by inhibiting biosynthesis and signal transduction of auxin, while triggering that of cytokinin. The salvianolic acid B (SalB) concentration was significantly decreased in rSmSPL2-overexpressed lines. Further analysis revealed that SmSPL2 binds directly to the promoters of Sm4CL9, SmTAT1, and SmPAL1 and inhibits their expression. In conclusion, SmSPL2 is a potential gene that efficiently manipulate both root architecture and SalB concentration in S. miltiorrhiza.


Assuntos
Benzofuranos , Salvia miltiorrhiza , Fatores de Transcrição/metabolismo , Raízes de Plantas , Salvia miltiorrhiza/metabolismo , Benzofuranos/farmacologia , Benzofuranos/metabolismo , Regulação da Expressão Gênica de Plantas
4.
Int J Mol Sci ; 23(21)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36362395

RESUMO

Tanshinones are the bioactive constituents of Danshen (Salvia miltiorrhiza Bunge), which is used in Traditional Chinese Medicine to treat cardiovascular and other diseases, and they synthesize and accumulate in the root periderm of S. miltiorrhiza. However, there is no relevant report on the initial stage of tanshinone synthesis, as well as the root structure and gene expression characteristics. The present study aims to provide new insights into how these bioactive principles begin to synthesize by characterizing possible differences in their biosynthesis and accumulation during early root development from both spatial and temporal aspects. The morphological characteristics and the content of tanshinones in roots of S. miltiorrhiza were investigated in detail by monitoring the seedlings within 65 days after germination (DAGs). The ONT transcriptome sequencing was applied to investigate gene expression patterns. The periderm of the S. miltiorrhiza storage taproot initially synthesized tanshinone on about 30 DAGs. Three critical stages of tanshinone synthesis were preliminarily determined: preparation, the initial synthesis, and the continuous rapid synthesis. The difference of taproots in the first two stages was the smallest, and the differentially expressed genes (DEGs) were mainly enriched in terpene synthesis. Most genes involved in tanshinone synthesis were up regulated during the gradual formation of the red taproot. Plant hormone signal transduction and ABC transport pathways were widely involved in S. miltiorrhiza taproot development. Five candidate genes that may participate in or regulate tanshinone synthesis were screened according to the co-expression pattern. Moreover, photosynthetic ferredoxin (FD), cytochrome P450 reductase (CPR), and CCAAT binding transcription factor (CBF) were predicted to interact with the known downstream essential enzyme genes directly. The above results provide a necessary basis for analyzing the initial synthesis and regulation mechanism of Tanshinones.


Assuntos
Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas , Abietanos , Proteínas de Plantas/metabolismo
5.
Sci Rep ; 12(1): 19633, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385104

RESUMO

Salvia miltiorrhiza Bunge (danshen in Chinese) is one of the most important medicinal cash crops in China. Previously, we showed that arbuscular mycorrhizal fungi (AMF) can promote S. miltiorrhiza growth and the accumulation of bioactive compounds. Fertilization may affect mycorrhizal efficiency, and appropriate doses of phosphate (P) and nitrogen (N) fertilizers are key factors for obtaining mycorrhizal benefits. However, the optimal fertilization amount for mycorrhizal S. miltiorrhiza remains unclear. In this study, we studied the effects of AMF on the growth and bioactive compounds of S. miltiorrhiza under different doses (low, medium, and high) of P and N fertilizer. The results showed that the mycorrhizal growth response (MGR) and mycorrhizal response of bioactive compounds (MBC) decreased gradually with increasing P addition. Application of a low (N25) dose of N fertilizer significantly increased the MGR of mycorrhizal S. miltiorrhiza, and a medium (N50) dose of N fertilizer significantly increased the MBC of phenolic acids, but decreased the MBC of tanshinones. Our results also showed that the existence of arbuscular mycorrhiza changes nutrient requirement pattern of S. miltiorrhiza. P is the limiting nutrient of non-mycorrhizal plants whereas N is the limiting nutrient of mycorrhizal plants.


Assuntos
Micorrizas , Salvia miltiorrhiza , Micorrizas/fisiologia , Nitrogênio , Fertilizantes , Necessidades Nutricionais
6.
AAPS PharmSciTech ; 23(8): 290, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316610

RESUMO

This study explores the dissolution mechanism and absorption process of compound Danshen tablets (CDTs) and compound Danshen capsules (CDCs) in vitro. Taking the cell index as the evaluation index of dissolution and absorption of multi-component solid preparations of CDTs and CDCs, it breaks through the idea of traditional research. We used real-time cell-based assay (RTCA) to provide a new idea and method for the consistency evaluation of traditional Chinese medicine (TCM) compound preparations. The drug dissolution and absorption simulation system (DDASS) was established to obtain the dissolution and absorption samples of compound Danshen solid preparations at different time points. The cell index (CI) of the sample to H9C2 cells was detected by RTCA technology, and the dissolution and absorption percentage were calculated based on this index to obtain the dissolution and absorption kinetics model. Meanwhile, one batch of tablets and one batch of capsules (batch numbers ZKC1816 and 202101001) were selected to conduct the overall animal pharmacodynamic experiment to verify the feasibility of drug effect evaluation with cell index as an indicator. The best fitting model of dissolution curves of each batch of CDTs and CDCs is the Weibull model. There was a good correlation (r > 0.86) between the dissolution-absorption-pharmacodynamic curve. Based on RTCA technology, we have established the comprehensive evaluation method for cell biology of compound Danshen solid preparations in line with the overall concept of TCM and a synchronous evaluation system of dissolution and absorption in vitro of new TCM compound solid preparations.


Assuntos
Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Animais , Cápsulas , Solubilidade , Comprimidos , Medicina Tradicional Chinesa
7.
Biomed Pharmacother ; 156: 113897, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36308918

RESUMO

Breast cancer is the most commonly diagnosed cancer in the world, and metastasis is often the main cause of death in breast cancer patients. Salvia miltiorrhiza -Ginseng (SG) herb pair is clinically used for the treatment of cardiovascular diseases and cancers. However, the pharmacological action of this pair on breast cancer is yet unclear. In this study, a spontaneous metastasis model of breast cancer was constructed to assess the therapeutic value of SG. After administration of different doses of SG, the results showed that although it did not significantly inhibit tumor growth, high-dose SG administration could inhibit tumor metastasis. Then, based on systematic pharmacology combined with Gene Expression Omnibus (GEO) database, potential targets of drugs were identified such as vascular endothelial growth factor A (VEGFA), matrix metalloproteinase (MMP9), prostaglandin endoperoxide synthase2 (PTGS2), etc. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that these targets were related to cytokine-mediated signaling pathway, cell migration and other biological processes and signaling pathways such as PI3K/Akt, etc. The systematic pharmacology analysis showed that SG effectively inhibited the VEGFA and MMP9-mediated biological events such as angiogenesis, epithelial-mesenchymal transition (EMT) and impaired tumor metastasis. Overall, our research aimed to provide new ideas for the treatment of breast cancer lung metastasis in traditional Chinese medicine.


Assuntos
Antineoplásicos , Neoplasias da Mama , Medicamentos de Ervas Chinesas , Panax , Salvia miltiorrhiza , Humanos , Feminino , Salvia miltiorrhiza/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Panax/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Antineoplásicos/farmacologia , Medicina Tradicional Chinesa , China
8.
Phytomedicine ; 107: 154477, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36215790

RESUMO

BACKGROUND: Danshen injection (DSI) is an agent extracted from the Salvia miltiorrhiza Bunge, a natural drug commonly used to alleviate kidney diseases. However, the material basis and therapeutic effects of DSI on nephrotic syndrome (NS) remain unclear. PURPOSE: To investigate the material basis of DSI and the therapeutic effects and underlying mechanisms of NS. METHODS: NS models were established using adriamycin-induced BALB/c mice and lipopolysaccharide-induced mouse podocytes (MPC-5). Following DSI and prednisone administration, kidney coefficients, 24 h urine protein, blood urea nitrogen, and serum creatinine levels were tested. Histomorphology was observed by periodic acid-Schiff staining and hematoxylin and eosin staining of the kidney sections. The glomerular basement membrane and autophagosomes of the kidneys were observed using transmission electron microscopy. Nephrin and desmin levels in the glomeruli were tested using immunohistochemistry. The viability of MPC-5 cells was tested using cell counting kit-8 after chloroquine and rapamycin administration in combination with DSI. The in vivo and in vitro protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, phosphorylated AKT (Ser473), mammalian target of rapamycin (mTOR), microtubule-associated protein light chain 3 (LC3), beclin1, cleaved caspase-3, and caspase-3 were detected using western blotting. RESULTS: Our results showed that DSI contained nine main components: caffeic acid, danshensu, lithospermic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, salvianolic acid C, salvianolic acid D, and 3, 4-Dihydroxybenzaldehyde. In in vivo studies, the NS mice showed renal function and pathological impairment. Podocytes were damaged, with decreased levels of autophagy and apoptosis, accompanied by inhibition of the PI3K/AKT/mTOR signaling. DSI administration resulted in improved renal function and pathology in NS mice, with the activation of autophagy and PI3K/AKT/mTOR signaling in the kidneys. Additionally, podocytes were less damaged and intracellular autophagosomes were markedly increased. In vitro studies have shown that DSI activated MPC-5 autophagy and reduced apoptosis via the PI3K/AKT/mTOR pathway. CONCLUSION: Collectively, this study demonstrated that DSI activated podocyte autophagy and reduced apoptosis via the PI3K/AKT/mTOR signaling, ultimately attenuating NS. Our study clarified the main components of DSI and elucidated its therapeutic effects and potential mechanisms for NS, providing new targets and agents for the clinical treatment of NS.


Assuntos
Síndrome Nefrótica , Podócitos , Salvia miltiorrhiza , Animais , Autofagia , Proteína Beclina-1/metabolismo , Caspase 3/metabolismo , Cloroquina/farmacologia , Creatinina , Desmina/metabolismo , Desmina/farmacologia , Doxorrubicina/farmacologia , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Lipopolissacarídeos/farmacologia , Mamíferos/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/metabolismo , Ácido Periódico/metabolismo , Ácido Periódico/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Podócitos/metabolismo , Prednisona/metabolismo , Prednisona/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo
9.
Sci Rep ; 12(1): 18212, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307498

RESUMO

Flavonoid secondary metabolites can treat and prevent many diseases, but systematic studies on regulation of the biosynthesis of such metabolites in aboveground parts of Salvia miltiorrhiza are lacking. In this study, metabonomic and transcriptomic analyses of different S. miltiorrhiza phenotypes were conducted to explore pathways of synthesis, catalysis, accumulation, and transport of the main flavonoid secondary metabolites regulating pigment accumulation. Tissue localization and quantitative analysis of flavonoid secondary metabolites were conducted by laser scanning confocal microscopy (LSCM). A total 3090 differentially expressed genes were obtained from 114,431 full-length unigenes in purple and green phenotypes, and 108 functional genes were involved in flavonoid biosynthesis. Five key phenylpropane structural genes (PAL, 4CL, ANS, 3AT, HCT) were highly differentially expressed, and four transcription factor genes (MYB, WRKY, bHLH, bZiP) were identified. In addition, six GST genes, nine ABC transporters, 22 MATE genes, and three SNARE genes were detected with key roles in flavonoid transport. According to LSCM, flavonoids were mainly distributed in epidermis, cortex, and collenchyma. Thus, comprehensive and systematic analyses were used to determine biosynthesis, accumulation, and transport of flavonoids in stems and leaves of different S. miltiorrhiza phenotypes. The findings will provide a reference for flavonoid production and cultivar selection.


Assuntos
Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transcriptoma , Folhas de Planta/genética , Folhas de Planta/metabolismo
10.
Medicine (Baltimore) ; 101(37): e30698, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36123860

RESUMO

BACKGROUND: Heart failure (HF) is considered the clinical endpoint of all cardiovascular diseases (CVDs). Although a large number of HF drugs and therapies have been developed, it is still need to find therapies with better clinical efficacy and fewer side effects. The purpose of this systematic evaluation is to assess the efficacy and safety of Danshen decoction on HF and the improvement of cardiac function (CF). METHODS: Four databases will be searched to identify any eligible studies, and this protocol does not require ethics committee review as the research is based on published articles. There are no restrictions set for the language, publication date, or status of the study. The clinical effective rate (CER) of HF treatment is considered to be the main result. CF, various serum inflammatory factors, and adverse events were defined as secondary outcomes. When more than 1 article is used to study the changes and results of the same index, we will conduct a meta-analysis. If the heterogeneity is not statistically significant (P > .10 or I2 < 50%), a fixed-effect model will be established to estimate the overall intervention effect. Otherwise, random effect models will be used to provide more conservative results. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will provide reliable evidence-based basis for the clinical application of Danshen decoction in the treatment of HF.


Assuntos
Insuficiência Cardíaca , Salvia miltiorrhiza , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
11.
BMC Microbiol ; 22(1): 231, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180825

RESUMO

BACKGROUND: S. miltiorrhiza root rot is a soil-borne disease mainly caused by Fusarium solani and Fusarium oxysporum, which has spread rapidly in China in recent years. To reduce the amount of pesticides to control this plant fungal disease, biological control using endophytic bacteria is a promising method. Many endophytic bacteria show good biocontrol potential against various plant fungal diseases. The aims of this study were to isolate and identify endophytic bacteria with antifungal activity from Salvia miltiorrhiza plant tissue. In order to increase antifungal substances production, the culture conditions of the isolated DS-R5 strain were optimized through response surface methodology. RESULTS: Thirteen endophytic bacteria with antifungal activity against the target pathogenic fungus were successfully screened. The DS-R5 strain that had the strongest antifungal activity was identified based on morphological, physiological and biochemical characteristics, 16S rRNA and gyrB sequence analysis.The results of response surface methodology experiments showed that the optimal values of the three significant factors were as follows: medium volume, 51.0 ml; initial pH, 6.7; fermentation temperature, 33.1 °C. Under these optimal culture conditions, the titer of antifungal substances produced by the DS-R5 strain was 77.6% higher than that under the initial culture conditions. CONCLUSIONS: The antifungal activity of endophytic bacteria from Salvia miltiorrhiza has been demonstrated for the first time, which may benefit future crop quality and production. In addition, response surface methodology can be well applied the optimization of culture conditions for antifungal substance, which lays the foundation for further research on strain DS-R5.


Assuntos
Fusarium , Micoses , Praguicidas , Salvia miltiorrhiza , Antifúngicos/farmacologia , Bactérias/genética , Fusarium/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , RNA Ribossômico 16S/genética , Salvia miltiorrhiza/genética , Solo
12.
Zhongguo Zhong Yao Za Zhi ; 47(18): 4886-4894, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36164898

RESUMO

14-3-3 proteins are important proteins in plants, as they regulate plant growth and development and the response to biotic or abiotic stresses. In this study, a 14-3-3 gene(GenBank accession: OM683281) was screened from the cDNA library of the medicinal species Salvia miltiorrhiza by yeast two-hybrid and cloned. The open reading frame(ORF) was 780 bp, encoding 259 amino a cids. Bioinformatics analysis predicted that the protein was a non-transmembrane protein with the molecular formula of C_(1287)H_(2046)N_(346)O_(422)S_9, relative molecular weight of 29.4 kDa, and no signal peptide. Homologous sequence alignment and phylogenetic tree analysis proved that the protein belonged to 14-3-3 family and had close genetic relationship with the 14-3-3 proteins from Arabidopsis thaliana, Oryza sativa, and Nicotiana tabacum. The 14-3-3 gene was ligated to the prokaryotic expression vector pGEX-4 T-1 and then transformed into Escherichia coli BL21 for the expression of recombinant protein. Real-time fluorescent quantitative PCR showed that the expression of this gene was different among roots, stems, leaves, and flowers of S. miltiorrhiza. To be specific, the highest expression was found in leaves, followed by stems, and the lowest expression was detected in flowers. S. miltiorrhiza plants were treated with 15% PEG(simulation of drought), and hormones salicylic acid, methyl jasmonate, and ethephon, respectively, and the expression of 14-3-3 gene peaked at the early stage of induction. Therefore, the gene can quickly respond to abiotic stresses such as drought and plant hormone treatments such as salicylic acid, jasmonic acid, and ethylene. This study lays the foundation for revealing the molecular mechanism of 14-3-3 protein regulating tanshinone biosynthesis and responding to biotic and abiotic stresses.


Assuntos
Salvia miltiorrhiza , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Hormônios/metabolismo , Filogenia , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas Recombinantes/genética , Ácido Salicílico/metabolismo , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo
13.
Biomed Res Int ; 2022: 3816258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147634

RESUMO

Radix Salvia miltiorrhiza (RSM) is widely used for the clinical improvement of inflammatory diseases. However, the actions of RSM in the treatment of ankylosing spondylitis (AS) have not been fully explored. Therefore, this study was designed to use retrospective clinical data mining approach to understand the effects of RSM on AS-related immuno-inflammatory processes, use network pharmacology to predict therapeutic targets of RSM, and to further investigate the pharmacological molecular mechanism in vitro. RSM treatment has a long-term correlation with the improvement of AS-related immuno-inflammatory indicators through computational models. We established protein-protein interaction networks, conducted KEGG analysis to enrich significant TNF pathways, and finally obtained three core targets of RSM in the treatment of AS, namely, prostaglandin endoperoxide synthase 2 (PTGS2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Screening of RSM active ingredients with node degree greater than 20 yielded cryptotanshinone and tanshinone IIA, and previous studies have reported their anti-inflammatory effects. In vitro, both cryptotanshinone and tanshinone IIA significantly inhibited the expressions of PTGS2, IL-6, and TNF-α in peripheral blood mononuclear cells in AS patients. In conclusion, cryptotanshinone and tanshinone IIA, which are the active components of RSM, may inhibit the activation of TNF signaling pathway in AS patients by downregulating the expression of PTGS2, IL-6, and TNF-α. These findings illustrate that RSM may be a promising therapeutic candidate for AS, but further validation is required.


Assuntos
Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Espondilite Anquilosante , Abietanos , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2 , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Interleucina-6 , Leucócitos Mononucleares/metabolismo , Farmacologia em Rede , Fenantrenos , Estudos Retrospectivos , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo
14.
Plant Sci ; 325: 111462, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36126879

RESUMO

Laccase (LAC) is a blue multicopper oxidase that contains four copper ions, which is involved in lignin polymerization and flavonoid biosynthesis in plants. Although dozens of LAC genes have been identified in Salvia miltiorrhiza Bunge (a model medicinal plant), most have not been functionally characterized. Here, we explored the expression patterns and the functionality of SmLAC25 in S. miltiorrhiza. SmLAC25 has a higher expression level in roots and responds to methyl jasmonate, auxin, abscisic acid, and gibberellin stimuli. The SmLAC25 protein is localized in the cytoplasm and chloroplasts. Recombinant SmLAC25 protein could oxidize coniferyl alcohol and sinapyl alcohol, two monomers of G-lignin and S-lignin. To investigate its function, we generated SmLAC25-overexpressed S. miltiorrhiza plantlets and hairy roots. The lignin content increased significantly in all SmLAC25-overexpressed plantlets and hairy roots, compared with the controls. However, the concentrations of rosmarinic acid and salvianolic acid B decreased significantly in all the SmLAC25-overexpressed lines. Further studies revealed that the transcription levels of some key enzyme genes in the lignin synthesis pathway (e.g., SmCCR and SmCOMT) were significantly improved in the SmLAC25-overexpressed lines, while the expression levels of multiple enzyme genes in the salvianolic acid biosynthesis pathway were inhibited. We speculated that the overexpression of SmLAC25 promoted the metabolic flux of lignin synthesis, which resulted in a decreased metabolic flux to the salvianolic acid biosynthesis pathway.


Assuntos
Salvia miltiorrhiza , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Lignina/metabolismo , Alcenos/metabolismo , Polifenóis/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
15.
Biomed Res Int ; 2022: 3002353, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119929

RESUMO

lncRNAs and mRNA are closely associated with hypertensive renal damage, and Astragalus membranaceus and Salvia miltiorrhiza (AS) have a therapeutic effect; however, the mechanism of AS to ameliorate hypertensive renal damage through the co-expression network of lncRNA-mRNA was unclear. In this study, we investigated the role of AS regulated the coexpression network of lncRNA-mRNA in improving hypertensive renal damage. Sixteen 24-week old spontaneous hypertensive rats (SHRs) were randomly divided into model group (M) and drug intervention group (AS, 5.9 g/kg), 8 Wistar Kyoto rats (WKY) of the same age as normal group (N). The treatment of rats was 4 weeks. Detecting the change of blood pressure, renal pathology and renal function related indicators, and lncRNA and mRNA sequencing and joint analysis was performed on the kidney. AS reduced blood pressure; decreased urine NAG, urine mALB, serum CysC, and IL-6; and improved renal pathology compared with group M. Simultaneously, AS reversed the disordered expression of 178 differential expression (DE) mRNAs and 237 DE-lncRNAs in SHRs, and their joint analysis showed that 13 DE-mRNAs and 32 DE-lncRNAs were coexpressed. Further analysis of 13 coexpressed DE-mRNAs showed negative regulation of blood pressure and fatty acid beta-oxidation was highly enriched in GO pathways, PPAR signaling pathway was highly enriched in KEGG pathways, and the verification related to these pathways was also highly consistent with the sequence. AS can alleviate hypertensive renal damage through the coexpression network of lncRNA-mRNA, of which coexpressed 13 DE-mRNAs and 32 DE-lncRNAs were the important targets, and the pathway negative regulation of blood pressure, fatty acid beta-oxidation, and PPAR signaling pathway play a major regulatory role.


Assuntos
Hipertensão , RNA Longo não Codificante , Salvia miltiorrhiza , Animais , Astragalus propinquus , Ácidos Graxos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Interleucina-6 , Rim/metabolismo , Receptores Ativados por Proliferador de Peroxissomo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR
16.
Mol Med Rep ; 26(5)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36069225

RESUMO

Tanshinone IIA (Tan 2A) is a lipid­soluble compound extracted from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It protects neuron and microvascular endothelial cells against hypoxia/ischemia both in vitro and in vivo however the mechanism is not fully known. Glucose transporter 1 (GLUT­1) is ubiquitously expressed in all types of tissue in the human body and serves important physiological functions due to its glucose uptake ability. The present study evaluated the role of Tan 2A in regulating GLUT­1 expression and its potential mechanism. RT­PCR and western Blot were used to detect the expression of GLUT­1. Si RNA mediated knockdown and CHIP assay were used to explore the mechanism of Tan 2A on GLUT­1expression. Tan 2A treatment induced expression of GLUT­1 and subsequently increased glucose uptake in endothelial cells (ECs). Furthermore, mRNA expression levels of vascular endothelial cell growth factor, BCL2 interacting protein 3 and enolase 2, which are target genes for hypoxia­inducible factor­1α (HIF­1α), were significantly upregulated by Tan 2A. Co­immunoprecipitation demonstrated that Tan 2A markedly increased the association of HIF­1α with recombination signal­binding protein for immunoglobulin κJ region (RBPJκ). Moreover, knockdown of HIF­1α and RBPJκ significantly reversed the regulatory effect of Tan 2A on mRNA expression levels of these genes in ECs. The results of the present study suggested that HIF­1α partially mediated the regulatory effect of Tan 2A on GLUT­1 expression in ECs. Therefore, GLUT­1 may be a potential therapeutic target for Tan 2A.


Assuntos
Células Endoteliais , Salvia miltiorrhiza , Abietanos , Células Endoteliais/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Humanos , RNA Mensageiro/metabolismo , Salvia miltiorrhiza/química , Transdução de Sinais , Triacetonamina-N-Oxil/metabolismo , Triacetonamina-N-Oxil/farmacologia
17.
Int J Mol Sci ; 23(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36142520

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, thus treatments for it have attracted lots of interest. In this study, the Salviae miltiorrhizae Radix et Rhizoma (SMRR) polysaccharide was isolated by hot water extraction and ethanol precipitation, and then purified by DEAE anion exchange chromatography and gel filtration. With a high-fat-diet-induced obesity/NAFLD mouse model, we found that consumption of the SMRR polysaccharide could remarkably reverse obesity and its related progress of NAFLD, including attenuated hepatocellular steatosis, hepatic fibrosis and inflammation. In addition, we also reveal the potential mechanism behind these is that the SMRR polysaccharide could regulate the gut-liver axis by modulating the homeostasis of gut microbiota and thereby improving intestinal function.


Assuntos
Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Salvia miltiorrhiza , Animais , Carboidratos da Dieta , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Etanol , Fígado , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Salvia miltiorrhiza/química , Água
18.
Int J Mol Sci ; 23(16)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36012649

RESUMO

Jasmonic acid (JA) is a vital plant hormone that performs a variety of critical functions for plants. Salvia miltiorrhiza Bunge (S. miltiorrhiza), also known as Danshen, is a renowned traditional Chinese medicinal herb. However, no thorough and systematic analysis of JA biosynthesis genes in S. miltiorrhiza exists. Through genome-wide prediction and molecular cloning, 23 candidate genes related to JA biosynthesis were identified in S. miltiorrhiza. These genes belong to four families that encode lipoxygenase (LOX), allene oxide synthase (AOS), allene oxide cyclase (AOC), and 12-OPDA reductase3 (OPR3). It was discovered that the candidate genes for JA synthesis of S. miltiorrhiza were distinct and conserved, in contrast to related genes in other plants, by evaluating their genetic structures, protein characteristics, and phylogenetic trees. These genes displayed tissue-specific expression patterns concerning to methyl jasmonate (MeJA) and wound tests. Overall, the results of this study provide valuable information for elucidating the JA biosynthesis pathway in S. miltiorrhiza by comprehensive and methodical examination.


Assuntos
Ciclopentanos , Oxilipinas , Salvia miltiorrhiza , Clonagem Molecular , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Oxilipinas/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo
19.
Phytomedicine ; 105: 154386, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35985183

RESUMO

BACKGROUND: Severe inflammation of the lungs results from acute lung injury (ALI), a common life-threatening lung disease with a high mortality rate. The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays essential roles in diverse biological processes including inflammation, metabolism, development, and immune response. Salvianolactone acid A (SA) is a terpenoid derived from the herb Salvia miltiorrhiza. However, there is a scarcity of experimental evidence indicating whether the effect of SA on ALI occurs via PPAR-γ. METHODS: SA (20 or 40 mg/kg, i.g., 1 time/day) was administered to mice for 3 d, followed by the induction of ALI by intranasal lipopolysaccharide (LPS, 10 mg/kg). The lung function and levels of inflammation, reactive oxygen species (ROS), immune cells, apoptosis, and PPAR-γ were examined. The antagonistic activity of GW9662 (GW, 1 µM, specific PPAR-γ blocker) and PPAR-γ transfection silencing against SA (10 µM) in BEAS-2B cells induced by LPS (10 µg/ml, 24 h) was also investigated to assess whether the observed effects caused by SA were mediated by PPAR-γ. RESULTS: The results showed that lung histopathological injury, the B-line, the fluorescence intensity of live small animal, and the biomarkers in BALF or lung in the treatment of SA could regulate significantly. In addition, SA obviously decreased the levels of ROS and apoptosis in the primary lung cells, and MDA, increased the levels of GSH-Px and SOD. SA reduced levels of macrophages and neutrophils. Furthermore, SA reduced the protein levels of Keap-1, Cleaved-caspase-3, Cleaved-caspase-9, p-p65/p65, NLRP3, IL-1ß, and upregulated the levels of p-Nrf2/Nrf2, HO-1, Bcl-2/Bax, PPAR-γ, p-AMPK/AMPK in lung tissue. In addition, silencing and inhibition of PPAR-γ effectively decreased the protective effects of SA in BEAS-2B cells induced by LPS, which might indicate that the active molecules of SA regulate ALI via mediation by PPAR-γ, which exhibited that the effect of SA related to PPAR-γ. CONCLUSIONS: The anti-ALI effects of SA were partially mediated through PPAR-γ signaling. These data provide the molecular justification for the usage of SA in treating ALI and can assist in increasing the comprehensive utilization rate of Salvia miltiorrhiza.


Assuntos
Lesão Pulmonar Aguda , Salvia miltiorrhiza , Proteínas Quinases Ativadas por AMP , Animais , Inflamação , Lipopolissacarídeos , Pulmão , Camundongos , Fator 2 Relacionado a NF-E2 , NF-kappa B , PPAR gama , Espécies Reativas de Oxigênio
20.
Comput Math Methods Med ; 2022: 1481294, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35983530

RESUMO

Aims: To investigate the effect of injectable salvia polyphenolic acid on the improvement of limb movement and cognitive dysfunction in acute stroke patients. Materials and Methods: The clinical data of 90 acute stroke patients were collected for retrospective study and divided into 45 cases each in the comparison group and the observation group according to the different treatment methods; using basic treatment + salvianolic acid, the comparison group implemented conventional alteplase and butalbital treatment, and the observation group used injectable salvianolic acid treatment, to observe and compare the clinical efficacy, changes in neurological deficits, cognitive function, and motor function scores before and after treatment in the two groups. Results: The NIHSS (National Institute of Health stroke scale) score, cerebral infarct volume, NSE (neuron-specific enolase), and S100ß (A neurotrophic factor) levels were reduced after treatment compared with those before treatment in this group, and the NIHSS score, cerebral infarct volume, NSE, and S100ß levels in the observation group were lower than those in the comparison group after treatment, and the difference was statistically significant (P < 0.05). Compared with the clinical efficacy of the comparison group and the observation group, the treatment effect of the observation group was better than that of the comparison group, and the difference was statistically significant (P < 0.05). After treatment, the cognitive function and motor function scores of both groups were significantly improved compared with those before treatment, and the degree of improvement of each score in the observation group was significantly better than that in the comparison group (P < 0.05). During the trial, two patients in the comparison group developed a generalized rash and withdrew from the experiment, and the rash subsided after anti-allergic treatment, and no significant adverse events were observed in the remaining participants. There was no statistically significant difference in liver and kidney function and cardiac enzyme test indexes between the two groups of patients at 14 days of treatment (P > 0.05). Conclusion: Danshen polyphenolic acid for injection has definite clinical efficacy in the treatment of acute ischemic stroke, and it can effectively improve cognitive and motor functions and promote neurological recovery in patients with high safety.


Assuntos
Disfunção Cognitiva , Exantema , AVC Isquêmico , Salvia miltiorrhiza , Acidente Vascular Cerebral , Infarto Cerebral , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
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