PHYTOMEDICINE
·
2020
·
IF 4.268
Jian Sheng,Qingfen Meng,Zhenzhong Yang,Jianli Guan,Yu Zhao,Jide Zhang,Yingchao Wang,Lu Zhao,Yi Wang
Background Thromboembolic events are leading causes of mortality and morbidity all over the world. Tongmai (TM) is a botanical drug with valid clinical efficacy and safety in the management of thrombosis and ischemic cardiovascular diseases, however, its active compounds and underlying mechanism are largely unclear. Purpose To investigate the endogenous effects, therapeutic mechanism and active compounds of TM in thrombus formation. Study design Combined with transgenic zebrafish models and high-content imaging system, this study evaluated the endogenous antithrombotic effects of TM and screened for the active compounds. Methods The PHZ-induced thrombotic model in erythrocytes or platelets labeled transgenic zebrafish were established, to dynamically evaluate the antithrombotic effects of TM. The oxidative damage levels were analyzed by specific fluorescent probes, and the expression levels of key factors in coagulation cascades and platelet activation were examined by QPCR. TM were dissected into fractions by reverse phase chromatography and subsequently screened for their antithrombotic effects in the transgenic fish models. The compounds of the active TM fraction were then analyzed by UPLC-Q-TOF analysis and further verified for their antithrombotic effects and mechanisms. Results In PHZ-induced zebrafish thrombotic model, TM incubation markedly increased cardiac blood flow, decreased peripheral erythrocytes aggregation, and recovered peripheral platelet circulation. Besides, the levels of oxidative stress and lipid peroxidation were increased in the PHZ-induced thrombotic fish, which were greatly decreased by TM treatment. Moreover, TM significantly reduced the expression of coagulation factor II (thrombin) and the downstream fibrinogen. In order to identify the active compounds of TM, four fractions were separated from the extract by reverse phase chromatography, which were subsequently screened for their antithrombotic effects in the fish model. As a result, fraction 4 showed the strongest effect in inhibiting thrombosis. Finally, through UPLC-Q-TOF analysis and endogenous screening, cryptotanshione was identified as the main active compound with antithrombotic effects. Conclusion Our study demonstrated the endogenous antithrombotic effects of TM, which is possibly mediated by inhibiting oxidative stress and coagulation cascade. Cryptotanshione was identified as a major compound with antithrombotic activity and is a promising candidate for novel antithrombotic therapy.
研究领域:
药理学
·
心血管疾病
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Luting Wang,Lin Xu,Junfeng Du,Xiao Zhao,Mei Liu,Jianfang Feng,Kaili Hu
Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood–brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved with the ability to enhance other drugs’ transport across the BBB. The Bo-TSA-NP, with a particle size of about 160 nm, drug loading of 3.6%, showed sustained release and P-glycoprotein (P-gp) inhibition property. It demonstrated a significantly higher uptake by 16HBE cells in vitro through the clathrin/caveolae-mediated endocytosis and micropinocytosis. Following intranasal (IN) administration, Bo-TSA-NP significantly improved the preventive effect on a rat model of CIRI with improved neurological scores, decreased cerebral infarction areas and a reduced content of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) in rat brain. In conclusion, these results indicate that Bo-TSA-NP is a promising nose-to-brain delivery system that can enhance the prevention effect of TSA on CIRI.
研究领域:
药剂学
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神经科学
·
药物递送系统
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DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Ruoxin Tu,Yining Wang,Ru Xu,Shusheng Wang,Jiabin Cai,Lin Sun,Pengfei Gao
Despite therapeutic advances, hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While dihydrotanshinone I (DHT) shows promising anticancer potential, its molecular mechanisms in HCC remain unexplored. Here, we unveil a novel chemokine (C-C Motif) receptor 5(CCR5)-mediated regulatory network targeted by DHT in HCC treatment. This study identifies CCR5 as a crucial survival factor in HCC, uncovers a novel CCR5-Nuclear factor erythroid 2-related factor 2(NRF2) regulatory axis, and reveals a dual-targeting mechanism of DHT through direct CCR5 inhibition and Reactive oxygen species(ROS)-dependent cell death induction, validating its therapeutic efficacy by disrupting redox homeostasis. This study uncovers a novel CCR5-ROS-NRF2 signaling axis in HCC and establishes DHT as a promising therapeutic agent through its unique targeting mechanism. These findings provide new insights into HCC pathogenesis and present an innovative therapeutic strategy for HCC treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL BOTANY
·
2020
·Vol. 71
·期 19
·5948-5962
·
IF 5.908
Deng Changping,Shi Min,Fu Rong,Zhang Yi,Wang Qiang,Zhou Yang,Wang Yao,Ma Xingyuan,Kai Guoyin
Phenolic acids and tanshinones are major bioactive ingredients in Salvia miltiorrhiza, which possess pharmacological activities with great market demand. However, transcriptional regulation of phenolic acid and tanshinone biosynthesis remains poorly understood. Here, a basic leucine zipper transcription factor (TF) named SmbZIP1 was screened from the abscisic acid (ABA)-induced transcriptome library. Overexpression of SmbZIP1 positively promoted phenolic acid biosynthesis by enhancing expression of biosynthetic genes such as cinnamate-4-hydroxylase (C4H1). Furthermore, biochemical experiments revealed that SmbZIP1 bound the G-Box-like1 element in the promoter of the C4H1 gene. Meanwhile, SmbZIP1 inhibited accumulation of tanshinones mainly by suppressing the expression of biosynthetic genes including geranylgeranyl diphosphate synthase (GGPPS) which was confirmed as a target gene by in vitro and in vivo experiments. In contrast, the phenolic acid content was reduced and tanshinone was enhanced in CRISPR/Cas9 [clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9]-mediated knockout lines. In addition, the previously reported positive regulator of tanshinone biosynthesis, SmERF1L1, was found to be inhibited in SmbZIP1 overexpression lines indicated by RNA sequencing, and was proven to be the target of SmbZIP1. In summary, this work uncovers a novel regulator and deepens our understanding of the transcriptional and regulatory mechanisms of phenolic acid and tanshinone biosynthesis, and also sheds new light on metabolic engineering in S. miltiorrhiza.
研究领域:
植物生物学
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分子生物学
·
药理学
·
基因工程
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产品关联
DOI
PubMed
高影响因子
GLYCOCONJUGATE JOURNAL
·
2016
·Vol. 34
·期 1
·3-12
·
IF 1.828
Wang Dongdong,DanXu,Sun Yuelin,Wu Yuanyuan,Ma Lili,Duan Jinyou
In this study, we synthesized a novel water-soluble low molecular chitosan (LMC) derivative through Vilsmeier reaction and reductive amination reaction. The derivative was characterized by UV-visible spectroscopy, 1 H NMR, FTIR and SEM techniques. The results showed that the derivative effectively reduced the cell viability rate, inhibited cell metastasis, induced cell apoptosis and dissipated mitochondrial membrane potential (ΔΨm). Moreover, the antitumor activity was strengthened with the increase of the degree of substitution of tanshinone I (TanI). These findings provided important support for developing new water-soluble antitumor agent and expand the scope of application of LMC.
研究领域:
药物化学
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肿瘤学
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生物材料学
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DOI
PubMed
高影响因子
JOURNAL OF SOLUTION CHEMISTRY
·
2018
·Vol. 47
·期 12
·2068-2081
·
IF 1.401
Zhang Hua-xin,Liu E.,Zhou Dan,Xia Qing-hua
Crytotanshinone (CTSO) is a Chinese herbal medicine active ingredient isolated from Salvia miltiorrhiza. In this work, the interaction of CTSO and human serum albumin (HSA) was studied by fluorescence spectra, ultraviolet spectra, circular dichroism (CD) spectra, molecular probe and molecular modeling methods. The results showed that the endogenous fluorescence of HSA was quenched by CTSO through a static mechanism. The number of binding sites, equilibrium constants, and thermodynamic parameters of the reaction were calculated at three different temperatures. The positive enthalpy change (Δ H θ ) and entropy change (Δ S θ ) revealed that the interaction was an endothermic as well as an entropy-driven process, where hydrophobic power played the major role in stabilizing the structure of the new complex. Site-selective binding experiments were carried out using warfarin and ibuprofen as probes, which proved that CTSO binds to Sudlow’s site II in subdomain IIIA of the HSA molecule. Circular dichroism (CD) spectra was employed to detect the α -helix and β -strand contents in HSA before and after the binding of CTSO. Based on the experimental results, the structure of the CTSO–HSA complex was calculated by docking CTSO to the proven site using molecular modeling. The study obtained comprehensive information on structure and thermodynamics, which is essential for understanding the bioaffinity, delivery process and pharmacological mechanism.
研究领域:
药理学
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生物化学
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产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Tengfei Li,Duo Li,Xinyu Xu,Yantong Zhu,Margaret Phiri,Shunli Ji,Chang Shu,Li Ding
In this study, the hydrophobic drug Tanshinone ⅡA (Tan ⅡA) as a therapeutic drug was loaded into naphthalene acetic acid-phenylalanine-phenylalanine-glycine hydrogel (Nap-FFG) to construct the supramolecular hydrogels. Nap-FFG hydrogel fibers crosslinked into a network-like structure by self-assembly of polypeptides and then achieved drug loading. The rheological assay of Tan ⅡA-loaded Nap-FFG hydrogel (Tan@Nap-FFG) had excellent shear resistance, allowing it to maintain gel state. Anticoagulant and anti-oxidant assay showed Tan@Nap-FFG hydrogels synergistically resisted hydrogen peroxide damage and inhibited platelet aggregation caused by ADP, which was suitable for the therapy of cardiovascular diseases. In-vitro release assays and in-vivo pharmacokinetic had demonstrated that hydrogels released drugs slowly, reduced drug toxicity , and improved pharmacokinetic behavior. In summary, Tan@Nap-FFG hydrogels was expected to be developed as a novel injection for cardiovascular therapy.
研究领域:
药学
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生物材料
·
医学
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产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Chao Luo,Weibin Wu,Shuaijie Lou,Saiqi Zhao,Kai Yang
Tanshinone IIA (TA) is a major active ingredient of traditional Chinese medicine Salvia miltiorrhiza Bunge (Danshen) with poor solubility. The strong crystallinity of TA is the main reason for its poor solubility. Since sodium alginate (SA) can suppress the drug crystal growth and has excellent biocompatibility , we hypothesize that SA may be an ideal matrix for preparing solid dispersion (SD) to improve the dissolution rate and bioavailability of TA. In this study, a novel TA-SA-SD was developed via a rapid one-pot approach for improving the dissolution rate, in vivo bioavailability, and pharmacological activity of TA. The results of scanning electron microscopy (SEM), X-ray diffraction (XRD) confirmed the SD process will reduce the crystallinity of TA. The crystallinity reduction of TA in TA-SA-SD can obviously improve the dissolution rate, oral absorption rate and in vivo bioavailability, the relative bioavailability of TA-SA-SD (1:6) and TA-SA-SD (1:8) were 2.08 and 2.75 folds of TA, respectively. In vitro anti-inflammatory assays were performed in RAW264.7 cells by ELISA , fluorescence microscope and Western blot analysis . The results revealed that the TA-SA-SD can significantly improve the pharmacological activity of TA. This study provides a successful method of incorporating hydrophobic drugs into hydrophilic bio-macromolecules matrices for improving the dissolution rate and bioavailability.
研究领域:
药剂学
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药理学
·
中医药学
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Tingjun Dong,Ning Yang,Jian Qin,Chengcheng Zhao,Tingyu Gao,Hao Ma,Caili Zhu,Huan Xu
Renal fibrosis plays a key role in the pathogenesis of chronic kidney disease (CKD), in which the persistent high expression of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) contributes to the progression of CKD to renal failure. In order to improve the solubility, bioavailability, and targeting of tanshinone IIA (Tan IIA), a novel targeting material, aminoethyl anisamide-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphate ethanolamine (AEAA-PEG-DSPE, APD) modified Tan IIA liposomes (APD-Tan IIA-L) was constructed. An animal model of glomerulonephritis induced by doxorubicin in BALB/c mice was established. APD-Tan IIA-L significantly decreased blood urea nitrogen and serum creatinine (SCr), and the consequences of renal tissue oxidative stress indicators showed that APD-Tan IIA-L downregulated malondialdehyde, upregulated superoxide dismutase, catalase, and glutathione peroxidase. Masson’s trichrome staining showed that the deposition of collagen in the APD-Tan IIA-L group decreased significantly. The pro-fibrotic factors (fibronectin, collagen I, TGF-β1, and α-SMA) and epithelial–mesenchymal transition marker (N-cadherin) were significantly inhibited by APD-Tan IIA-L. By improving the microenvironment of fibrotic kidneys, APD-Tan IIA-L attenuated TGF-β1-induced excessive proliferation of fibroblasts and alleviated oxidative stress damage to the kidney, providing a new strategy for the clinical treatment of renal fibrosis.
研究领域:
药理学
·
肾脏病学
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产品关联
DOI
PubMed
高影响因子
Analytical Cellular Pathology
·
2022
·
IF 4.133
Yingru Zhang,Yiyang Zhao,Jingwen Liu,Chunpu Li,Ying Feng,Shasha Jiang,Xiaoting Sun,Xueqing Hu,Yan Wang
Tanshinone IIA (TanIIA) is the main active ingredient in the fat-soluble components isolated from Salvia miltiorrhiza Bunge. Our previous studies have convincingly proved that TanIIA is an effective drug against human colorectal carcinoma cells. In order to further demonstrate the effect of TanIIA on CRC, we carried out exploratory research about it in vivo and in vitro. The results demonstrated that TanIIA were observably more effective than control group in preventing tumor growth, and it has increased the survival time. Cancer cells viability and proliferation were accompanied by concentration and time dependent decline reached with TanIIA. We found that TanIIA altered the morphology of cytoskeleton and it could obviously induce apoptosis of colorectal cancer cells and block the cells in the G0/G1 phase. TanIIA also increased phosphorylation of p38MAPK, upregulated ATF-2 expression and downregulated Transgelin-2 expression, which could be reversed by SB203580, a p38MAPK-specific inhibitor. Our results suggested that TanIIA could induce apoptosis of colorectal cancer and block the cells in G0/G1 phase involved in downregulating the expression of Transgelin-2 through p38MAPK signal pathway.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Yifeng Fan,Shengyu Kang,Tong Shao,Linhao Xu,Jian Chen
Although doxorubicin (DOX) is a common chemotherapeutic drug, the serious nephrotoxicity caused by DOX-induced renal fibrosis remains a considerable clinical problem. Tanshinone IIA (Tan IIA), a compound extracted from Salvia miltiorrhiza , has been reported to have an anti-fibrotic effect. Therefore, this study investigated the molecular pathway whereby Tan IIA protects the kidneys from DOX administration. DOX (3 mg/kg body weight) was intraperitoneally administered every 3 d for a total of 7 injections (cumulative dose of 21 mg/kg) to induce nephrotoxicity. Then, Tan IIA (5 or 10 mg/kg/d) was administered by intraperitoneal injection for 28 d. In an in vitro study, 293 T cells were cultured and treated with DOX and Tan IIA for 24 h. Tan IIA reduced the blood urea nitrogen levels elevated by DOX while increasing superoxide dismutase activity, down-regulating reactive oxygen species, ameliorating renal-tubule thickening, and rescuing mitochondrial morphology. Additionally, Tan IIA reduced the renal collagen deposition, increased ATP production and complex-I activity, down-regulated transforming growth factor-β1 (TGF-β1) and thrombospondin-1 (TSP-1), and up-regulated sirtuin 3 (SIRT3). Tan IIA significantly increased cell viability. Additionally, RNA interference was employed to silence the expression of SIRT3, which eliminated the effect of Tan IIA in suppressing the expression of TGF-β1 and TSP-1. In conclusion, Tan IIA ameliorated DOX-induced nephrotoxicity by attenuating oxidative injury and fibrosis. The Tan IIA-induced rescue of mitochondrial morphology and function while alleviating renal fibrosis may be associated with the activation of SIRT3 to suppress the TGF-β/TSP-1 pathway.
研究领域:
药理学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shaoping Ma,Changyong Cai,Xuhong Guo,Zhijian Tan
Membranes have been used as versatile tools for the separation of various natural products; however, the selective separation of structural analogs of natural products using membranes remains challenging. In this study, biocomposite membranes based on poly(ionic liquids) and different natural fibers (jute, cotton, or wool) were successfully prepared. Natural fibers can regulate the microstructure and improve the mechanical properties of membranes. Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, atomic force microscopy, Brunauer-Emmett-Teller analysis, and thermo gravimetric analysis were used to characterize the membranes. The membranes were used to separate tanshinone homologs (tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone I), allowing cryptotanshinone to penetrate the membrane while rejecting tanshinone I. A maximal selectivity of 44.57 % was obtained for the tanshinone homologs using a one-step separation protocol. These poly(ionic liquids)/natural fiber membranes possess high water flux, good self-cleaning, and good antibacterial properties. The membranes were effective in separating tanshinone homologs and have the potential to separate other natural homologs.
研究领域:
材料科学
·
天然产物化学
·
分离技术
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）