PHARMACEUTICAL BIOLOGY
·
2017
·
IF 1.916
Xu-Xin Zhang,Yun-Feng Cao,Li-Xuan Wang,Xiao-Lin Yuan,Zhong-Ze Fang
Contents: Danshen is a popular herb employed to treat cardiovascular and cerebrovascular diseases worldwide. Danshen–drug interaction has not been well studied.Objective: The inhibitory effects of four major tanshinones (tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone I) on UDP-glucuronosyltransferases (UGTs) isoforms were determined to better understand the mechanism of danshen–prescription drugs interaction.Materials and methods: In vitro recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed. Tanshinones (100 μM) was used to perform the initial screening of inhibition capability. High-performance liquid chromatography (HPLC) was used to separate 4-MU and its glucuronide. In vitro–in vivo extrapolation (IV–IVE) was employed to predict in vivo inhibition situation.Results: Cryptotanshinone inhibited UGT1A7 and UGT1A9 with IC50 values of 1.91 ± 0.27 and 0.27 ± 0.03 μM, respectively. Dihydrotanshinone I inhibited UGT1A9-catalyzed 4-MU glucuronidation reaction with the IC50 value of 0.72 ± 0.04 μM. The inhibition of cryptotanshinone towards UGT1A7 and UGT1A9 was best fit to competitive inhibition type, and UGT1A9 was non-competitively inhibited by dihydrotanshinone I. Using in vitro inhibition kinetic parameters (Ki) and in vivo maximum plasma concentration (Cmax) of cryptotanshinone and dihydrotanshinone I, the change of area-under-the-concentration–time curve (AUC) was predicted to be 0.4–4.2%, 3.7–56.3%, and 0.6–6.4% induced by cryptotanshinone and dihydrotanshinone inhibition towards UGT1A7 and UGT1A9, respectively.Discussion and conclusion: The inhibitory effects of tanshinones towards important UGT isoforms were evaluated in the present study, which provide helpful information for exploring the mechanism of danshen–clinical drugs interaction.
研究领域:
药理学
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中药学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2020
·
IF 3.565
Yadong Liu,Fanlu Lin,Yaodong Chen,Rui Wang,Jiannan Liu,Yinshan Jin,Ruihua An
Cryptotanshinone (CTT), extracted from the root of Salvia miltiorrhiza Bunge (Danshen), exhibits activities against a variety of human cancers in vitro and in vivo . The purpose of this study was to investigate the potential inhibitory effect of CTT on bladder cancer. In this study, we found that CTT inhibited bladder cancer cell proliferation, migration, and invasion and promoted apoptosis. In addition, CTT modulated the expression of proteins via the PI3K/AKT pathway, and the inhibition of PI3K/AKT signalling was due to induction of PTEN expression. Taken together, the results of the present study demonstrated the anticancer effect of CTT on bladder cancer cells, which might be associated with the downregulation of PI3K/AKT/mTOR and NF-κB signalling pathway proteins, and this inhibition was mediated by the induction of PTEN.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
PLoS One
·
2016
·Vol. 11
·期 7
·e0159967
·
IF 3.057
Zhenwei Yu,Hongyan Lv,Gang Han,Ke Ma
The aim of this study was to develop ethosomes loaded with cryptotanshinone (CPT) and formulate them as a topical gel for the treatment of acne. Ethosomes were prepared and evaluated for vesicle size, CPT loading and encapsulation efficiency. Optimized ethosomes were formulated as Carbomer 974 gels and compared with conventional hydroethanolic gels for transdermal permeation and skin deposition in vitro . The anti-acne activity and skin irritation of the gel was investigated in rabbits. Optimized ethosomes had an average vesicle size of 69.1 ± 1.9 nm with CPT loading and encapsulation efficiency of 0.445 ± 0.007 mg/mL and 40.31 ± 0.67%, respectively. The transdermal flux and skin deposition of the optimized ethosomal gel were 2.5- and 2.1-times those of conventional gels. The ethosomal gel revealed better anti-acne effect with only slight skin irritation. This study demonstrates that ethosomal formulation is an effective dermal delivery system for CPT, and that CPT ethosomal gels are promising future acne treatments.
研究领域:
药剂学
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皮肤病学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
International Journal of Applied Ceramic Technology
·
2018
·Vol. 15
·期 4
·938-946
·
IF 1.165
Huan Zhou,Yaping Bi,Mengmeng Yang,Wenjie Wang,Xinye Ni,Defeng Xu
In current work, solid dispersions (SDs) of Cryptotanshinone (CPT) using mesoporous magnesium phosphates (MgPs) as the dispersing carrier (CPT-MgPs SDs) were prepared, characterized, and evaluated. Three mesoporous MgPs (MgP, MgP-Vc, and MgP-Triton) with different phases and morphology were hydrothermally synthesized first. After that, they were combined with CPT to prepare SDs by an ethanol-based solvent evaporation method. It was observed that the large CPT crystals were transformed into amorphous micro-molecular particles and well dispersed in MgPs nanoparticles after the solvent evaporation procedure. In addition, all MgPs were self-assembled into microspherical agglomerates of palate-like particles. The dissolution studies of CPT from MgPs indicated that 1) the dissolution of CPT from SDs can be improved on comparison to pure CPT, 2) MgP is the best among all carrier tested, but still not satisfactory. In addition, 2 other phenomena about CPT-MgP SD were observed. One was that an apparent increasing trend is seen between the MgP weight ratios and the dissolution rate of CPT. The other one was that MgP can be a pH responsive carrier to tailor the dissolution behavior of CPT. Development of promising SD with CPT solubility improvement, pH responsibility, and sustained drug release ability is still deserved in future.
研究领域:
药剂学
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材料科学
✓ 已验证
DOI
高影响因子
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
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心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SOLUTION CHEMISTRY
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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
Molecular Medicine Reports
·
2017
·Vol. 16
·期 6
·9361-9366
·
IF 1.692
Weixin Zhu,Weihong Qiu,Ailan Lu
Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT‑pretreated rats presented declined phosphoinositide 3‑kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl‑2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti‑apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT‑eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Nana Gao,Zongyu Huang,Jianjie Xie,Shuang Gao,Biaobiao Wang,Huicong Feng,Cuifen Bao,He Tian,Xia Liu
Ethnopharmacological relevance The Cryptotanshinone (CT) is a kind of Chinese medicine extracted from salvia miltiorrhiza, which has various pharmacological activities and is widely used in the treatment of diseases. Aim of the study The objective is to delve into the mechanism by which cryptotanshinone (CT) exerts its effects on rats with the middle cerebral artery occlusion/reperfusion (MCAO/R) model. Additionally, it aims to further assess the interplay between inflammation and oxidative stress, along with the underlying mechanism of CT's anti-ferroptosis function. Materials and methods We constructed the middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats. The effects of cryptotanshinone (CT) were evaluated using 2,3,5 - triphenyltetrazolium chloride (TTC) staining, behavioral assays, immunofluorescence, hematoxylin - eosin (HE) staining, and Nissl staining. Additionally, in vitro, cell viability was assessed by the Cell Counting Kit - 8 (CCK - 8) assay following experimental dosing. Oxygen - glucose deprivation/oxidation (OGD/R) models were established in PC12 and BV2 cells. Flow cytometry was employed to detect cellular reactive oxygen species (ROS) expression. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-px), andMitochondrial Membrane Potential Assay Kit with JC-1(JC-1) were measured using biochemical methods. Inflammatory factor levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Immunoblotting was used to detect the levels of rat phosphatidylinositol 3 - kinase (PI3K), phosphorylated-PI3K (P-PI3K), protein kinase B (AKT), phosphorylated - AKT (P-AKT), nuclear factor erythroid 2related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). Results In rats with the MCAO/R model, CT demonstrated the ability to decrease ROS levels, enhance the activity of glutathione (GSH), mitigate inflammation, augment the activity of glutathione peroxidase 4 (GPX4), inhibit ferroptosis, safeguard neurons, and facilitate the restoration of nerve function. Results from network pharmacology indicated that the action of CT might be mediated via the PI3K/Akt signaling pathway. Simultaneously, in-vivo investigations revealed that CT curbs ferroptosis through the PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathways. Conclusion CT can inhibit ferroptosis by inhibiting the vicious cycle between oxidative stress and inflammation, protect neurons and promote motor function recovery.
研究领域:
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Kai Liu,Bolin Zhao,Zihao Sun,Nini Luo,Xiaofang Li
Liver fibrosis is characterized by the aberrant accumulation of extracellular matrix (ECM) components, primarily due to the persistent activation of hepatic stellate cells (HSCs). It is well-known that chronic liver inflammation from various etiologies leads to hepatocellular damage, which activates HSCs, initiating and exacerbating fibrosis. This presents a significant challenge for therapeutic interventions aimed at restoring ECM balance. Here, we present CPT-pH@RLs, a novel drug delivery system consisting of pH-sensitive liposomes modified with erythrocyte membranes (RBCm), designed to deliver cryptotanshinone to the liver. The results of cellular uptake and real-time in vivo imaging indicate that the modification of RBCm reduces the uptake of CPT-pH@RLs by macrophages and prolongs the in vivo cycling time of these particles. CPT-pH@RLs effectively reduce liver inflammation by inhibiting secretion of interleukin-1β (IL-1β). Moreover, they improve liver function, decrease ECM deposition, and alleviate liver fibrosis. Our findings demonstrate that CPT-pH@RLs represent a safe and effective passive targeting drug delivery system for anti-inflammatory and ECM normalization therapies, offering a promising approach for the reversal of liver fibrosis.
研究领域:
药理学
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生物医学工程
·
肝脏病学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Tao Zhang,Xianmin Shi,Yanjuan Huang,Yujun Gong,Yuanfeng He,Danni Xiao,Shengzhi Wang,Chunshun Zhao
Postoperative abdominal adhesions (PAA) are common diseases following abdominal surgery and can cause various serious complications. The excessive inflammation and oxidative stress are the main causes of PAA formation. Herein, we developed a nanomicellar hydrogel, OFu/HF@CTS, composed of oxidized fucoidan (OFu) and cryptotanshinone (CTS)-loaded hydrazine-functionalized pluronic F127 nanomicelles (HF127@CTS) for the effective prevention of PAA. The hydrogels exhibited satisfactory viscoelasticity, rapid self-healing ability, and good tissue adhesion properties, and were able to slowly release CTS for one week, with a cumulative release rate of 80 % on the 7th day. Additionally, the hydrogels could effectively reduce fibroblast cells and protein adhesions due to the high negative charge of OFu and have good biocompatibility towards RAW 264.7 and L929 cells. Moreover, CTS released from OFu/HF@CTS could efficiently reduce oxidative stress in macrophages and promote M1 macrophages polarized to M2 phenotype to relieve inflammation. In vivo results showed that OFu/HF@CTS hydrogel had good biodegradability and biosafety, and could effectively reduce PAA formation in a rat cecum-abdominal wall abrasion model through the mechanism of alleviating oxidative stress and inflammation, regulating fibrinolysis, and inhibiting fibrosis. This work highlights the therapeutic potential of drug-loaded nanomicellar hydrogels as a preventive strategy for PAA in clinical applications.
研究领域:
生物材料学
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药剂学
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医学
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产品关联
DOI
PubMed
高影响因子
FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
·
2023
·Vol. 61
·期 2
·109-122
·
IF 1.5
Jiahui Han Di Jia Hao Yao Ting Lv Xi Xu Xin Ge
Introduction. Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. Material and methods. Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. Results. H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activity were suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. Conclusions. The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.
研究领域:
药理学
·
病理生理学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2020
·
IF 5.893
Huan Wang,Zhe Liu,Lingnan Guan,Jiankang Li,Siyi Chen,Wenying Yu,Maode Lai
The constitutive activation of signal transducer and activator of transcription 3(STAT3) is associated with aggressive development and metastasis in colorectal cancer (CRC), but STAT3-targeting drugs remain elusive in clinic. Here, structure-based strategy was used to remodel the natural compound cryptotanshinone into a more effective STAT3 inhibitor LYW-6. Using the Biolayer Interferometry assay, we observed that LYW-6 exhibited specific interactions with STAT3(KD = 6.6 ± 0.7 μM). Western blot analysis and electrophoretic mobility shift assays (EMSA) showed that LYW-6 inhibited the phosphorylation of STAT3 tyrosine 705 (Tyr-705) and had slight effects on STAT1 and STAT5 phosphorylation. Western blot analysis on the upstream kinases of STAT3 confirmed that the inhibitory mechanism on p-STAT3 was independent of upstream kinases. Further investigation demonstrated that LYW-6 downregulated the expression of downstream oncogenes to inhibit cell viability, cell cycle development, and potently increased cell apoptosis in human CRC cells. The invasion and metastasis linked signaling was also blocked by LYW-6 treatment. LYW-6 was found to reduce the metastasis foci in lung on tail-lung metastasis models. In addition, it was observed that LYW-6 markedly diminished STAT3 phosphorylation in tumor tissue and significantly inhibited tumor growth on xenograft models. Tumor development on chemically-induced colorectal cancer model also significantly inhibited by LYW-6 treatment. These findings provided adequate evidence that STAT3 inhibitor LYW-6 might be a potential candidate agent for CRC treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
✓ 已验证
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）