Turkish Journal of Gastroenterology
·
2025
·Vol. 36
·期 7
·431
·
IF 1.6
Ying Jiang,Xinjie Wang,Zhenyang Wang,Shengliang Zhang,Jianhua Wang,Xianglong Wang,Yang Zhang
Background/Aims: Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy that carries a dismal prognosis. Tanshinone IIA (Tan-IIA) is involved in the regulation of N6-methyladenosine (m6A) modification and plays an anti-tumor role in HCC, but whether Tan-IIA regulates HCC by mediating m6A modification is unclear. Methods and Materials: Cell apoptosis, invasion, proliferation, viability, and stemness were estimated with flow cytometry, transwell, 5-ethynyl-2’-deoxyuridine, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, and sphere-forming assays. Methyltransferase-like 14 (METTL14) and 3 (METTL3) mRNA and protein levels were detected with reverse transcription-quantitative polymerase chain reaction and western blotting. Total m6A levels were measured using an m6A RNA methylation quantification kit. A possible regulation of tribbles pseudokinase-3 (TRIB3) expression by METTL3 in an m6A-modified manner was predicted through RM2Target and SRAMP and verified by m6A methylated RNA immunoprecipitation (MeRIP) and RIP. Mouse xenograft models assessed the action of Tan-IIA in HCC tumorigenesis. Results: Tanshinone IIA restrained HCC cell viability, proliferation, invasion, and stemness, and induced HCC cell apoptosis invitro, as well as repressed tumor growth in xenograft models. METTL3 and TRIB3 were upregulated in HCC samples and downregulated in Tan-IIA-treated HCC cells and xenograft tumors. METTL3 facilitated HCC cell viability, proliferation, invasion, and stemness by enhancing TRIB3 mRNA stability through m6A modification. Tan-IIA played its role by downregulating TRIB3, and Tan-IIA mediated TRIB3 expression by METTL3. Conclusion: Tanshinone IIA restrained HCC progression by regulating METTL3-mediated m6A modification of TRIB3 mRNA, offering evidence to support the clinical translation of Tan-IIA.
研究领域:
肿瘤学
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分子生物学
·
表观遗传学
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药理学
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转化医学
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产品关联
DOI
PubMed
高影响因子
Biomedicines
·
2023
·Vol. 11
·期 12
·3291
·
IF 4.7
Jingjing Sun,Wei Chen,Zheng Zhou,Xin Chen,You Zuo,Jiaqian He,Hairong Liu
(1) Background: Osteoarthritis (OA) is a crippling condition characterized by chondrocyte dedifferentiation, cartilage degradation, and subsequent cartilage defects. Unfortunately, there is a lack of effective medicines to facilitate the repair of cartilage defects in OA patients. In this study, we investigated the role of lncRNA NEAT1_2 in maintaining the chondrocyte phenotype and identified tanshinone IIA(TAN) as a natural medicine that enhances NEAT1_2 levels, resulting in efficient cartilage regeneration under inflammatory cytokines. (2) Methods: The transcriptional levels of NEAT1_2 and cartilage phenotype-related genes were identified by RT-qPCR. The siRNA interference approach was utilized to silence NEAT1_2; the Alamar Blue assay was performed to determine chondrocyte viability under inflammatory conditions. To evaluate the concentrations of collagen type II and glycosaminoglycans distributed by chondrocytes in vitro and in vivo, immunohistochemical staining and Safranin O staining were used. (3) Results: IL-1β suppresses NEAT1_2 and genes related to the chondrocytic phenotype, whereas TAN effectively upregulates them in a NEAT1_2-dependent manner. Consistently, TAN alleviated chondrocyte oxidative stress inhibited cartilage degradation by modulating the relevant genes and promoted efficient cartilage regeneration in vitro and in vivo when chondrocytes are exposed to inflammatory cytokines. (4) Conclusions: TAN enhances the expression of NEAT1_2 inhibited by IL-1β and affects the transcription of chondrocytic phenotype-related genes, which promotes cartilage regeneration in an inflammatory environment.Keywords:osteoarthritis;tanshinone IIA;NEAT1_2;cartilage defects repair;inflammatory
研究领域:
风湿病学
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药理学
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分子生物学
·
再生医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Haidong Chen,Yimei Li,Dexuan Chen,Yong Fang,Xuchu Gong,Kaikai Wang,Chaoqun Ma
Chronic and infected wounds, particularly those caused by bacterial infections, present significant challenges in medical treatment. This study aimed to develop a novel nanoparticle formulation to enhance wound healing by combining antimicrobial and photothermal therapy using albumin as a carrier for Tanshinone IIA and the near-infrared photothermal agent IR780. The nanoparticles were synthesized to exploit the antimicrobial effects of Tanshinone IIA and the photothermal properties of IR780 when exposed to near-infrared laser irradiation. Characterization of the nanoparticles was performed using Transmission Electron Microscopy (TEM) and spectroscopic analysis to confirm their successful synthesis. In vitro antibacterial activity was evaluated using cultures of methicillin-resistant Staphylococcus aureus (MRSA), and in vivo efficacy was tested in a mouse model of MRSA-infected wounds. Wound healing progression was assessed over 16 days, with statistical analysis performed using two-way ANOVA followed by Tukey’s post-hoc test. The nanoparticles demonstrated significant photothermal properties, enhancing bacterial eradication and promoting the controlled release of Tanshinone IIA. In vitro studies showed superior antibacterial activity, especially under photothermal activation, leading to a substantial reduction in bacterial viability in MRSA cultures. In vivo, nanoparticle treatment combined with near-infrared laser irradiation significantly improved wound closure rates compared to controls and treatments without photothermal activation. By the 16th day post-treatment, significant improvements in wound healing were observed, highlighting the potential of the combined photothermal and pharmacological approach. These findings suggest that albumin-loaded nanoparticles containing Tanshinone IIA and IR780, activated by near-infrared light, could offer an effective therapeutic strategy for managing chronic and infected wounds, promoting both infection control and tissue repair.
研究领域:
医学
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纳米技术
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2018
·
IF 2.297
Chao Luo,Weibin Wu,Xinyu Lin,Yaoqi Li,Kai Yang
The objective of this study was to develop and evaluate a novel tanshinone IIA (TA)/chitosan (CS) solid dispersion (TA-CS-SD) to improve the bioavailability. Solid dispersion of tanshinone IIA with chitosan was prepared by a pH inversion method via the pH-responsive dissolution property of chitosan matrix. The in vitro dissolution study confirmed dramatically elevated dissolution rate of TA by solid dispersion approach, and the release mechanism exhibited pH-responsive performance. The solid dispersion was characterized by x-ray diffractometry (XRD), differential scanning calorimetry (DSC), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Our results showed that TA existed in the form of microcrystal or superfine crystal in solid dispersion, and the reduction of crystallinity was correlated with the content of CS matrix. In vitro cytotoxicity study was performed in human non-small cell lung cancer A549 cell line by CCK-8 assay. Significant improvement in antitumor activity of TA in TA-CS-SD was achieved compared to the crystalline drug. These results indicated that, compared with free TA, TA-CS-SD demonstrated higher dissolution rate and bioactivity.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Dongdong Wang,Feifei Sun,Chunbo Lu,Peng Chen,Zhaojie Wang,Yuanhao Qiu,Haibo Mu,Zehong Miao,Jinyou Duan
Colorectal cancer is one of the most common types of tumor in the world. Here we developed a lipoic acid esterified polysaccharide (inulin) delivery system for tanshinone IIA to treat colorectal cancer in vitro . The release of tanshinone IIA in the system was highly responsive to glutathione , which is commonly abundant in cancer cells. In addition, this drug delivery system was proliferative to Bifidobacterium longum , the common inhabitant of human intestine. Thus, this strategy might be useful to improve colon cancer therapy efficacy of anticancer drugs and meanwhile promote the growth of beneficial commensal flora in the gut.
研究领域:
药剂学
·
肿瘤学
·
肠道微生物学
✓ 已验证
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
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2024
·
IF 4.2
Chunyan Cai,Kai Liu,Dejun Yang,Jijiao Wu,Zhaolei Peng,Yulin Wang,Jingjing Xi,Fan Xie,Xiaofang Li
Tanshinone IIA (TSIIA) is a lipid-soluble pharmacological constituent extracted from the Salvia miltiorrhiza with anti-hepatic fibrosis properties. However, its clinical use has been limited due to its poor water solubility and oral bioavailability. In this paper, we constructed a drug delivery system consisting of a drug nanocrystal core and a liposome shell: TSIIA nanocrystals@liposome (TNC@Lipo). This combination can greatly improve the solubility and bioavailability of poorly water-soluble drugs. TNC@Lipo was prepared by ultrasonic method combined with antisolvent method. In order to obtain the optimal TNC, we optimized the formulation ratio and preparation process of TNC by single-factor experiments. The results showed that TNC@Lipo had higher drug loading (27.86 ± 1.55 %) and superior stability. And TNC@Lipo can significantly reversed CCl 4 -induced liver fibrosis in mice compared with free-TSIIA. In conclusion, this study provides a new approach for the clinical application of TSIIA.
研究领域:
药剂学
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肝脏病学
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纳米医学
✓ 已验证
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
·
神经科学
·
药物递送系统
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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
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2025
·Vol. 2025
·期 1
·8349248
·
IF 4.2
Yuanjie Wu,Yuntian Zhang,Xike Wu,Ziyan Zhang,Junhui Shen,Nan Tian,Chunlei Fan
This study investigated the effects of tanshinone IIA combined with rutin and squalene (RTS) on atherosclerosis (AS) associated with hyperlipidemia and the underlying mechanisms. Female New Zealand rabbits were subjected to a hyperlipidemia and AS model. Treatment with RTS for 4 weeks reduced the weight, and some serum lipid levels include serum TC, serum TG, serum LDL-C. RTS also improved lesions of the liver and aorta. In vitro analyses showed that RTS significantly activated LDLR-mediated hepatic lipid endocytosis, but blocking LDLR activation with si-SREBP2 attenuated the therapeutic effect, which demonstrated that RTS can activate the SREBP2/LDLR pathway mediating liver clearance of blood lipids. This study highlights the therapeutic potential of RTS in hyperlipidemia and AS. As a convenient form of a combination drug, RTS has shown considerable potential in the improvement of hyperlipidemia combined with AS.
研究领域:
药理学
·
心血管病学
·
分子生物学
✓ 已验证
产品关联
DOI
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
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