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Efficacy and safety of ACEI plus tanshinone for acute exacerbation of pulmonary heart disease: a meta-analysis

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Journal of Chinese Pharmaceutical Sciences 2022年第11期31卷 853-865页

作者： Min Li Lulu Chang Xiangfeng Yue Shuzhang Du Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina

Acute exacerbation of pulmonary heart disease(AECPHD) is life-threatening. Conventional therapy plus angiotensinconverting enzyme inhibitors(ACEI) is not always practical. Recent trials have suggested the beneficial effects of the combination of ACEI and tanshinone on AECPHD. In the present study, we aimed to evaluate its efficacy and safety by meta-analysis systematically. The result indicated that combination of ACEI and tanshinone was more effective than ACEI monotherapy in AECPHD, as represented by treatment efficiency and mean pulmonary arterial pressure, PaCO_(2), and PaO_(2). However, the incidence of adverse events of combined therapy was higher than the control group, while the result of the analysis for adverse events was unstable. Further large-scale, multicenter, and rigorously designed randomized controlled trials(RCT) are needed to evaluate the efficacy and safety of combined therapy.

关键词： Enalapril Captopril tanshinone Meta-analysis AECPHD

tanshinone prevents cancellous bone loss induced by ovariectomy in rats

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Acta Pharmacologica Sinica 2004年第5期25卷 136-142页

作者： Liao CUI2,3, Tie WU3, Yu-yu LIU3, Yi-feng DENG4, Chun-mei AI4, Huai-qing CHEN22Institue of Biomedical Engineering, West China Medical Center, Sichuan University, Chengdu 610041, China 3Department of Pharmacology, 4Guangdong Key Laboratory for Research and Development of Natural Drugs,Guangdong Medical College, Zhanjiang 524023 China 四川大学 Chengdu 610041 Department of Pharmacology Guangdong Medical College Zhanjiang 524023 Department of Pharmacology Guangdong Medical College Zhanjing 524023 Guangdong Medical College Guangdong Key Laboratory for Research and Development of Natural Drugs Zhanjiang 524023

AIM: To investigate the skeletal effects of total tanshinone in ovariectomized rats by analyzing cancellous bonehistomorphometry of fourth lumbar vertebrae (LV4) and proximal tibial metaphyses (PTM). METHODS: Four-month-old Sprague-Dawley female rats were sham-operated and treated with vehicle or ovariectomized and treatedwith either vehicle, total tanshinone (200 mgkg-1d-1, equivalent to 35 gkg-1d-1 of tanshinone II A and 16 mgkg -1d-1 ofcryptotanshinone), or 17a-ethynylestradiol (30 gkg-1d-1 as positive treatment group) starting one day post-sur-gery for 10 weeks. Double in vivo fluorochrome labeling was administered to all rats. The undecalcified longitu-dinal LV4 and PTM sections were cut and stained with Goldners Trichrome (4-m thickness) or unstained (8-mthickness) for the bone histomorphometric analysis. RESULTS: A significant decrease in trabecular bone volume(BV/TV) and trabecular number (Tb.N) and a significant increase in osteoclast surface (OCS/BS) and mineralizingsurface (MS/BS) were found in both LV and PTM of vehicle-treated OVX rats compared with sham *** completely prevented the decreases in BV/TV and Tb.N and the increase in OCS/BS in the LV4, andpartially prevented the decreases in BV/TV and Tb.N in the PTM of OVX rats. In addition, tanshinone increasedtrabecular thickness (***) whereas it did not alter MS/BS. Moreover, tanshinone had no effect on uterine weightand body weight of OVX rats. Estrogen treatment increased BV/TV and Tb.N and decreased OCS/BS, but, alsomarkedly decreased MS/BS and increased uterine weight in OVX rats. CONCLUSION: The current study demon-strated that the adequate supply of tanshinone prevented OVX-induced cancellous bone loss in rats through inhibi-tion of elevated bone resorption.

关键词： tanshinone cryptotanshinone 2-fluoro-17alpha-ethynylestradiol ovariectomy bone and bones osteoclasts osteoporosis histocytochemistry morphology

tanshinone IIa antagonizes spinal ischemia/reperfusion injury by interfering with upstream glutamic acid factors

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Neural Regeneration Research 2010年第20期5卷 1573-1577页

作者： Li Zhang Xiang Lin Weinan Liu Jianhua Lin School of Traumatology and Orthopedics Fujian University of Traditional Chinese Medicine Fuzhou 350108 Fujian Province China Department of Traumatology and Orthopedics People's Hospital of Fujian University of Traditional Chinese Medicine Fuzhou 350004 Fujian Province China Department of Orthopedics First Affiliated Hospital of Fujian Medical University Fuzhou 350005 Fujian Province China

Based on the hypothesis that upstream factor inhibition results in better treatment effects than downstream factor inhibition,the present study interfered with glutamic acid（Glu）-released upstream factors,such as Glu transporter function and Na＋-K＋-adenosine triphosphatases（ATPase）activity *** with spinal cord ischemia/reperfusion injury received intraperitoneal injections of tanshinone Ila and Glu uptake and Na＋-K＋-ATPase activity were *** showed that tanshinone Ila influenced Glu-released upstream factors following spinal ischemia/reperfusion injury and protected against spinal ischemia/reperfusion injury.

关键词： spinal cord ischemia/reperfusion injury tanshinone glutamic acid transporter Na+-K+-ATPase neural regeneration

Effects of tanshinone on neuropathological changes induced by amyloid β-peptide(1-40)injection in rat hippocampus

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Acta Pharmacologica Sinica 2004年第7期25卷 15-22页

作者： Long-xuan LI2, Jia-pei DAI3, Li-qiang RU4, Guang-fu YIN4, Bin ZHAO Department of Neurology, Affiliated Hospital, Guangdong Medical College, Zhanjiang 524001, China 3The Netherlands Institute for Brain Research, Amsterdam 1105AZ, the Netherlands 4Department of Neurobiology, TongjiMedical College of Huazhong Universityof Science and Technology, Wuhan 430030, China Department of Neurology Affiliated Hospital Guangdong Medical College Zhanjiang 524001 The Netherlands Institute for Brain Research Zhanjiang 524001 Department of Neurobiology Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030

AIM: To investigate the effect of tanshinone (Tan) on the neuropathological changes induced by amyloid β- peptide1-40(Aβ1-40) injection in hippocampus in rats. METHODS: Aβ1-4010 μg was injected bilaterally into the dorsal blade of the dentate gyrus in the hippocampus. The level of acetylcholinesterase (AChE) in hippocampus was evaluated by histochemistry. The expressions of neuronal nitric oxide synthase (nNOS) and inducible form of NOS (iNOS) were detected by immunohistochemistry and Western blot. Aβ1-40-injected rats were treated ig with Tan, the major active ingredient from Salvia miltiorrhiza of Chinese herb extract. RESULTS: The level of AChE positive fibers of each subfield in Aβ1-40-injected hippocampus decreased significantly compared with those of control (P< 0.01). The expression of nNOS was down-regulated whereas the iNOS was up-regulated. After treatment with Tan (50 mg/kg, ig), the changes mentioned above were significantly improved. Moreover, the correlation analysis revealed a significant negative correlation between the area percentage of AChE positive fibers and the number of iNOS positiveneural cellsin CA1,CA2 toCA3 (CA2-3),and dentategyrus (DG)subfields (P<0.01). CONCLUSION: Tan can protect the neuropathological changes induced by Aβ1-40 injection in hippocampus.

关键词： tanshinone amyloid beta-protein acetylcholinesterase nitric oxide synthase hippocampus

Synthesis and Antitumor Activity of tanshinone Analogues

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Chinese Journal of Chemistry 2003年第7期21卷 720-722页

作者：阿吉艾克拜尔.艾萨吕伟蔡俊超 Xinjiang Technical Institute of Physics & Chemistry Chinese Academy of SciencesUrumqiXinjiang 830011China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 200031China

8,8-Dimethyl-5,6,7, 8-tetrahydrophenanthrene-3, 4-dione (3) and 8,8-dhnethyl-2-(1-hydroxy ethyl)-5,6,7,8-tetrahydrophe-nanthrene-3,4-dione (4), two analogues of the antitumor active tanshinone, were synthesized from anisole. The synthesized compounds 3 and 4 were shown to be highly active against leukemia P-388 cell line as assayed by in vitro MTT method.

关键词： synthesis tanshinone analogues

Synthesis and biological evaluation of novel tanshinone IIA derivatives for treating pain

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Chinese Journal of Natural Medicines 2018年第2期16卷 113-124页

作者： LI Qi-Nan HUANG Zhi-Peng GU Qin-Lan ZHI Zhuo-Er YANG Yu-Han HE Long CHEN Kai-Li WANG Jin-Xin Jiangsu Key Laboratory of Drug Design and Optimization China Pharmaceutical University Nanjing 211009 China Higher Vocational School of Pharmacy，China Pharmaceutical University Nanjing 211009 China

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase(MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound Ⅲ-3(IC_(50) 120 nmol·L^(-1)) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound Ⅲ-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.

关键词： tanshinone IIA:MAGL inhibitors Analgesic activity

Reversing effect of tanshinone on malignant phenotypes of human hepatocarcinoma cell line

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World Journal of Gastroenterology 1998年第4期4卷 45-47页

作者： YUAN Shu-Lan HUANG Ren-Min WANG Xiu-Jie SONG Yi HUANG Guang-Qi Institute of Cancer Research West China University of Medical Sciences Chengdu 610041Sichuan Province China

AIM To study the reversing effect of Chinese drug tanshinone on malignant phenotype of cancer *** Human hepatocarcinoma cell line (SMMC-7721) was treated in vitro with 0.5mg/L tanshinone for 4 days, and variation in cell differentiation was *** The morphology of cancer cells was tended toward well differentiation and cell growth was markedly inhibited. BrdU uptake assay and immunohistochemical stain of PCNA showed that the BrdU labeling rate and PCNA positive rate were lower than the controls, but no difference was found statistically as compared with all transretinoic acid. Flow cytometric assay demonstrated that S phase cells decreased and G0/G1 phase cells increased. Expression of c-myc oncogene protein decreased but the c-fos oncogene protein markedly *** tanshinone could reverse the inducing differentiation in human hepatocarcinoma cells (SMMC-7721). It may become a new prospective inducer of cell differentiation to treat cancers.

关键词： tanshinone liver neoplasms carcinoma,hepatocellular tumor cell,cultured cell line immunohistochemistry proliferation cell nuclear antigen flow cytometry

tanshinone Ⅱ A, the major lipophilic component of Danshen, promotes neuronal differentiation through MAPK42/44 mediated pathways

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中国药理学通报 2015年第B11期31卷 61-62页

作者： ZHAOYu-ming XUPing-xiang XUEMing DeptofPharmacology SchoolofBasicMedicalSciencesCapitalMedicalUniversityBeijing100069

Danshen has been used in stroke treatment for thousands of years in China. However, the underlying mechanism still remains elusive. Neuron loss is the cardinal feature of stroke. Stimulating endogenous neurogene- sis, especially neuronal differentiation, might potentially provide therapeutic effects to these diseases. To interpret Danshen＇ s disease-modifying effects, the effects of tanshinone 11 A （T 11 A）, the major lipophilic component of Danshen, on neuronal differentiation in rat PC12 pheochromocytoma cells and the rat embryonic cortical neural stem cells （NSCs） were observed. PC12 cells and NSCs were incubated with T II A for 7 days. To detect the neu- ronal differentiation, GAP-43 expression was detected by western blots assay and β-tubulin HI expression was de- tected by immunocytochemical staining. Results showed that T Ⅱ A dose-dependently promoted neuronal differentia- tion. T Ⅱ A activated mitogen-activated protein kinase 42/44 （MAPK42/44） and its downstream transcription fac- tor, cAMP response element-binding protein （CREB）. In addition , T Ⅱ A up-regulated the expressions of brain de- rived neurotrophic factor （BDNF） and nerve growth factor （NGF）. The MEK inhibitor and the antagonist to the re- ceptors of NGF and BDNF could partially attenuate the differentiation effects, indicating that MAPK42/44 mediated BDNF and NGF signals were involved in T Ⅱ A＇ s differentiation effects. Caveolin-1 （ CAV-1 ）, the major functional protein of membrane caveolae, plays critical roles in the endocytosis of exogenous materials. CAV1, which was ac-tivated by T Ⅱ A, might help T Ⅱ A transport across cell membrane to initiate its differentiation effects. It was prov- en by the evidences that suppressing the function of caveolin inhibited the differentiation effects of T Ⅱ A. There- fore, it was concluded that T Ⅱ A promoted neuronal differentiation partially through MAPK42/44 mediated B DNF and NEF signals in a caveolae-dependent manner.

关键词： tanshinone Ⅱ A stroke neuronal differentiation mAPK42/44 caveolin-1 BDNF NGF

Preparation and characterisation of solid dispersions of tanshinone ⅡA, cryptotanshinone and total tanshinones

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Asian Journal of Pharmaceutical Sciences 2017年第1期12卷 85-97页

作者： Xifeng Zhai Chunguang Li George Binh Lenon Charlie C.L.Xue Weize Li Traditional&Complementary Medicine Program School of Health SciencesRMIT UniversityBundooraVictoriaAustralia School of Pharmaceutical Sciences Xi’an Medical UniversityXi’anChina Center for Complementary Medicine Research National Institute of Complementary MedicineUniversity of Western SydneyCampbelltown CampusPenrithNew SouthWalesAustralia

Total tanshinones are lipophilic active constituents extracted from Salvia miltiorrhiza *** ⅡA and cryptotanshinone are the major components in total ***, the bioavailability of both compounds is low due to poor water solubility. To enhance the solubility and dissolution rate of tanshinone ⅡA, cryptotanshinone and total tanshinones,three common used hydrophilic carriers including PEG 6000, poloxamer 188 and PVP K30 were used to prepare the solid dispersions at different ratios, respectively. The solid dispersions were characterised by scanning electron microscopy(SEM), differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR). The results of powder X-ray diffraction confirmed the microcrystal state of total tanshinones in solid dispersions and no chemical interaction between total tanshinones and carriers was observed in FTIR spectra. The solubility and dissolution rate of tanshinone ⅡA and cryptotanshinone were significantly increased in all solid dispersions. Regarding tanshinone ⅡA, the solubility and dissolution rate of in solid dispersions prepared with poloxamer 188 were significantly higher than that with PEG 6000 and PVP K30. The higher solubility and dissolution rate of cryptotanshinone were obtained in solid dispersion of PVP K30 than that of PEG 6000 solid dispersions but no significant difference from poloxamer 188 solid dispersions. The results indicate that the superior carrier for preparation of tanshinone ⅡA and total tanshinones solid dispersions is poloxamer 188, and that for cryptotanshinone is PVP K30.

关键词： Cryptotanshinone tanshinone ⅡA Total tanshinones Solid dispersion Dissolution rate