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Zheng C.-S.,Fujian Academy of Integrative Medicine | Zheng C.-S.,Fujian University of Traditional Chinese Medicine | Xu X.-J.,Fujian Academy of Integrative Medicine | Xu X.-J.,Peking University | And 7 more authors.
Experimental and Therapeutic Medicine | Year: 2013

The herb pair comprising Salvia miltiorrhiza (SM) and Panax notoginseng (PN) has been used as a classical formula for cardiovascular diseases (CVDs) in China and in western countries. However, the pharmacology of SM and PN in this herb pair has not been fully elucidated. The aim of this study was to compare the mechanisms of SM and PN at the molecular level for the treatment of CVDs. We used a systems pharmacology approach, integrating ligand clustering, chemical space, docking simulation and network analysis, to investigate these two herbal medicines. The compounds in SM were attached to clusters 2, 3, 5, 6, 8 and 9, while the compounds in PN were attached to clusters 1, 2, 4, 5, 6, 7, 8 and 10. The distributions of chemical space between the compounds from SM and PN were discrete, with the existence of small portions of overlap, and the majority of the compounds did not violate 'Lipinski's rule of five'. Docking indicated that the average number of targets correlated with each compound in SM and PN were 5.0 and 3.6, respectively. The minority nodes in the SM and PN drug-target networks possessed common values of betweenness centrality, closeness centrality, topological coeffcients and shortest path length. Furthermore, network analyses revealed that SM and PN exerted different modes of action between compounds and targets. These results suggest that the method of computational pharmacology is able to intuitively trace out the similarities and differences of two herbs and their interaction with targets from the molecular level, and that the combination of two herbs may extend their activities in different potential multidrug combination therapies for CVDs.


Yi J.,Fujian Institute of Education | Liao F.-P.,Fujian Academy of Integrative Medicine | Zheng W.-W.,Fujian Academy of Agricultural science
Chinese Traditional and Herbal Drugs | Year: 2013

Objective: To provide the DNA molecular marker for the identification of Pseudostellaria heterophylla from the different idioplasms by analysis of rDNA ITS sequences. Methods: PCR amplification, cloning, and sequencing were carried out using specified primer, and the rDNA ITS base sequences were compared. Results: The ITS mutation extension was 623-624 pb among nine idioplasms of P. heterophylla. Thereinto, the ITS-1 was 224 pb and its G + C content was 52.91%-54.26%, the 5.8S rDNA was 155 bp and its G + C content was 54.49%-55.13%, the ITS-2 was 244-245 bp and its G + C content was 55.55%-56.41%. There were 17 mutation sites (2.72%) in the whole ITS sequences. There were 7, 7, and 3 mutation sites in ITS1, ITS2, and 5.8S, respectively. The different idioplasms had a number of specific single nucleotide mutation sites. Their homologies with each other were upwards 99.9% and their sequence genetic distances were 0.003-0.013. These results showed that the mutation in species from different producing areas and idioplasms was within no more than one species. Conclusion: The mutation of ITS sequences could be used to authenticate P. heterophylla from different idioplasms.


Li Z.,Fujian Academy of Integrative Medicine | Hu H.,Fujian Academy of Integrative Medicine | Lin R.,Fujian Academy of Integrative Medicine | Mao J.,Fujian Academy of Integrative Medicine | And 6 more authors.
International Journal of Molecular Medicine | Year: 2014

Gua Lou Gui Zhi decoction (GLGZD), a traditional Chinese medicine consisting of different herbal medicines, has been used for centuries in the treatment of muscular spasticity following stroke, epilepsy or spinal cord injury. However, the precise mechanisms involved remain poorly understood. In the present study, we investigated the neuroprotective effects of GLGZD on glutamate-induced apoptosis in cultured BV-2 cells, as well as the underlying mechanisms. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to assess the viability of the cells. An Annexin V/propidium iodide (PI) assay was utilized to analyze cellular apoptosis. Mitochondrial membrane potential (MMP) was evaluated by flow cytometry and laser scanning confocal microscopy. The gene and protein expression of the apoptosis-related genes, Bcl-2 and Bax, was analyzed by RT-PCR and western blot analysis, respectively. Furthermore, the expression of cleaved caspase-3 protein was detected by immunofluorescence. Glutamate treatment induced the loss of BV-2 cell viability, which was associated with an increase in the apoptotic rate, as well as an increase in the Bax/Bcl-2 ratio and the extracellular levels of cleaved caspase-3. Treatment with GLGZD significantly reversed these phenotypes, with its maximum protective effects observed at the concentration of 1,000 μg/ml. These results indicate that GLGZD protects BV-2 cells from glutamate-induced cytotoxicity. These protective effects may be ascribed to its anti-apoptotic activities, in part, associated with the decrease in the Bax/Bcl-2 ratio and caspase-3 expression, as well as with the stability of high mitochondrial membrane potential.


Chen Z.,Fujian Agriculture and forestry University | Xu Y.,Fujian Agriculture and forestry University | Qi Z.,Fujian Academy of Integrative Medicine | Zho J.,Xiamen University
Medical Engineering and Physics | Year: 2015

Sclerosis rim surrounding the necrotic area is commonly found in necrotic femoral head, but the biomechanical function of sclerosis rim has received relatively little attention. Little is known about the formation and natural history of sclerosis rim. In the present work, we assume that the necrotic change may trigger bone remodeling process in the femoral head, which took place according to Huiskes' bone remodeling model incorporated with the FE simulations as described earlier. We then investigate the function of sclerosis rim as a mechanical supporter in delaying further collapse of the femoral head based on our sclerotic rim model. The main tasks of this study are: (1) simulation of the density distribution in the necrotic femoral head after bone remodeling; (2) calculation of maximal von Mises stress in the subchondral bone of the weight-bearing area of the femoral head over the necrotic area before and after bone remodeling. Results show that the sclerotic rim is, from the biomechanical point of view, an adaptive response to the decrease in elastic modulus of the femoral head, and that the sclerotic rim that acts as a compensatory structural reinforcement can usually significantly reduce the maximal stress in the subchondral bone when the lesion is small, but not when the lesion is large. © 2015 IPEM.


PubMed | Xiamen University, Fujian Academy of Integrative Medicine and Fujian Agriculture and forestry University
Type: Journal Article | Journal: Medical engineering & physics | Year: 2015

Sclerosis rim surrounding the necrotic area is commonly found in necrotic femoral head, but the biomechanical function of sclerosis rim has received relatively little attention. Little is known about the formation and natural history of sclerosis rim. In the present work, we assume that the necrotic change may trigger bone remodeling process in the femoral head, which took place according to Huiskes bone remodeling model incorporated with the FE simulations as described earlier. We then investigate the function of sclerosis rim as a mechanical supporter in delaying further collapse of the femoral head based on our sclerotic rim model. The main tasks of this study are: (1) simulation of the density distribution in the necrotic femoral head after bone remodeling; (2) calculation of maximal von Mises stress in the subchondral bone of the weight-bearing area of the femoral head over the necrotic area before and after bone remodeling. Results show that the sclerotic rim is, from the biomechanical point of view, an adaptive response to the decrease in elastic modulus of the femoral head, and that the sclerotic rim that acts as a compensatory structural reinforcement can usually significantly reduce the maximal stress in the subchondral bone when the lesion is small, but not when the lesion is large.


Chen Z.-P.,Fujian Agriculture and forestry University | Qi Z.-X.,Fujian Academy of Integrative Medicine
Yiyong Shengwu Lixue/Journal of Medical Biomechanics | Year: 2012

Objective: To explore the effect of avascular necrosis cystic degeneration on distribution of bone density. Methods: Based on the bone reconstruction model of Weinans and Huiskes, bone density distribution in normal femoral head and in femoral head with avascular necrosis cystic degeneration were calculated by finite element analysis. Results: (1) The medial system of lamellae, lateral system of lamellae, intertrochanteric arch and Ward's triangle were generated on the normal proximal femur under simulation. (2) If a primary cystic degeneration occurred, a secondary cystic area would appear below the primary one and its bone density would decrease dramatically with the primary cystic area increased. Cystic degeneration would also change the femoral bearing truss system. Conclusions: (1) Wolff's law on bone remodeling is consistent with modern topology optimization theory. (2) If cystic degeneration appeared due to avascular necrosis of the femoral head, it should be treated timely to prevent the secondary cystic degeneration and collapse of the femoral head.


Song J.,Chinese Academy of Sciences | Chen W.-Y.,Fujian University of Traditional Chinese Medicine | Wu L.-Y.,Fujian University of Traditional Chinese Medicine | Zheng L.-P.,Fujian Academy of Integrative Medicine | And 4 more authors.
Chinese Journal of Integrative Medicine | Year: 2012

Objective: To study the angiogenesis modulation mechanism of Xuefu Zhuyu Decoction on the endothelial cell line ECV304. Methods: ECV304 cells were treated with 2.5% Xuefu Zhuyu Decoctioncontaining serum (XFZYD-CS) for 24 h, 48 h or 72 h. Thiazolyl blue tetrazolium bromide (MTT), fluorescence activating cell sorter (FACS), migration, adhesion and in vitro tube formation assays were conducted to confirm an angiogenesis effect of XFZYD at 3 time points. An analysis of angiogenesis regulator profiles was performed at 3 times with real-time polymerase chain reaction (RT-PCR) superarray. Results: At 48 h, XFZYD-CS induced ECV304 significantly improved cell viability, number in S phase, migration, adhesion and tube formation. At 24 h and 72 h, only cell migration was elevated. Microarray results showed that the expression of 27 angiogenesis-related genes was changed. Conclusion: XFZYD-CS treatment induced angiogenesis on ECV304 cells with significant cellcular changes occurring at 48 h and genetic changes as early as 24 h. © 2012 The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg.


Zhao J.-Y.,Fujian Academy of Integrative Medicine | Zhao J.-Y.,Fujian University of Traditional Chinese Medicine | Chen Z.-H.,Fujian Guizhentang Pharmaceutical Co. | Lin W.,Fujian Academy of Integrative Medicine | And 4 more authors.
Chinese Journal of Integrative Medicine | Year: 2014

Objective: To evaluate the effect of Bear Bile Powder (BBP) on the growth and apoptosis of HepG2 human hepatocellular carcinoma cells, and investigate the possible molecular mechanisms mediating its anti-cancer activity. Methods: HepG2 cells were treated with 0.4-1.0 mg/mL of BBP for 24, 48 and 72 h. The viability of HePG2 cells was determined by MTT assay. Cellular morphology was observed via phase-contrast microscopy. Fluorescence-activated cell sorting analysis with Annexin-V/propidium idodide and 5,5′,6,6′-tetrachloro- 1,1′,3,3′-tetraethyl-benzimidazol-carbocyanine iodide (JC-1) staining was performed to determine cell apoptosis and the loss of mitochondrial membrane potential, respectively. Activation of caspase-9 and -3 was evaluated by a colorimetric assay. Results: The treatment with 0.4-1 mg/mL of BBP for 24, 48, or 72 h respectively reduced cell viability significantly by 7%-60%, 20%-90% or 25%-98%, compared with the untreated control cells (P<0.01). In addition, BBP treatment induced morphological changes in HepG2 cells. Furthermore, after treated with 0, 0.4, 0.6, 0.8 and 1.0 mg/mL of BBP, apoptosis cells (including early and late apoptotic cells) were 18.0%±1.3%, 34.9%±2.2%, 33.9%±2.8%, 37.4%±2.8% and 46.0%±2.5%, respectively (P<0.05); and the percentage of cells with reduced JC-1 red fluorescence were 6.6%±0.8%, 8.5%±0.8%, 13.5%±1.6%, 17.6%±2.3% and 46.7%±3.6%, respectively (P<0.01). Finally, BBP treatment significantly and dose-dependently induced activation of both caspase-9 and caspase-3 in HepG2 cells (P<0.05). Conclusion: BBP could inhibit the growth of HepG2 hepatocellular cancer cells through mitochondrion-mediated apoptosis, which may, in part, explain its anti-cancer activity. BBP may be a potential novel therapeutic agent for the treatment of hepatocellular carcinoma. © 2013 Chinese Association of the Integration of Traditional and Western Medicine and Springer-Verlag.


Wu Y.S.,Fujian Academy of Integrative Medicine
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2010

To investigate the effects of Jiangu granule containing serum (JGG-serum) on the cyclins in rat's osteoblast at G1 phase. Osteoblasts isolated by enzymatic digestion from SD rats were cultured and intervened with JGG-serum or normal saline (as control) respectively. Cell generation cycle was detected by flow cytometry, and expressions of Cyclin D1, cyclin-dependent kinase 4 (CDK4), oncogene protein (P21) in the osteoblast were detected dynamically using immuno-cytochemical and RT-PCR technique. As compared with the control, the cell generation cycle and cell proliferation were proceeding quicker in the JGG-serum (20%) intervention group; with higher protein and mRNA expressions of Cyclin D1 and CDK4, as well as much lowered expressions of P21 in nuclei of osteoblast detected at all time points (24 h, 48 h and 72 h after treatment, P < 0.05 or P < 0.01). JGG-serum can adjust the G1 phase cyclins in osteoblast cultured in vitro, increase the mRNA and protein expressions of Cyclin D1 and CDK4, and inhibit P21 expression, so as to accelerate the proliferation of osteoblast.


PubMed | Fujian Academy of Integrative Medicine
Type: Journal Article | Journal: Chinese journal of integrative medicine | Year: 2015

To evaluate the effect of bear bile powder (BBP) on angiogenesis, and investigate the underlying molecular mechanisms.A chick embryo chorioallantoic membrane (CAM) assay was used to evaluate the angiogensis in vivo. Human umbilical vein endothelial cells (HUVECs) were treated with 0, 0.25, 0.5, 0.75, and 1.0 mg/mL of BBP for 24, 48 and 72 h, respectively. The 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the viability of HUVECs. Cell cycle progression of HUVECs was examined by fluorescence-activated cell sorting (FACS) analysis with propidium iodide staining. HUVEC migration was determined by wound healing method. An ECMatrix gel system was used to evaluate the tube formation of HUVECs. The mRNA and protein expression of vascular endothelial growth factor (VEGF)-A in both HUVECs and HepG2 human cells were examined by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively.Compared with the untreated group, BBP inhibited angiogenesis in vivo in the CAM model (P< 0.01). In addition, treatment with 0.25-1 mg/mL of BBP for 24, 48, or 72 h respectively reduced cell viability by 14%-27%, 29%-69% and 33%-91%, compared with the untreated control cells (P< 0.01). Additionally, BBP inhibited the proliferation of HUVECs via blocking the cell cycle G to S progression, compared with the S phase of untreated cells 48.05% 5.00%, 0.25-0.75 mg/mL BBP reduced S phase to 40.38% 5.30%, 36.54 4.50% and 32.13 3.50%, respectively (Pglt; 0.05). Moreover, BBP inhibited the migration and tube formation of HUVECs, compared with the tube length of untreated cells 100% 12%, 0.25-0.75 mg/mL BBP reduced the tube length to 62% 9%, 43% 5% and 17% 3%, respectively (p< 0.01). Furthermore, BBP treatment down-regulated the mRNA and protein expression levels of VEGF-A in both HepG2 cells and HUVECs.BBP could inhibit the angiogenesis by reducing VEGF-A expression, which may, in part, explain its anti-tumor activity.

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