Dian-Dong Li

Chinese Academy of Medical Sciences, Peping, Beijing, China

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Publications (17)25.89 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Salidroside (SAL) is one of main active components of Rhodiola rosea L and possesses diverse pharmacological effects. However, the direct role of SAL in bone metabolism remains elusive. In this study, effects of SAL on osteoblast differentiation of murine pluripotent mesenchymal cell line C3H10T1/2 and osteoblastic cell line MC3T3-E1 were examined. We first identified SAL as a potential BMP2 activator in a cell-based screening assay. SAL (0.5-10 μM) could slightly promote the proliferation and greatly increase the alkaline phosphatase (ALP) activity in both cells. Furthermore, SAL increased the mRNA expressions of osteoblast marker genes in either C3H10T1/2 or MC3T3-E1 cells after treatment for different time. Moreover, the mineralization of C3H10T1/2 cells assayed by Alizarin Red S staining was dose-dependently increased by SAL. Mechanistically, SAL increased the mRNA level of genes involved in the regulation of BMP signaling pathway, including BMP2, BMP6 and BMP7, and enhanced the phosphorylation of Smad1/5/8 and ERK1/2. The osteogenic effect of SAL was abolished by BMP antagonist noggin or by BMP receptor kinase inhibitor dorsomorphin. Further in vivo study demonstrated that SAL reversed bone loss in ovariectomized rats. Collectively, our findings indicate that SAL regulates bone metabolism through BMP signaling pathway.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 09/2013; · 2.99 Impact Factor
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    ABSTRACT: LPS stimulation of macrophages production of IFN-beta plays a key role in innate immunity defending the microbial invasion. In this study, the effect of S632A3 promoting LPS-induced IFN-beta production and the underlying mechanism were investigated, mRNA level was measured by real-time PCR, cytokine production was determined by ELISA, GSK-3beta activity was investigated by kinase assay, protein phosphorylation and expression were evaluated by Western blotting. The results revealed that S632A3 significantly augmented IFN-beta production by LPS-stimulated macrophages. S632A3 inhibition of the activation of GSK-3beta, reduced the threonine 239 phosphorylation of transcription factor c-Jun but increased the total level of c-Jun in LPS-stimulated macrophages. Moreover, small interfering RNA-mediated knockdown of c-Jun level abrogated the ability of S632A3 to augment IFN-beta. The study thus demonstrates S632A3 being a new anti-inflammation lead compound and provides a molecular mechanism by which S632A3 promoted LPS-induced IFN-beta production in macrophages through inhibiting the activation of GSK-3beta.
    Yao xue xue bao = Acta pharmaceutica Sinica 07/2013; 48(7):1113-8.
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    ABSTRACT: To provide a better service for senior health care, we summarized screening studies of traditional Chinese anti-aging materia medica (TCAM). We collected and analyzed literature of TCAM screening studies using the lifespan test and animal models of aging from 1984 to 2012. We found 26 screening methods for TCAM, and 153 single herbs or active ingredients of TCAM that have been screened out during the past 28 years. The cell lifespan test, the fruit fly lifespan test, and D-galactose aging model were the most widely used and intensively studied screening methods. However, the method for establishing the D-galactose aging model needs to be standardized, and the D-galactose aging model cannot completely be a substitute for the normal aging mouse model. Great success has been achieved in screening studies in TCAM. To further improve screening studies in TCAM, we suggest that the D-galactose aging model be incorporated into the lifespan test in the New Drugs of Traditional Chinese Medicine Research Guide.
    Chinese Journal of Integrative Medicine 04/2013; 19(4):243-52. · 1.06 Impact Factor
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    ABSTRACT: Na(+)/K(+)-ATPase targeted cancer therapy has attracted increasing interests of oncologists in lung cancer field. Although multiple anti-cancer mechanisms of cardiac glycosides as Na(+)/K(+)-ATPase inhibitors are revealed, the role of autophagy and related molecular signaling pathway for the class of compounds in human non-small cell lung cancer (NSCLC) cells has not been systematically examined. We herein investigated the anti-cancer effects of two representative cardiac glycosides, digoxin and ouabain, in A549 and H460 cell lines. Both agents caused significant growth inhibition at nanomolar level. The cardiac glycosides were found to induce moderate G(2)/M arrest but not apoptosis at IC(50) level in the NSCLC cell lines. Moreover, autophagy was markedly induced by both agents, as evidenced by the time- and dose-dependent increase of LC3-II, up-regulation of Atg5 and Beclin1, as well as by the observations through acridine orange staining, transmission electron microscopy and quantification of GFP-LC3 fluorescence. Importantly, AMP-activated protein kinase (AMPK) pathway was activated, resulting in mammalian target of rapamycin (mTOR) deactivation during autophagy induction. Moreover, extracellular-signal-regulated kinase 1/2 (ERK1/2) activation was simultaneously found to be involved in the autophagy regulation. Co-treatment with respective inhibitors or siRNAs could either block the autophagic phenotypes and signals, or significantly increase the cellular viability, indicating the drugs-induced autophagy plays tumor-suppressing role. This work provides first evidence showing that the cardiac glycosides induce autophagy in human NSCLC cells through regulation of both mTOR and ERK1/2 signaling pathways. The autophagy may at least partially account for the growth inhibitory effects of the compounds in human NSCLC cells.
    The international journal of biochemistry & cell biology 06/2012; 44(11):1813-24. · 4.89 Impact Factor
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    ABSTRACT: Although salidroside and salidroside-like compounds are considered as most critical constitutes needed and responsible for multiple therapeutic benefits of Rhodiola rosea L., including anti-aging, direct demonstration regarding the role of salidroside in anti-aging process is still deficient. In this study, we selected the H(2)O(2)-induced premature senescence model in human fetal lung diploid fibroblasts to investigate the protection of salidroside against aging in vitro and associated molecular mechanisms. We found that salidroside considerably reversed senescence-like phenotypes in the oxidant challenged model, including alterations of morphology, cell cycle, SA-β-gal staining, DNA damage, as well as related molecules expression such as p53, p21 and p16. The protection occurred in a dose-dependent manner, with 5μM offering best efficacy. The proposed antioxidant property of the compound was confirmed in this cellular system, and thus at least partially accounted for the protection of the compound against premature senescence. Similar protection of salidroside against replicative senescence was observed as well. Interestingly, the regulation of senescence-related molecules by salidroside involved ROS-irrelevant mechanisms in both models. This finding presents salidroside as an attractive agent with potential to retard aging and attenuate age-related diseases in humans.
    Mechanisms of ageing and development 10/2010; 131(11-12):723-31. · 4.18 Impact Factor
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    ABSTRACT: To investigate the protective effects of putative AGEs (advanced glycation endproducts) inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. A group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein (GFAP) and neurotrophin-3 (NT-3) in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined. D-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 (IL-2) production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment. Salidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.
    Biomedical and Environmental Sciences 04/2010; 23(2):161-6. · 1.15 Impact Factor
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    ABSTRACT: Lidamycin, an enediyne antibiotic, leads to apoptosis and mitotic cell death of human tumor cells at high and low concentrations. The reason why tumor cells have distinct responses to lidamycin remains elusive. This study was to elucidate if cellular prosurvival molecules are involved in these responses. Cleavage of chromatin and DNA was observed by chromatin condensation and agarose gel electrophoresis. Accumulation of rhodamine 123 in lidamycin-treated cells was assayed by flow cytometry. Cell multinucleation was detected by staining with Hoechst 33342. Western blot and senescence-associated beta-galactosidase (SA-beta-gal) staining were used to analyze protein expression and senescence-like phenotype, respectively. SIRT1 deacetylase remained unchanged in 0.5 nmol/L lidamycin whereas cleavage occurred when apoptosis was induced by lidamycin. Increased FOXO3a, SOD-1 and SOD-2 expression and transient phosphorylation of ERK were detected after exposure of human hepatoma BEL-7402 cells to 0.5 nmol/L lidamycin. High expressions of SIRT1 and Akt were found in colon carcinoma HCT116 p53 knock-out cells exposed to lidamycin. Degradation of PARP and p53 by lidamycin as a substitute for SIRT1 and Akt was confirmed with caspase inhibitor Q-VD-OPh and proteasome inhibitor MG132. Resistance to lidamycin-induced DNA cleavage was observed in breast cancer doxorubicin-resistant MCF-7 cells. This was not induced by P-glycoprotein as no accumulation of rhodamine 123 was detected in the resistant cells following exposure to lidamycin. In contrast to sensitive MCF-7 cells, a lower multinucleation rate for the resistant cells was measured following exposure to equal concentrations of lidamycin. Cellular prosurvival molecules, such as SIRT1, Akt, SOD-1, SOD-2 and other unknown factors can influence the action of lidamycin on human tumor cells.
    Biomedical and Environmental Sciences 07/2009; 22(3):244-52. · 1.15 Impact Factor
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    ABSTRACT: The mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in both human breast cancer MCF-7 and MCF-7 doxorubicin-resistant cells was studied. MTT assay was used to detect growth-inhibitory effect on the cells. Protein expression was detected by Western blotting. Chromatin condensation was detected by a fluorescent microscope after Hoechst 33342 staining. Cell cycle distribution was analyzed with flow cytometry. Apoptotic cells were detected with Annexin V staining. Nicotinamide (NAM) and Sirtinol, two SIRT1 deacetylase inhibitors, exhibited the similar growth-inhibitory effects on MCF-7/DOX cells and MCF-7 cells, but no potentiation of DOX activities. The arrest at G2/M phase was detected by flow cytometry in both MCF-7 and MCF-7/DOX cells after NAM treatment. Activation of caspase pathway in MCF-7 cells, such as the cleavages of PARP, caspase-6, -7, -9, were observed after exposure to NAM 50 mmol x L(-1), accompanied by the occurrence of chromatin condensation and Annexin V positive cells. However, the cleavages of PARP, caspase-6 and -7 in MCF-7/DOX cells delayed after exposure to NAM for 24 h and obviously increased at 48 h with appearance of chromatin condensation and Annexin V positive cells. SIRT1 deacetylase inhibitors show no cross resistance to MCF-7 drug-resistant cells, and the similar growth-inhibitory actions of them to MCF-7 sensitive and drug-resistant cells by which it is mediated by activation of apoptotic caspase pathway.
    Yao xue xue bao = Acta pharmaceutica Sinica 11/2008; 43(10):1003-10.
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    ABSTRACT: To study whether Lycium barbarum glycopeptide 3 (LBGP3) affects T cell apoptosis in aged mice. LBGP3 was purified with DEAE cellulose and Sephadex columns. Apoptotic "sub-G1 peak" was detected by flow cytometry and DNA ladder was resolved by agarose gel electrophoresis. Levels of IFN-gamma and IL-10 were measured with specific kits and mRNA expression was detected by RT-PCR. Apoptosis-related proteins of FLIP, FasL, and Bcl-2 were determined by Western blotting. LBGP3 was purified from Fructus Lycii water extracts and identified as a 41 kD glycopeptide. Treatment with 200 microg/mL LBGP3 increased the apoptotic rate of T cells from aged mice and showed a similar DNA ladder pattern to that in young T cells. The reversal of apoptotic resistance was involved in down-regulating the expression of Bcl-2 and FLIP, and up-regulating the expression of FasL. Lycium barbarum glycopeptide 3 reverses apoptotic resistance of aged T cells by modulating the expression of apoptosis-related molecules.
    Biomedical and Environmental Sciences 07/2008; 21(3):212-7. · 1.15 Impact Factor
  • Biomedical and Environmental Sciences - BIOMED ENVIRON SCI. 01/2008; 21(3):212-217.
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    ABSTRACT: Although enediyne antibiotic lidamycin ( LDM) is a potent inducer of apoptosis, the underlying mechanisms of its apoptotic functions remain to be explored. Here, we aim to elucidate its possible mechanisms in mitochondria initiated apoptotic pathway involved in human BEL-7402 and MCF-7 cells. Cytochrome c released from mitchondria to cytosol fraction was detected by Western blotting. p53 and Bax, Bcl-2 expressions were detected by Western blotting and RT-PCR. MTT assay was used to detect cytotoxicity of LDM with or without caspase inhibitor z-VAD-fmk. After the BEL-7402 cells were exposed to 0. 1 micromol x L(-1) LDM within 6 h, the increase of cytochrome c in the cytosol and decrease in the mitochondria were observed when compared with untreated cells. The expression of Bax, an important proapoptotic member of the Bcl-2 family, increased gradually in the BEL-7402 cells after exposure to LDM of 0. 1 micromol x L (-1) for 2, 6, and 9 h, separately, while Bcl-2 increased at 2 and 6 h, and decreased at 9 h after LDM treatment. Enhanced protein expressions were parallel with respective increased mRNA level for Bax only, but not p53. Caspase inhibitor may inhibit partially the killing effects induced by LDM. Therefore we conclude that the rapid activation of mitochondrial pathway induced by LDM in tumor cells might contribute to its highly potent cytotoxicities.
    Yao xue xue bao = Acta pharmaceutica Sinica 03/2007; 42(2):132-8.
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    ABSTRACT: To investigate the role of D-galactose, especially in the structural and functional changes of the immune system in aging. Serum levels of advanced glycation end-products (AGE) were determined by ELISA method. Ultra-structures of thymus and spleen were detected by transmission electron microscopy. MTT method was used to determine the lymphocyte proliferation. IL-2 activity was determined by bioassay. Northern blot was used to detect the IL-2 mRNA levels. Serum AGE levels of D-galactose- (P < 0.01) and AGE-treated (P < 0.05) mice (n = 8) were increased significantly. The ultra-structures of thymus and spleen in D-galactose- and AGE-treated mice showed regressive changes similar to those in the aged control group. The lymphocyte mitogenesis and IL-2 activity of spleen were also decreased significantly (P < 0.01, n = 8). The change of IL-2 activity shown by Northern blot resulted from the change of mRNA expression. The AGE plus aminoguanidine group, however, showed no significant change in these parameters in comparison with the young control group (P < 0.01 or P < 0.05, n = 8). D-galactose and AGE lead to a mimic regression change of aging in the immune system in vivo.
    Biomedical and Environmental Sciences 12/2006; 19(6):432-8. · 1.15 Impact Factor
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    ABSTRACT: A new antibiotic, S632A3, was isolated from a cultured broth of Streptomyces hygroscopicus S632. It was purified by column chromatography on silica gel, Sephadex LH-20 and HPLC. Structural studies by analysis of 1H NMR and 13C NMR, MS, UV and IR spectra in comparison with those of S632A2 clarified that S632A3 is an isomer of 9-methylstreptimidone. In addition, this antibiotic showed potent biological activity including differentiation induction effects on HL-60 cell and antitumour activity in vivo.
    Journal of Asian Natural Products Research 01/2006; 8(1-2):55-60. · 0.95 Impact Factor
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    ABSTRACT: The insulin/insulin-like growth factor 1 (IGF-1) signaling pathway is evolutionary conserved in diverse species including C.elegans, saccharomyces cerevisiae, Drosophila melanogaster, rodents and humans, which is involved in many interrelated functions that are necessary for metabolism, growth and reproduction. Interestingly, more and more research has revealed that insulin/IGF-1 signaling pathway plays a pivotal role in the regulation of longevity. Generally, disruption of the power of this pathway will extend longevity in species ranging from C.elegans to humans. The role of insulin/IGF-1 in longevity is probably related to stress resistance. Although the underlying mechanisms of longevity are not fully understood, the Insulin/IGF-1 signaling pathway has attracted substantial attention and it will be a novel target to prevent or postpone age-related diseases and extend life span. In this review, we mainly focus on the similar constitution and role of insulin/IGF-1 signaling pathway in C.elegans, saccharomyces cerevisiae, rodents and humans.
    World Journal of Gastroenterology 05/2005; 11(13):1891-5. · 2.55 Impact Factor
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    Jian-Ming Jiang, Zhen Wang, Dian-Dong Li
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    ABSTRACT: To investigate whether two kinds of in vitro prepared advanced glycation end products (AGEs), Glu-BSA and Gal-BSA, could change oxidation stress and anti-oxidation abilities in astrocytes, and thus might contribute to brain injury. Changes of GSH, MDA, SOD, MAO-B, nitric oxide were measured after AGEs treatment. Both 0.1 g/L Glu-BSA and Gal-BSA could slightly decrease GSH level, while 1 g/L of them significantly decreased GSH level by 35% and 43% respectively. The MDA levels of both 1 g/L AGEs treated groups (306 +/- 13 and 346 +/- 22) were higher than that of the normal group (189 +/- 18), which could be inhibited by free radical scavenger NAC. The SOD activities of both 1 g/L AGEs treated groups (67.0 +/- 5.2 and 74.0 +/- 11.0) were lower than that of the normal group (85.2 +/- 8.0). Both 0.1 g/L AGEs could slightly increase the activity of MAO-B, while 1 g/L of them could increase MAO-B activity by 1.5 and 1.7 folds respectively. Both AGEs stimulation could produce NO level by 1.7 and 2 folds respectively. Enhanced levels of astrocytic oxidation stress and decrease of antioxidation abilities may contribute to, at least partially, the detrimental effects of AGEs in neuronal disorders and aging brain.
    Biomedical and Environmental Sciences 04/2004; 17(1):79-86. · 1.15 Impact Factor
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    ABSTRACT: To investigate the inhibiting effects and mechanism of achyranthes bidentata polysaccharide (ABP) and lycium barbarum polysaccharide (LBP) on nonenzyme glycation in D-galactose induced mouse aging model. Serum AGE levels were determined by AGE-ELISA, MTT method was used to determine lymphocyte proliferation, IL-2 activity was determined by a bioassay method. Spontaneous motor activity was used to detect mouse's neuromuscular movement, latency of step-through method was used to examine learning and memory abilities of mouse, colormetric assay was used to determine hydroxyproline concentration in mouse skin, pyrogallol autoxidation method was used to determine superoxide dismutase (SOD) activity of erythrocytes. Decreased levels of serum AGE, hydroxyproline concentration in mouse skin and spontaneous motor activity in D-galactose mouse aging model were detected after treated with ABP or LBP, while lymphocyte proliferation and IL-2 activity, learning and memory abilities, SOD activity of erythrocytes, were enhanced. ABP and LBP could inhibit nonenzyme glycation in D-galactose induced mouse aging model in vivo and ABP has a better inhibiting effect than LBP.
    Biomedical and Environmental Sciences 10/2003; 16(3):267-75. · 1.15 Impact Factor
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    ABSTRACT: To investigate whether two kinds of in vitro prepared advanced glycation end products (AGE), Glu-BSA and Gal-BSA, could induce proinflammatory mediators IL-1beta and TNF-alpha, as well as oxidative stress and nitric oxide (NO), in astrocytes, thus contributing to brain injury. Radioimmunoassay and RT-PCR technique were used to detect two cytokines' level and existence of receptor for AGE (RAGE). DTNB reaction was used to measure reduced glutathione (GSH) level. NO content was assayed using Griess reagent provided by Promega. Enhanced protein levels of both cytokines in supernatants and cell lysates of astroglia cultures were detected after treated with AGE-BSA 1 g/L, especially Gal-BSA, for 72 h. The increases were also in a concentration-dependent manner. Changes in protein levels might be attributed to changes in transcriptional levels documented by semi-quantitative RT-PCR. Both AGE-BSA could also reduce astrocytic GSH and induce NO release. RAGE was detected in astrocytes. Enhanced levels of astrocytic proinflammatory mediators IL-1beta and TNF-alpha, and oxidative stress caused by AGE might contribute to, at least partially, the detrimental effects of AGE in neuronal disorders and aging brain.
    Acta Pharmacologica Sinica 12/2002; 23(11):974-80. · 2.35 Impact Factor

Publication Stats

112 Citations
25.89 Total Impact Points

Institutions

  • 2010
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 2003–2009
    • Peking Union Medical College Hospital
      Peping, Beijing, China