1.Research on CXCL12/CXCR4 biological axis and idiopathic pulmonary fibrosis
Hongxia CUI ; Yizhong FENG ; Zhenlun GU ; Xiaogang JIANG ; Ciyi GUO
Chinese Pharmacological Bulletin 2010;26(3):298-301
Idiopathic pulmonary fibrosis(IPF), with unknown pathogeny, is an interstitial lung disease.The pathological features are diffuse epithelial-cell lesion, fibroblast proliferation, myofibroblast differentiation and excessive extracellular matrix deposition.CXCR4 is the predominant chemokine receptor on fibrocytes;CXCL12 is the only ligand of CXCR4.A large number of studies have shown that CXCL12/CXCR4 biological axis plays an important role in the pathogenesis of idiopathic pulmonary fibrosis.Under the regulation of hypoxia, HIF-1α and PI3K-Akt-mTOR path, CXCL12/CXCR4 biological axis promotes lung fibroblast proliferation, myofibroblast differentiation and extracellular matrix deposition, resulting in development and progression of IPF.
2.The inhibitory effect of oridonin on human pancreas adenocarcinoma SW1990 cells
Fang SONG ; Yizhong FENG ; Xiaogang JIANG ; Zhenlun GU ; Ciyi GUO
Chinese Pharmacological Bulletin 2010;26(2):240-243
Aim To study the inhibitory effects and its mechanisms of oridonin on human pancreas adenocarcinoma SW1990 cells.Methods Cell growth inhibition mediated by oridonin on SW1990cells was measured by MTT assay.The morphological changes were observed by Hoechst33258 fluorochrome staining and electron microscope.Cell cycle and apoptosis rate were analyzed by flow cytometry. The molecular mechanisms involved in the effects of oridonin on SW1990 cells were studied by RT-PCR.Results The growth of humen pancreas adenocarcinoma SW1990 cells was significantly inhibited by oridonin.Apoptosis morphological changes about chromatic agglutination and nuclear condensation were detected by Hoechst 33258 fluorochrome staining and electron microscope in oridonin treated SW1990 cells."Sub-G_1" phase peak and G_2/M growth arrest werer found with flow cytometry.The upregulating mRNA expression of p21 and downregulating mRNA expression of survivin were detected by RT-PCR.Conclusion The inhibitory effect of oridonin on human pancreas adenocarcinoma SW1990 cells through induced apoptosis and G_2/M growth arrest and the mechanisms may be through surviving-p21 co-regluation pathway.
3.Research progress in osteopontin and pulmonary fibrosis
Haibiao HE ; Zhenlun GU ; Xiaogang JIANG ; Wenxuan ZHOU ; Ciyi GUO
Chinese Pharmacological Bulletin 2010;26(2):151-155
Osteopontin (OPN) is a secreted O-glycosylated phosphoprotein that exists in a variety of tissues and body fluids, with a variety of biological activity. Integrin α_vβ_3 is the main receptor. OPN mainly involves in cell proliferation, differentiation, migration and adhesion. The study of OPN at home and abroad mainly focuses on the bone resorption, angiogenesis, atherosclerosis, digestive system, urinary system, wound healing, skin fibrosis, liver fibrosis, kidney fibrosis, etc.But reports about OPN in pulmonary fibrosis are much less, now the relationships between OPN and pulmonary fibrosis are reviewed.
4.Prevention of Bleomycin-induced Pulmonary Fibrosis in Mice by the Combination of Hirsutella sinensis and Panax notoginseng Extracts
Yizhong FENG ; Yongsheng ZHANG ; Zhifei CAO ; Zhenlun GU ; Qingyao YANG ; Xiaotong YANG ; Wenhsien CHOU ; Chiyi KWOK
Chinese Herbal Medicines 2010;02(2):118-124
Objective Hirsutella sinensis (HS) is the anmorph of Ophiocordyceps sinensis (Cordyceps sinensis). O.sinensis and Panax notoginseng are two popular Chinese herbs, commonly used in traditional Chinese prescriptions for the treatment of various diseases. A combination of HS extract with P. notoginseng saponin (PNS) extract demonstrated more prominent lung-protective activity than the two herbs individually used in our preliminary studies. This study further investigated the action of their combination (HSPNS) on anti pulmonary fibrosis using a Bleomycin (BLM)induced mouse model. Methods BLM-treated Kunming mice was given HSPNS daily for 7, 14 or 28 d via ig administration. After treatment, following parameters were monitored using proper methods, respectively. Lung index, serum and lung malondialdehyde (MDA) and hydroxyproline (HYP) contents, lung superoxide dismutase (SOD) activity, transforming growth factor β1 (TGF-β1), and expression levels of collagen Ⅰ (Col- Ⅰ) and collagen Ⅲ (Col-Ⅲ). The lung biopsies were also dissected for semiquantitative histological analysis. Results The results indicated that HSPNS significantly reduced lung index, MDA and HYP contents, and expression levels of TGF-β1,Col- Ⅰ, and Col-Ⅲ. The combination also remarkably enhanced SOD activity compared with BLM-induced group.Moreover, the severe pulmonary fibrosis histopathological changes induced by BLM could be attenuated by HSPNS treatment. Conclusion These results suggest that HSPNS could significantly inhibit the progression of pulmonary fibrosis induced by BLM and its inhibitory effect might associate with its ability to scavenge free radicals, decrease TGF-β1 level, and inhibit collagen synthesis.
5.The effects of flavonoids extracts from semen Astragali complanali on the growth of liver cancer and immune function
Cuiping WEI ; Qiyun TANG ; Zhongqin LIANG ; Zhenlun GU
Tumor 2009;(12):1112-1115
Objective:To study the effect of flavonoids extracts from semen Astragali complanati (FAC) on the growth of hepatocellular H22 cells and elucidate its action mechanism. Methods:The mouse model bearing H22 tumor cells was established. The effects of FAC on the growth of xenografted H22 tumor, the immune organ, survival time, phagocytic function of macrophages, and lymphocyte transformation in tumor-bearing mice were observed. Results:The growth of H22 transplanted tumor was significantly inhibited by FAC at high, middle and low doses,compared with normal control group (P<0.05). The tumor-inhibiting ratio in cyclophosphamide (CTX) group was similar with that in FAC high-dose group (P>0.05). FAC markedly elongated the survival time of tumor-bearing mice. The high, middle and low doses of FAC elongated the survival time of tumor-bearing mice by 64.9%, 56.7% and 28.1%, which were significantly different with control group (P<0.01). The high, middle and low doses of FAC greatly increased the thymus index and spleen index of tumor-bearing mice (P<0.05, vs control) and elevated the phagocytic function of macrophages and lymphocyte transformation capability (P<0.01, vs control). The effect of CTX on immune function of tumor-bearing mice was opposite with FAC. The difference between CTX group and control group was significant (P<0.01). Conclusion: FAC inhibits the growth of H22 hepatoma, elongates the survival time, and elevates the non-specific immune function of tumor-bearing mice, indicating that FAC maybe exert its anti-tumor effect via regulating immune function of tumor-bearing mice.
6.Studies on the Analgesic Effect of Polysaccharopeptide and Its Mechanism
Yuanrong LIU ; Zhenlun GU ; Qizhang YIN
Journal of Zhejiang Chinese Medical University 2006;0(06):-
[Objective]The study focus on the analgesic effect of polysaccharopeptide(PSP)and discuss the mechanism of this analgesia. [Methods]A total of 80 rats were divided randomly into high dose of psp,medium dose of psp,low doses of psp,positive control group,negative control group.After intragastric(ig) administration of different(high,medium and low)doses of PSP for 6 days,The tail stimulation-vocalization test was used to observe the analgesic effect of PSP.The IL-2 and IL-2R expression in mediobasal hypothalamus(MBH) was studied immunohistochemically.[Results]After intragastric(ig) administration of PSP for 6 days,the pain threshold was increased significantly and a dose-effect relationship was observed.After PSP administration the IL-2 expression in MBH was increased,while the IL-2R expression in MBH was decreased.[Conclusion]PSP has a definite analgesic effect and its analgesic site is in the MBH.The analgesia might be produced by the binding with the IL-2R in MBH by IL-2 secreted by T cells after PSP was injected into the brain.
7.Effects of ferulic acid on E-selectin expression in activated endothelial cell and leukocyte-endothelial cell adhesion
Xiaolan WANG ; Xiaohui HU ; Mingen Lü ; Zhenlun GU ; Changgeng RUAN
Acta Pharmaceutica Sinica 2005;40(5):410-413
Aim To study the effects of ferulic acid (FA) on E-selectin expression in human umbilical vein endothelial cells (HUVECs) activated by lipopolysaccharide and leukocyte-endothelial cell adhesion. Methods The effects of FA on E-selectin and E-selectin mRNA expression were determined by flow cytometry and reverse transcription polymerase chain reaction. The effect of FA on HL60-HUVEC adhesion was evaluated with the method of staining the cells by Rose Bengal. Results The expression of tively). Conclusion FA can inhibit the expression of E-selectin and E-selectin mRNA and HL60-HUVEC adhesion. This may contribute to its protective effect against ischemia-reperfusion injury.
8.Mechanisms of curcumin protecting endothelial cells against ischemia and reperfusion injury
Wenmin HUA ; Zhongqin LIANG ; Yun FANG ; Zhenlun GU ; Ciyi GUO
Chinese Pharmacological Bulletin 2003;0(08):-
Aim To investigate the mechanisms in protecting HUVEC against ischemia/reperfusion(I/R) injury directed by curcumin.Methods Hypoxia/reoxgenation(H/R) model was established on HUVEC.MTT colorimetric assay was used to observe the injury degree of hypoxia and reoxygenation at the different time.With preconditioning by different concentration of Cur,the survival rate of HUVEC subjected to H/R was assessed by MTT colorimetric assay.Pretreated with Cur(5 ?mol?L-1),the expression of LC3,cathepsin B,cathepsin L,Bax and Bcl-2 were observed by fluorescent staining and Western blot in HUVEC during H/R process.Results Cur(1.25~5 ?mol?L-1) played a protective role during H/R in HUVEC in a dose-dependent manner.During H/R,the expressions of LC3,cathepsin B and the ratio of Bax/Bcl-2 increased,and the nuclear translocation of cathepsin L was induced;when cur was pretreated,LC3 was furtherstrengthened,at the same time,the up-regulation of cathepsin B,the ratio of Bax/Bcl-2 and the nuclei-location of cathepsin L were inhibited partly by Cur.Conclusions Cur can raise the survival rate of HUVEC in the process of H/R.Cur increases the autophagy activity,depresses cathepsins and Bax/Bcl-2 to protect the endothelial cells.
9.New targets of lipid-regulating drugs
Fang SONG ; Meilin XIE ; Zhenlun GU
Chinese Pharmacological Bulletin 2003;0(07):-
Hyperlipidemia is a major risk factor for the generation and development of atherosclerosis and coronary heart disease. The lipid-lowering effects of drugs were mediated by the control of lipid metabolism.Recently some new targets in the process of lipid metabolism were found,they may lead to the development of new drugs.
10.The research progress of cobra venom secretory phospholipase A_2
Yaping YANG ; Zhongqin LIANG ; Zhenlun GU ; Zhenghong QIN
Chinese Pharmacological Bulletin 2003;0(09):-
Cobra venom secretory phospholipase A_2 (sPLA_2) is an important component of cobra venom which has a variety of biological activities. Recent studies are mainly focusing on each pharmacological active component of venom, SPLA_2 is one of them. This review summarized the structure, purification and biological activities of cobra venom sPLA_2 with emphasizing its diverse pharmacological effects and toxicity. In addition, some mechanisms of actions of sPLA_2 and possible applications of sPLA_2 were also discussed.

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