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OBJECTIVE： To study the effects of Capparis spinosa total alkaloid on Notch pathways related protein Notch2， Delta-like 3 （DLL3）， Jagged1 and Notch intracellular domain 1 （NICD1） in mice with systemic sclerosis （SSc）. METHODS： BALB/c mice were randomly divided into blank control group， model group， positive control group （penicillamine 125 mg/kg）， C. spinosa total alkaloid low-dose， medium-dose and high-dose groups （225， 450， 900 mg/kg）， with 16 mice in each group. Except for blank control group， other groups were given bleomycin subcutaneously for 4 weeks to induce SSc model. C. spinosa total alkaloid groups were given relevant dose of C. spinosa total alkaloid cream for external use. Positive control group was given relevant dose of penicillamine intragastrically. Blank control group and model groups were given cream matrix without drug， once a day， for consecutive 8 weeks. 4 h after last administration， the skin of the administration area of each group of mice was collected. mRNA expression of Notch2 and NICD1 was detected by real-time PCR； the content of DLL3 was measured by ELISA； the protein expression of Jagged1 in skin tissue was detected by immunohistochemstry. RESULTS： Compared with blank control group， mRNA expression of Notch2 and NICD1， DLL3 content， protein expression of Jagged1 were markedly increased， with statistical significance （P＜0.01）. Compared with model group， mRNA expression of NICD1， DLL3 content and protein expression of Jagged1 were decreased significantly in C. spinosa total alkaloid medium-dose and high-dose groups， positive control group， mRNA expression of Notch2 in skin tissue were decreased significantly in C. spinosa total alkaloid high-dose group and positive control group， with statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： C. spinosa total alkaloid can inhibit the abnormal expression of Notch2， NICD1， DLL3 and Jagged1 in skin tissue of SSc model mice， and inhibit over activation of Notch pathway in SSc model mice.
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Objective To evaluate the effects of capparis spinosa total alkaloid on transforming growth factor-β( TGF-β)/Smad4 signalling pathways in systemic sclerosis (SSc). Methods A total of 90 BALB/c mice were randomly divided into normal control group, model control group, penicillamine ( 125 mg·kg-1) group and Capparis spinosa total alkaloid low (225 mg·kg-1),medium (450 mg·kg-1) and high ( 900 mg·kg-1) dose group. Except for the normal control group,SSc mouse model was established by daily subcutaneous injection of bleomycin in the back of the mice.After the establishment of the model,Capparis spinosa total alkaloid emulsifiable paste was externally applied to Capparis spinosa total alkaloid group,ground substance was externally applied to the mice in normal control group and model control groups, and penicillamine was intragastrically administrated in the penicillamine group for 60 days,once daily.After the treatment,The expression of TGF-β1in skin tissue was detected by Western-blotting and the levels of actin / in receptor-like kinase / Smad4, nuclear factor-κB in skin tissue were measured by ELISA. Results The expression of TGF-β1was significantly decreased after administration of 225,450 and 900 mg·kg-1capparis spinosa total alkaloid, and the levels of ALK1 and Smad4 were significantly decreased after administration of 900 mg·kg-1capparis spinosa total alkaloid as compared with model control group (P<0.05 or P<0.01),but the content of NF-κB was not influenced (P>0.05). Conclusion Capparis spinosa total alkaloid can accommodate abnormal expression of TGF-β1/Smad4 signalling pathways in SSc.
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Objective To observe the effects of Capparis spinosa total alkaloid on vascular endothelial growth factor (VEGF),endothelin-1(ET-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in systemic sclerosis (SSc) mouse model and explore the therapeutic mechanism of Capparis spinosa total alkaloid for the treatment of SSc. Methods A total of 90 BALB/c mice were randomly divided into blank control group,model control group,penicillamine (125 mg·kg-1) group and Capparis spinosa total alkaloid low(225 mg·kg-1),medium(450 mg·kg-1) and high(900 mg·kg-1) dose group. Except for the blank control group,SSc mouse model was established by daily subcutaneous injection of bleomycin in the back of the mice.After establishing model successfully,Capparis spinosa total alkaloid emulsifiable paste was externally applied with Capparis spinosa total alkaloid group,ground substance was externally applied to the mice in blank control group and model control groups,penicillamine was intragastrically administrated in the penicillamine group for 60 days,once daily.After the treatment,the content of VEGF in skin tissue and ET-1,sVCAM-1 in serum were measured by ELISA. Results The levels of VEGF and ET-1 were significantly decreased in Capparis spinosa total alkaloid high dose group as compared with model control group(P<0.05, P<0.01),but the content of sVCAM-1 wasn't influenced(P>0.05). Conclusion Capparis spinosa total alkaloid is effective in adjusting abnormal expression of VEGF and ET-1 in SSc mice.
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Objective To investigate the effects of capparis spinosa total alkaloid on the pathological changes and the type Ⅲ collagen(COL?Ⅲ)expression in systemic sclerosis(SSc)mice. Methods Mice models with SSc were established by repeated local injection of bleomycin in BALB/c mice back. After administration of capparis spinosa total alkaloid ,the pathological changes of skin and lung tissue were observed ,and the COL?Ⅲ expression was detected by ELISA. Results Compared with the model group,the inflammation and fibrosis of skin and lung tissue were improved,and the level of COL?Ⅲ was markedly reduced by treatment of high dose capparis spinosa total alkaloid(P<0.05). Conclusion Cap?paris spinosa total alkaloid is effective in treating fibrosis of SSc.
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Objective To investigate the effects of capparis spinosa total alkaloid on type collagen (ColⅣ - ),Ⅳmatrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in bleomycin-induced systemic sclerosis (SSc) mice; To explore the effective mechanism of capparis spinosa total alkaloid on fibrosis of SSc. Methods Totally 90 BALB/c mice were randomly divided into control group, model group, penicillamine group and capparis spinosa total alkaloid low-, medium- and high-dose group. Mice models with SSc were established by repeated local injections of bleomycin in mice back, except for the control group. Mice in medication groups received external application with capparis spinosa total alkaloid cream;mice in penicillamine group were given penicillamine for gavage; mice in the control and model group received external application without substance, one time a day, for 60 days. The contents of MMP-9, TIMP-1 and PAI-1 in serum and Col- in skin tissue were dⅣ etected respectively by ELISA after the last medication. Results Compared with the model group, the levels of MMP-9 and ratio of MMP-9/TIMP-1 markedly increased and the levels of Col-Ⅳand TIMP-1 markedly decreased in medium and high- dose of capparis spinosa total alkaloid group (P0.05). Conclusion Capparis spinosa total alkaloid is effective in treating fibrosis of SSc by adjusting imbalance of MMP-9/TIMP-1 and decreasing expression of Col-Ⅳ.
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Objective To investigate the effects of moldavica total flavone on vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1), nitric oxide (NO) and endothelin-1 (ET-1) in ovalbumin-induced bronchial asthmatic rats, and explore its mechanism. Methods A total of 60 SD rats was randomly divided into control group, model group, dexamethasone (1 mg/kg) group and moldavica total flavone low (90 mg/kg), medium (180 mg/kg) and high (360 mg/kg) dose group. Rats asthma model was established by ovalbumin challenge methods except the control group. After modeling, rats in control and model groups were intragastrically given distilled water, rats in medicine groups were intragastrically given moldavica total flavone and dexamethasone for 30 d. VEGF in lung tissue and ICAM-1 in bronchoalveolar lavage fluid (BALF) were detected respectively by ELISA. The content of ET-1 and NO in BALF were analyzed with radioimmunity method and nitric acid reductase method. Results The VEGF in lung tissue and ICAM-1, NO and ET-1 in BALF were decreased by moldavica total flavone at 180 and 360 mg/kg (P<0.05, P<0.01) in ovalbumin-induced bronchial asthmatic rats. Conclusion Moldavica total flavone is effective in adjusting abnormal increase of VEGF, ICAM-1, ET-1 and NO of bronchial asthma rats.
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Objective To investigate the effect of moldavica total flavone on pulmonary function and collagen type Ⅲ in lung tissue of ovalbumin-induced bronchial asthmatic rats. Methods A total of 60 SD rats were randomly divided into control group, model group, dexamethasone group, and moldavica total flavone low, medium and high dose group. Rat asthma model was established by ovalbumin challenge methods except the control group. The control and model group were intragastrically given distilled water, medicine groups were intragastrically given moldavica total flavone and dexamethasone for 30 d, once per day. After the last administration, the pulmonary function and airway responsiveness including breathing frequency (F), minute ventilation (MVb), peak inspiratory flow (PIFb), peak expiratory flow (PEFb) and enhanced pause (Penh) were measured by using non-invasive measurement system (Penh system, Buxco, USA). The collagen type Ⅲ in lung tissue were detected by ELISA. Results The moldavica total flavone at 180 and 360 mg/kg decreased F and Penh (P<0.05, P<0.01), increased MVb, PIFb and PEFb (P<0.05), and decreased collagen type Ⅲ in lung tissue (P<0.05, P<0.01). Conclusion Moldavica total flavone can relieve the airway hyperresponsiveness and remodeling, improve respiratory function of ovalbumin-induced bronchial asthmatic rats.