[Correlation between antimetastatic action of Ajuga decumbens and expression of MMPs and TIMPs].

OBJECTIVE: To investigate the anticancer and anti-metastatic effect of Ajuga decumbens extraction (HBG) on breast cancer and to clarify the effect of HBG on MMPs and TIMPs. METHOD: The antitumor and antimetastic effect of HBG was determined using orthotopic 4T1 breast cancer mouse model. Western blot analysis was employed to detect the expression of associated proteins in breast cancer metastasis. RESULT: Administration with 50-200 mg x kg(-1) doses of HBG significantly reduced the tumor weight, tumor volume and numbers of lung tumor nodules in a dose-dependent manner. Tumor metastasis correlated proteins were altered following HBG treatment, MMP-2 and MMP-9 were down-regulated while TIMP-1 and TIMP-2 were up-regulated. CONCLUSION: HBG showed anticancer and antimetastatic effect towards breast cancer through regulating the expression of MMPs and TIMPs. These data sustain our contention that HBG might be used as a potential therapeutic agent.

[Function of MMP/TIMP on airway remodeling of bronchial asthma and treating effects of Zhichuan capsule].

OBJECTIVE: To explore the mechanism of the bronchial asthma and to study the treating effects of Zhichuan Capsule on the airway remodeling of asthmatic model rats. METHODS: The rat model was established by being sensitized and activated with different density of ovalbumin through prolonged and repeated exposure for 8 weeks. The rats were randomly divided into model group, Zhichuan Capsule treated group, dexameson treated group, and Zhichuan Capsule and dexameson treated group. Another group of normal rats were taken as control. General histological changes were observed by hematoxylin and eosin stained sections. Being standardized by internal perimeter (Pi), the wall thickness (d), internal area (Ai), outer area (Ao) and wall area (WA) of the airway were quantified by computer-assisted image analysis system. The express of MMP-9, TIMP-1, Col I, Col III and ColV in the airway were examined by immunocytochemical methods. During the course of airway remodeling, the dynamic changes of model rats were observed at different time points (2, 4, 6 and 8 weeks after the activating). Statistical comparison was performed by ANOVA followed by Fisher LSD test. RESULTS: (1) Histologic examination showed eosinophil infiltration within the airway walls, epithelial damage, excessive mucus in the lumen and edema in the submucosa of the airways in model rats, and that the collagen deposition increased accompanied by increasing of TIMP-1. In the model rats, MMP-9 increased at the time point of 2 weeks, but it decreased in the late stage (8 weeks after activating) of airway remodeling. And the level of TIMP-1 was far higher than MMP-9 at the time point of 8 weeks. (2) Zhichuan Capsule could down-regulate the level of TIMP-1 in the airway wall, as well as the thickness of airway wall and the collagen deposition. And there were progressing effects when it was used together with dexameson. CONCLUSION: (1) The early increase of MMP-9 is a key point to start remodeling; and the increase of TIMP-1 in the late stage, which inhibits collagenase activity, may play an important role in developing airway fibrosis. Imbalance between MMP-9 and TIMP-1 is a marker of airway remodeling. (2) Zhichuan Capsule can decrease the deposition of collagen and suppress the airway remodeling by inhibiting the TIMP-1 expression.

Effects of a vegetable extract from Lupinus albus (LU105) on the production of matrix metalloproteinases (MMP1, MMP2, MMP9) and tissue inhibitor of metalloproteinases (TIMP1, TIMP2) by human gingival fibroblasts in culture.

This study examined the effects of a vegetable extract from Lupinus albus (LU105) on MMPs and TIMPs secreted by human gingival fibroblasts in culture. LU105 was extracted from seeds of L. albus and is freely soluble in water. Gelatin zymography showed that control human gingival fibroblasts maintained in culture for 48 h express pro-MMP2 (progelatinase A) in the culture medium while the active form of MMP2 (gelatinase A), the active form of MMP9 (gelatinase B), and pro-MMP9 (progelatinase B) are not detected. Fibroblasts derived from inflamed gingiva expressed in the culture medium increased amounts of pro-MMP2 (progelatinase A) compared with controls and significant amounts of pro-MMP9 (progelatinase B). LU105 diminished the expression by gingival fibroblasts derived from inflamed tissue of both pro-MMP2 and pro-MMP9. Furthermore LU105 did not modify the amount of TIMP2 expressed in culture by controls or by gingival fibroblasts derived from inflamed tissue. TIMP1 and MMP1 significantly decreased when LU105 was added in the culture media of gingival fibroblasts derived from inflamed tissue compared with control fibroblasts. Thus LU105 seems to offer an opportunity to restore a correct balance between MMP2, MMP9, MMP1, and their natural inhibitors, i.e., TIMP1 and TIMP2 in human inflamed gingiva.