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Aim: To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats., Methods: Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy., Results: Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers., Conclusion: Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease., ((c) 2008 S. Karger AG, Basel.)

Among the eight Calophyllum species found on the American continent, Calophyllum brasiliense is the most widely distributed. Chemical analysis of this species has shown the presence of xanthones with cancer chemopreventive properties and antifungal activity. Recently, three new coumarins with antineoplastic properties have been found. In this study, we have evaluated the biological effects of the antiproliferative activity of coumarins isolated from C. brasiliense on the survival, cell cycle and apoptosis of cells in-vitro and their antitumour effects in mice. The cytological study showed that coumarins from C. brasiliense reduce the survival of BMK cells (baby mouse kidney cells) by inducing apoptosis and, to a lesser degree, necrosis. The cell cycle was arrested in S-phase and the division of BMK cells was inhibited. Coumarins had caused a reduction of experimental tumours in 83% of animals by the end of the treatment. Therefore, coumarins have the potential to be used alone or in combination with other antineoplastic drugs, and they might increase the effectiveness of other treatments for cancer.

Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment with the aim of modifying the clinical course of this disease is evident. The aim of this work is to determine whether genistein, which has been shown to modulate the physiology and pathophysiology of liver, is able to decrease experimental liver fibrosis and cholestasis. In male Wistar rats, the common bile duct was ligated. Administration of genistein (5 microg rat-1, day-1, p.o.) began four weeks after biliary obstruction and continued for a further four weeks. The liver was used for histological and ultrastructural analysis and for collagen quantification (hydroxyproline content). The degradation of Matrigel(R) and collagen type I was determined in homogenized liver. Bilirubins and enzyme activities were measured in serum. Genistein was able to improve normal liver histology, ultrastructure, collagen content, and biochemical markers of liver damage. It also increased Matrigel(R) and collagen type I degradation. In summary, the present report shows that genistein inhibits the fibrosis and cholestasis induced by prolonged biliary obstruction in the rat. Genistein has therapeutic potential against liver fibrosis.

Background: Calophyllum (Clusiaceae) plants have been used as traditional medicine for rheumatism, vein problems, hemorrhoids, and gastric ulcers. The traditional uses of this genus prompted us to investigate six Malaysian Calophyllum species which are Calophyllum inophyllum, Calophyllum soulattri, Calophyllum lowii, Calophyllum teysmannii, Calophyllum benjaminum and Calophyllum javanicum for their anti-inflammatory properties. Materials and Methods: The stem bark of six plants was extracted with n-hexane (Hex), ethyl acetate (EA), and methanol (MeOH). The activities of the extracts were evaluated by determining the inhibition of nitric oxide (NO) production by lipopolysaccharide-induced RAW 264.7 cells, as well as protein denaturation. Results and Discussion: The C. lowii extracts showed the most significant activities against NO production with IC50values of <40 μg/mL. For the protein denaturation test, C. teysmannii extracts showed the strongest effect with IC50values of <100 μg/mL. The results indicated that C. lowii and C. teysmannii are effective in both assays. Besides, the Hex extracts of these Calophyllum plants possess stronger activities than the EA and MeOH extracts. The anti-inflammatory properties are contributed by the secondary metabolites present in the crude extracts, specifically flavonoid, triterpenes, and xanthones. Conclusion: These results confirm the potential of Calophyllum plants to serve as lead agents in preventing inflammation. Abbreviations used: NO: Nitric oxide; spp.: Species; Hex: Hexane; EA: Ethyl acetate; MeOH: Methanol. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to investigate the relationship between urokinase-type plasminogen activator (uPA) and mitogen-activated protein kinase 38 (p38MAPK), and preliminarily analyze their relationship with clinical characteristics of esophageal cancer. Materials and methods: Immunohistochemistry and Western blot were used to detect the expressions of uPA and p38MAPK in patients with esophageal cancer. The relationship between them and clinicopathological features was analyzed by chi-squared test and Spearman correlation. Prognosis was performed using Kaplan–Meier and Cox proportional hazard models analysis. Results: The expressions of uPA and p38MAPK proteins were significantly higher in esophageal squamous cell carcinoma or adenocarcinoma than in normal esophageal mucosa tissue (both P<0.0001). The expression of uPA was significantly correlated with the depth of invasion of esophageal cancer (P=0.0067), tumor size (P=0.0364), and pathological stage (P<0.0001); p38MAPK expression vs esophageal cancer tissue type (P=0.0043), esophageal cancer infiltration depth (P=0.0097), tumor size (P=0.0015), and pathological stage (P<0.0001). Both were not significantly associated with lymph node staging, gender, age, and esophageal cancer histological type. There was a positive correlation between uPA and p38MAPK expressions (r=0.7301, P=0.0104). Kaplan–Meier analysis showed that the overall survival time of patients with positive expression of uPA or p38MAPK protein was significantly shorter, and the time of recurrence or metastasis of esophageal cancer was significantly earlier in patients with uPA-positive expression. Multivariate analysis of Cox model showed that uPA, p38MAPK, and pathological staging were independent factors influencing survival. Conclusion: The expressions of uPA and p38MAPK may play an important role in the progression of esophageal cancer, and there is a close relationship between the two proteins, which may be one of the prognostic indicators. [ABSTRACT FROM AUTHOR]

The Calophyllum genus is well-known for its antimicrobial and cytotoxic activities, and therefore, we analyzed these biological activities for resins of Calophyllum antillanum and Calophyllum inophyllum growing in Cuba. C. antillanum resins showed a potent activity against Plasmodium falciparum (IC50  = 0.3 ± 0.1 µg/mL), while its cytotoxicity against MRC-5 cells was much lower (IC50  = 21.6 ± 1.1 µg/mL). In contrary, the resin of C. inophyllum showed an unspecific activity. The presence of apetalic acid, isoapetalic acid, calolongic acid, pinetoric acid I, pinetoric acid II, isocalolongic acid, pinetoric acid III, and isopinetoric acid III in C. antillanum resins was also confirmed. These results demonstrated for the first time the potential activity of C. antillanum resins against P. falciparum. [ABSTRACT FROM AUTHOR]