The gastric ulcer protective and healing role of cysteine proteinases from Carica candamarcensis.

Latex from Caricaceae contains proteolytic enzymes localized in the fruit, which are used ethnopharmacologically to treat digestive disorders. Some of these proteins display proliferative properties when probed with mammalian cells, suggesting a role in the reconstruction of wounded tissue. We tested the efficacy of a proteolytic fraction derived from Carica candamarcensis, designated as P1G10 in experimental rodent models, to protect and heal chemically induced gastric ulcers. The protective effect of oral administration of P1G10 fraction was analyzed in indomethacin-treated Wistar animals. The healing effect of P1G10 was studied following sub-serous injection of acetic acid in a Wistar rat model. The results show that P1G10 between 0.1 and 10 mg/kg protect indomethacin but not ethanol-induced gastric ulcers. The maximal protection attained was 67% with 10 mg/kg of P1G10. The healing rate by 10 mg/kg of P1G10 using the acetic acid ulcerogenic model is similar to that of omeprazole (10 mg/kg) or ranitidine (100 mg/kg). The effect of P1G10 at 10 mg/kg seems to be mediated by an increase in the mucus content by 25% and stimulation of angiogenesis by 64% in a manner similar to growth factors. These results confirm the protective and healing role of proteinases from C. candamarcensis.

Isolation of two plant proteinases in latex from Carica candamarcensis acting as mitogens for mammalian cells.

In a prior study we showed evidence that latex from Carica candamarcensis contains a protein fraction that stimulates mammalian cell proliferation. In this report we describe the isolation of two proteinases responsible for this effect. Both proteinases (P1, P2) display a relative mass of 23 kDa and following chromatographic purification stimulate proliferation of fibroblastic and epithelial cells. P2 added to L929 fibroblasts at 2.5 nM enhances proliferation by 60 %. We further demonstrate that its cellular effect is linked to an increase in activity of Erk2, a component of the MAP kinase pathway. To our knowledge, this is the first known plant proteinase to exert a proliferative effect in mammalian cells. This novel mitogenic property attributed to a purified cysteine proteinase may explain some of the therapeutic actions attributed to these enzymes.