The Proteolytic Fraction From Vasconcellea cundinamarcensis Latex Displays Anti-Inflammatory Effect in A Mouse Model of Acute TNBS-Induced Colitis

Abstract

The proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis, displays gastric protective and healing activities in different skin lesions in mice and human. In an excisional model, this fraction accelerates resolution of lesions and modulates inflammatory mediators. Based on these data, we assessed its anti-inflammatory activity in murine colitis model, induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) adopted by its physiopathological similarity with human colitis. Twenty four hours after colitis induction followed by three days of treatment, P1G10 at 0.3 and 3.0 mg/Kg induced 30% increase in body weight (p < 0.0001) and ~80% reduction in colon macroscopic damage score (p < 0.05) compared to the untreated TNBS-induced colitis group. Histological analyses showed that 0.3 mg/Kg P1G10 reduced the inflammatory profile and tissue damage (47%, p < 0.05) when it was proteolytically active. Compared to TNBS group, 0.3 mg/Kg P1G10 reduced MPO activity (80%, p < 0.01), MCP-1 (47%, p < 0.05) and TNF-α (50%, no significant) and increased IL-10 (330%, p < 0.001) levels in the supernatant of colonic tissue homogenate. P1G10 treatment also reduced COX-2 expression (60%, p < 0.05) and metalloprotease-2 activity (39%, p < 0.05) while increased globet cell density (140%, p < 0.01), that contributes to mucus layer protection in colonic tissue. Taken together, these findings suggest that low doses of active P1G10 promotes lesion resolution, at least in part by its anti-inflammatory activity, in TNBS-colitis model.

Human skin dermis-derived fibroblasts are a kind of functional mesenchymal stromal cells: judgements from surface markers, biological characteristics, to therapeutic efficacy

“…7 A, B). The neutrophil infiltration was an important feature of colitis model [ 23 ]. Myeloperoxidase (MPO) in the model group was significantly increased, indicating the severe neutrophil infiltration in colon.…”

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“…Vasconcellea cundinamarcensis is native to tropical America[ 177 ]. The in vivo investigation revealed that the proteolytic fraction (P1G10) is composed of 14 proteolytic isoforms that protect and repair the stomach by raising mucus content, lowering gastrin levels to avoid hyperacidity, improving excisional wound healing, and boosting PGE2 production[ 178 ]. P1G10 was investigated as a natural antifungal and shown to be capable of inhibiting mycelium development and cell adhesion in B. cinerea by inducing membrane integrity and cell wall degradation[ 179 ].…”

Combined Effect of High Hydrostatic Pressure and Proteolytic Fraction P1G10 from Vasconcellea cundinamarcensis Latex against Botrytis cinerea in Grape Juice

“…Therefore, peptidases can degrade membrane proteins by altering their permeability and allowing the uncontrolled flow of substances through the cell [ 24 ]. Regarding the pharmacological properties that have been attributed to P1G10, a recent study that shows a protective effect on gastric ulcers and healing activities in different skin lesions in mice and humans stands out [ 59 ]. Therefore, in addition to the antifungal activity that P1G10 possesses, this fraction could add value to grape juice.…”