Abstract
BackgroundThe Amazonian medicinal plant Sangre de grado (Croton palanostigma) has traditional applications for the treatment of wound healing and inflammation. We sought to characterize two extracts (progrado and zangrado) in terms of safety and oligomeric proanthocyanidin chain length. Additionally progrado was evaluated for antioxidant activity and possible chondroprotective actions.MethodsAcute oral safety and toxicity was tested in rats according under OECD protocol number 420. The profile of proanthocyanidin oligomers was determined by HPLC and progrado's antioxidant activity quantified by the ORAC, NORAC and HORAC assays. Human cartilage explants, obtained from surgical specimens, were used to assess chondroproteciton with activity related to direct inhibitory effects on human matrix metalloproteinase (MMP, gelatinolytic) activity using synovial fluid and chondrocytes activated with IL-1β (10 ng/ml). Additionally, progrado (2–10 μg/ml) was tested for its ability to maintain optimal IGF-1 transcription and translation in cartilage explants and cultured chondrocytes.ResultsBoth progrado and zangrado at doses up to 2000 mg/kg (po) displayed no evidence of toxicity. Oligomeric proanthocyanidin content was high for both progrado (158 mg/kg) and zangrado (124 mg/kg), with zangrado almost entirely composed of short oligomers (<6 mer), whereas the majority of oligomers in progrado exceeded 10 mers. Progrado was a remarkably potent antioxidant in the standardized tests ORAC, NORAC and HORAC. Progrado was exceptionally effective in reducing both basal and IL-1β induced glycosaminoglycan release from human cartilage explants at concentrations that also directly blocked the gelatinolytic activity of MMP-2 and MMP-9. Progrado prevented IL-1β induced suppression of IGF-1 production from human cartilage explants as well as stimulating basal IGF-1 production (P < 0.05). Comparable changes in IGF-1 gene expression were noted in cultured human chondrocytes.ConclusionProgrado has a promising safety profile, significant chondroprotective and antioxidant actions, directly inhibits MMP activity and promotes the production of the cartilage repair factor, IGF-1. This suggests that progrado may offer therapeutic benefits in joint health, wound healing and inflammation.
Highlights
The Amazonian medicinal plant Sangre de grado (Croton palanostigma) has traditional applications for the treatment of wound healing and inflammation
In contrast to the small differences in maximal inhibition by progrado on MMP-2 and MMP-9 activity, within the dose range examined in this protocol, MMP-2 activity appeared to be more sensitive to inhibition by progrado at concentrations below 4 μg/ml. These results clearly show that progrado is an effective inhibitor of the gelatinase activity present in osteoarthritis, and that this actions is demonstrated at the same concentrations of progrado that are chondroprotective and augments the chondrocyte expression and production of IGF-1
In healing gastric ulcers we confirmed that sangre de grado therapy reduces the expression of inducible nitric oxide synthase in the ulcer bed, along with IL-1β, IL-6, TNFα and COX2, so it may limit the tissue burden of peroxynitrite by molecular quenching (NORAC test) and by limiting the production of nitric oxide, peroxynitrite's molecular parent, by suppressing iNOS gene expression [3]
Summary
The Amazonian medicinal plant Sangre de grado (Croton palanostigma) has traditional applications for the treatment of wound healing and inflammation. There is growing interest in natural products as agents to manage health, from a preventative perspective. One factor driving this interest is the advancing age of populations in developed countries and concerns over the nutrient profile and content of Westernized diets and its links to disease or poor health [1]. Sangre de grado is used topically for wound healing, pruritis, analgesia, and taken orally for diarrhea, ulcer healing and severe gastrointestinal distress. It has broad applications within the Amazonian community. There are other mechanistic studies on sangre de grado or its extracts that support the traditional use, especially for gastrointestinal applications [7,8,9]
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