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Ursolic acid with large amount (0.67% of dried plant weight) along with 7 compounds, namely as spatozoate (1), kaurenoic acid (2), ursonic acid (3), 3-hydroxy-11-ursen-28,13-olide (4), ursolic acid (5), vindoline (6) and mixture of β-sitosterol and stigmasterol were isolated from dichloromethane and ethyl acetate extracts which have shown anti-glucosidase activity of the whole plant of C.roseus. Some isolated compounds and their derivatives were also tested for anti-glucosidase and cytotoxicity.Ursolic acid was examined for hypoglycemic activity in alloxan-induced diabetic mice with dose of 200 and 300 mg/kg/day, respectively. The results have shown that the blood glucose level were reduced by 45.75% and 51.31% to compare with the control group. This study has confirmed that the main component of Vietnamese C. roseus has had significant anti-hyperglycemia activity.
The dysregulation of the metabolism of glycosaminoglycan and protein components of extracellular matrix (ECM) is a typical feature of diabetic complications. High glucose-induced enrichment of ECM with hyaluronan (HA) not only affects tissue structural integrity, but influences cell metabolic response due to the variety of effects depending on the HA polymer molecular weight. TSP-1-dependent activation of TGFβ1 axis is known to mediate numerous matrix disorders in diabetes, but its role concerning HA has not been studied so far. In this work we demonstrated that 30 mM d-glucose increased the incorporation of [3H]glucosamine in high-molecular-weight ( > 2000 kDa) HA of medium and matrix compartments of human mesangial cultures. Simultaneously, the synthesis of HA with lower molecular weight and HA degradation were not altered. The cause of the increased high-molecular-weight HA synthesis consisted in the up-regulation of hyaluronan synthase (HAS) 2 mRNA without alterations of the expression of HAS3, which generates HA of lower molecular weight. d-Glucose at 30 mM also stimulated the production of transforming growth factor β1 (TGFβ1), the excessive activation of which was determined by the up-regulation of thrombospondin-1 (TSP-1). The blockage of TGFβ1 action either by neutralizing anti-TGFβ1 antibodies or by quenching the TGFβ1 activation (with TSP-1-derived synthetic GGWSHW peptide) abolished the effect of high glucose on HAS2 mRNA expression and normalized the synthesis of HA. Exogenous human TGFβ1 had the same effect on HAS2 expression and HA synthesis as high glucose treatment. Therefore, we supposed that TSP-1-dependent TGFβ1 activation is involved in the observed high glucose effect on HA metabolism. Since high-molecular-weight HA polymers, unlike middle- and low-molecular weight HA oligosaccharides, are known to possess anti-inflammatory and anti-fibrotic functions, we suppose that the enrichment of mesangial matrix with high-molecular-weight HA may represent an endogenous mechanism to limit renal injury in diabetes.
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