Rheological properties and efficacy of the formulation of hyaluronic acid with tamarind seed polysaccharide for arthritis.

BACKGROUND: Tamarind seed polysaccharide (TSP) is used as a texturizing agent and a thickener in food and pharmaceutical products. There are no publications describing the addition of TSP to intra-articular injection formulations for arthritis. OBJECTIVE: The purpose of this study was to investigate the rheology and efficacy of the formulation of TSP with hyaluronic acid (HA) as a new material for injection for arthritis. METHODS: We investigated the viscoelastic properties of formulations of HA and TSP as potential lubricants for arthritis, and tested the improvement of right/left paw weight distribution in monosodium iodoacetate-induced arthritis in the rat. RESULTS: HA formulations with 3% and 4% TSP showed improved rheological characteristics and were protected against changes induced by heat sterilization. Addition of TSP also reduced pain in the arthritis model, as evidenced by normalization of the distribution of paw weight. CONCLUSIONS: TSP is a potential material as a substitute for HA or in combination with HA for intra-articular injection for arthritis.

Topoisomerase I inactivation by reticulol and its in vivo cytotoxicity against B16F10 melanoma.

To investigate the enzyme-inhibitory efficacy and the cytotoxicity of reticulol produced from a strain of Streptoverticillium, we conducted a DNA topoisomerase (Topo) cleavage assay and an in vivo assay using B16F10 melanoma. From the inhibition assay of reticulol for Topo I, which is involved in melanoma metastasis, it was seen that Topo I treated with 45 microM reticulol did not replicate or transcribe DNA by forming supercoiled DNA. In the annexin V/propidium iodide staining assay to investigate the death pattern of B16F10 cells treated with 200 microM reticulol, proliferation of B16F10 cells was inhibited due to necrosis. Furthermore, from the in vivo assay, reticulol combined with Adriamycin (a mixture with retinolol 5 mg/kg and Adriamycin 1 mg/kg) further retarded the tumor growth compared to that in mice treated with Adriamycin alone (1 mg/kg). The survival rate of tumor-bearing mice treated with the mixture was closely associated with its cytotoxicity. Taken together, these results suggested that reticulol inactivates Topo I, which is involved in tumor metastasis, and exhibits excellent cytotoxic efficacy against B16F10 melanoma, when combined with Adriamycin, in a mouse model.

Antitumor efficacy of reticulol from Streptoverticillium against the lung metastasis model B16F10 melanoma. Lung metastasis inhibition by growth inhibition of melanoma.

Reticulol was isolated from the culture broth of the strain Streptoverticillium sp. NA-4803. Recticulol (M.W. 222.2) exhibited a potent in vitro cytotoxicity against A427, a human lung tumor cell line, and B16F10, a mouse melanoma cell line. In the trypan blue staining assay for B16F10 cells, the cell viability by reticulol treatment was significantly decreased in a dose-dependent manner. The in vivo assay for the lung metastasis-blocking effect showed that reticulol injected intravenously suppressed the increase in colonies on the lung in a dose-dependent manner. In addition, the survival rate of tumor-implanted mice treated with reticulol was closely associated with its antitumoral efficacy. Reticulol administered via the peritoneum of mice showed less metastasis inhibition than that injected intravenously. To demonstrate the mechanism for inhibition of metastasis, the inhibitory effect of reticulol for matrix metalloproteinase-2 or -9 involved in melanoma metastasis was investigated; however, they were not observed on zymogram gel. In addition, the antitumor efficacy of reticulol was not associated with cell cycle arrest or apoptosis. Therefore, it was inferred that reticulol known as a phosphodiesterase inhibitor directly inhibited the growth of B16F10 melanoma, showing necrotic response. These results suggest that reticulol protects its lung metastasis via the bloodstream by inhibiting the growth of B16F10 melanoma at the cellular level.