Effects of SKI 306X, a new herbal agent, on proteoglycan degradation in cartilage explant culture and collagenase-induced rabbit osteoarthritis model.

OBJECTIVE: Protective effects of SKI 306X, a natural herbal product extracted from three herbs Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris, on articular cartilage was examined and compared with other osteoarthritis (OA) drugs using in vitro and in vivo models. METHODS: In vitro culture of rabbit articular cartilage explants was used as a model to measure the effects of drugs on the matrix degradation. The recombinant human interleukin-1alpha (rhIL-1alpha, 5 ng/ml) was added to induce proteoglycan (PG) degradation and the degree of PG degradation was assessed by measuring the amount of glycosaminoglycan (GAG) released into the culture medium. In in vivo experiment, collagenase was intraarticularly injected twice into the right knee joint of rabbits to induce OA-like change, and test agents were orally administered once a day for 28 days. The degrees of OA-like changes were evaluated through a histological examination. RESULTS: In vitro study revealed SKI 306X inhibited the degradation of PG in a concentration-dependent manner. Trichosanthes kirilowii, which is one of the major components of SKI 306X, also significantly inhibited the GAG release in cartilage explant culture at 0.3 and 0.1 mg/ml. Dexamethasone and NSAIDs, such as diclofenac and rofecoxib, had no significant effects on the suppression of PG degradation. In in vivo studies, OA-like degeneration of the articular cartilage and synovial tissue was induced by injecting collagenase into the right knee joint of mature rabbits. At a dose of 200 mg/kg, SKI 306X reduced the OA-like histological changes, whereas diclofenac had no effect at 10 mg/kg. CONCLUSION: These results indicate that SKI 306X inhibited PG degradation in cartilage explant culture, and its prophylactic administration significantly protected the knee joint of rabbit from OA-like change in collagenase-induced experimental OA model. This strongly suggests that SKI 306X can be a good OA agent with some cartilage protection activity.

Screening of hexavalent chromium biosorbent from marine algae.

A highly chromate-selective biosorbent with high adsorption capacity was found by examining the chromate adsorption capacities of 48 species of red, brown, or green marine algae sampled from the east coast of Korea. As a result of screening, a red marine alga showed excellent adsorption characteristics. It was identified as Pachymeniopsis sp. The timing of the sampling of Pachymeniopsis sp. did not affect the adsorption capacity of the alga but the optimum period for mass collection was April-May. The alga also showed high selectivity for chromate and its adsorption capacity for other heavy metal ions such as cadmium and manganese was relatively low. An investigation of the adsorption isotherm of Pachymeniopsis sp. as a dried powder for chromate adsorption at 25 degrees C showed Langmuir-type dependence. The maximum chromate adsorption capacity of the selected alga was about 225 mg/g. The desorption of adsorbed chromate from Pachymeniopsis sp. was done by treating samples with 1 N NaOH. It was confirmed that ion exchange type adsorption was observed with anion exchangers but not with cation exchangers. Therefore it is believed that the chromate adsorption is based on the anionic exchange of Pachymeniopsis sp.

Screening of hexavalent chromium biosorbent for marine algae.

A high-chromate-selective biosorbent with high adsorption capacity was sought by examining the chromate adsorption capacities of 48 species of red, brown, or green marine algae sampled from the east coast of Korea. Screening showed a red marine alga to have the most excellent adsorption characteristics among them, and it was identified as Pachymeniopsis sp. The period at which Pachymeniopsis sp. was sampled did not affect the adsorption capacity of the alga, but the optimum period for mass collection was April to May. The alga also showed high selectivity for chromate since its adsorption capacity for other heavy metal ions such as cadmium and manganese ions was relatively low. An investigation of the adsorption isotherm of dried powder of Pachymeniopsis sp. for chromate adsorption at 25 degrees C showed a Langmuir-type dependence. The maximum chromate adsorption capacity of the selected alga was about 225 mg/g. Desorption of the adsorbed chromate from Pachymeniopsis sp. was done by treating the sample with 1 N NaOH. It was confirmed that ion exchange type adsorption was observed with an anion exchanger but not with a cation exchanger. It is therefore believed that the chromate adsorption is based on anionic exchange of Pachymeniopsis sp.

Amino acid substitution within the S2 and S4 transmembrane segments in Shaker potassium channel modulates channel gating.

To investigate of the gating properties in the voltage-activated potassium channel, we have mutated a variety of S2 and S4 residues in the Shaker potassium protein. Results showed that the R365C and R368C, but not the E283C, R362C, R365S, R368S or the ShB-IR, were sensitive to micromolar concentrations of Cd(2+) ions. This indicates that R365 and R368 play a crucial role in the channel gating due to a conformational modulation of the channel structure. Doubly mutated channels of the E283C/R365E and E283C/R368E caused a transient increase in current amplitude, which reached a peak within a few seconds and then decreased toward initial levels, despite the continual presence of Cd(2+). Taken together, our results suggest that E283, R365, and R368 form a network of strong, local, and electrostatic interactions that relate closely to the mechanism of the channel gating.

General pharmacology of the new antiviral agent SK 1899.

The general pharmacological properties of 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)purine (CAS 247081-81-8, SK 1899), a new potential antiviral agent, were investigated in mice, rats, guinea pigs, rabbits, and dogs. The oral administration of 50, 150, and 500 mg/kg of SK 1899 had no effects on the central nervous system except that it slightly increased the spontaneous locomotor activity in mice at a dose of 500 mg/kg. SK 1899 did not disturb either the spontaneous motility or contractor-induced contraction of the isolated organs such as guinea pig ileum, rat uterus, guinea pig vas deferens, and guinea pig trachea at concentrations up to 10(-4) mol/l. It slightly increased the contractile force in the isolated guinea pig atrium at a concentration of 10(-4) mol/l. Following intravenous infusion of 5, 15, and 50 mg/kg of SK 1899 to anesthetized dogs, it did not change the mean arterial pressure, heart rate, left ventricular systolic pressure (LVSP), and respiratory rate, while it slightly increased the left ventricular positive dP/dtmax (LV + dP/dtmax) at a dose of 50 mg/kg. SK 1899 did not induce any significant changes in the intestinal charcoal meal transit in mice, basal gastric juice secretion in rats, and renal function in rats. It did not affect the blood coagulation system and phenolsulfonphthalein secretion in rats. These findings suggest that SK 1899 has a very low potential to induce any adverse pharmacological effects at the doses showing antiviral activity.

Isolation of peptide ligands that inhibit glutamate racemase activity from a random phage display library.

Several new antibacterial agents are currently being developed in response to the emergence of bacterial resistance to existing antibiotic substances. The new agents include compounds that interfere with bacterial membrane function. The peptidoglycan component of the bacterial cell wall is synthesized by glutamate racemase, and this enzyme is responsible for the biosynthesis of d-glutamate, which is an essential component of cell wall peptidoglycan. In this study, we screened a phage display library expressing random dodecapeptides on the surface of bacteriophage against an Escherichia coli glutamate racemase, and isolated specific peptide sequences that bind to the enzyme. Twenty-seven positive phage clones were analyzed, and seven different peptide sequences were obtained. Among them, the peptide sequence His-Pro-Trp-His-Lys-Lys-His-Pro-Asp-Arg-Lys-Thr was found most frequently, suggesting that this peptide might have the highest affinity to glutamate racemase. The positive phage clones and HPWHKKHPDRKT synthetic peptide were able to inhibit glutamate racemase activity in vitro, implying that our peptide inhibitors may be utilized for the molecular design of new potential antibacterial agents targeting cell wall synthesis.

Comparative Effects of Dietary Palm Oil, Perilla Oil, and Soybean Oil on Lipid Profiles in Differently Aged Rats Fed on Hypercholesterolemic Diets.

The effects of palm oil, soybean oil, and perilla oil on the lipid profiles of liver and serum were compared in young (1 month old) and adult (8 months old) rats fed on hypercholesterolemic diets. In young rats, the concentration of serum cholesterol was highest in the order of palm oil (PAO), soybean oil (SBO), and perilla oil (PEO), whereas it was comparable among the groups of adult rats, resulting in an age-dependent increase in the rats fed on PEO. In young rats, but not in adult rats, the ratio of HDL-/total-cholesterol was significantly increased with an increase in the degree of unsaturation of dietary fats. Dietary PAO, when compared with SBO or PEO, prevented the accumulation of liver cholesterol in adult rats, when expressed as mg per liver. No fat-effect on liver cholesterol was seen in young rats. SBO amd PEO, when compared with PAO, markedly enhanced fecal output of bile acids in adult rats. The concentration of serum triacylglycerol showed a fat-dependent response, whereas that of liver triacylglycerol showed both an ageand fat-dependent response. Thus, PAO showed an effect similar to that of SBO on the serum cholesterol level in adult animals fed on a hypercholesterolemic diet.