[Analysis of the components of porcine liver hydrolysate and examination of the antioxidant activity and angiotensin converting enzyme (ACE)-inhibiting activity].

Hypertension and oxidant stress predispose to the onset and progression of arteriosclerotic diseases. In this study, the components of two kinds of porcine liver hydrolysates (LH-I and LH-II) were analyzed, and the antioxidant effects and angiotensin converting enzyme (ACE)-inhibiting effects of LH-I and LH-II were examined in vitro. Furthermore, the effects of LH-I and LH-II on the blood pressure were examined in spontaneously hypertensive rats (SHR). The results showed that peptides and amino acids accounted for 70% or more of the constituents of both LH-I and LH-II. The results of gel filtration HPLC showed that most of the nitrogen-containing components were peptides or amino acids with molecular weights of 6000 or less. The DPPH radical scavenging activities of LH-I and LH-II were 55.6 and 38.1 µM Trolox Equivalent/g, respectively. The IC(50) values for the ACE-inhibiting activity of LH-I and LH-II were 0.18 and 0.31 mg/mL, respectively. Oral administration of 1 g/rat of LH-I or LH-II to SHR resulted in significant lowering of the blood pressure. These findings indicate that both LH-I and LH-II have antioxidant activity and ACE-inhibiting activity. Moreover, both exerted a blood pressure-lowering effect in SHR. The antioxidant activity and ACE-inhibiting activity of LH-I and LH-II are presumed to be based on the actions of the component peptides.

[Effects of liver hydrolysate on the blood glucose in metabolic syndrome model rats (SHR/NDmcr-cp)].

Insulin resistance associated with visceral fat obesity has been suggested to be the pathological basis of metabolic syndrome. Many studies have demonstrated increased oxidant stress in diabetic patients and animal models of diabetes mellitus. In this study, the effect of liver hydrolysate administration on the blood glucose was examined in SHR/NDmcr-cp (SHR-cp) rats that show spontaneously occurring metabolic syndrome-like abnormalities. The SHR-cp rats were fed diets containing 5% liver hydrolysate for 12 weeks, and the fasting blood glucose and HbA1c were determined every 3 weeks. After administration of the liver hydrolysate-containing feed for 12 weeks, an oral glucose tolerance test was conducted and the plasma angiotensin II (AngII) concentrations were determined. The liver hydrolysate administration had no effect on the blood insulin levels in the oral glucose tolerance test, but significantly inhibited the d-glucose-induced increases of the blood glucose levels. Furthermore, the liver hydrolysate had almost no effect on the fasting blood glucose level, but tended to inhibit the increase of HbA1c. The plasma AngII concentration after the 12-week administration of liver hydrolysate remained significantly lower than that in the control group. These results indicate that a component of liver hydrolysate inhibits d-glucose-induced increase of the blood glucose level, and may improve insulin resistance. The angiotensin converting enzyme (ACE)-inhibiting effect and antioxidant effect of liver hydrolysate may be involved in this effect.

Anti-arthritic action mechanisms of natural chondroitin sulfate in human articular chondrocytes and synovial fibroblasts.

To clarify the exact anti-arthritic action mechanisms of chondroitin sulfate (CS), we evaluated the effects of CS derived from shark cartilage (CS-SC) composed mainly of chondroitin-6-sulfate and porcine trachea cartilage (CS-PC) composed mostly of chondrotin-4-sulfate on the functions of human articular chondrocytes and synovial fibroblasts. Both CS-SC and CS-PC (from 1 to 100 mug/ml) effectively suppressed the interleukin (IL)-1beta (10 ng/ml)-enhanced gene expression of aggrecanase-1/a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS)-4 and aggrecanase-2/ADAMTS-5 in articular chondrocytes embedded in alginate beads and synovial fibroblasts. In addition, CS-SC and CS-PC overcame the IL-1beta-mediated suppression of the aggrecan core protein mRNA, and suppressed the IL-1beta-enhanced collagenase-3/matrix metalloproteinase (MMP)-13 gene expression in chondrocytes. CS-PC, but not CS-SC effectively recovered the IL-1beta-reduced gene expression of tissue inhibitor of metalloproteinases (TIMP)-3 in chondrocytes, and enhanced the production of TIMP-1 in synovial fibroblasts. It is noteworthy that CS is able to modulate the function of synovial fibroblasts as well as that of chondrocytes. Therefore, CS is very likely to be multifunctional chondroprotective material for degenerative arthritic diseases.