Goro Hori’s research while affiliated with KYOWA HAKKO BIO Co., Ltd. and other places

Inducing expression of the cholesterol-catabolizing enzyme cholesterol 7alpha-hydroxylase (CYP7A1) in the liver can be an effective strategy in preventing hypercholesterolemia and atherosclerosis. We used HepG2 cells to investigate the effects of 1 mM dipeptides having a C-terminal lysine group on the CYP7A1 mRNA level. We found that the dipeptides Asp-Lys, Glu-Lys, and Trp-Lys significantly increased the CYP7A1 mRNA level.

Objectives: To evaluate the effects of the miso soup containing soy protein hydrolyzate with bound phospholipids (c-SPHP) on the serum cholesterol levels in hypercholesterolemic subjects in a randomized double-blind study was carried out over a three-month period. Methods: Subjects were Japanese adult male volunteers whose serum total cholesterol levels were between 200-280mg/dL. The subjects were divided into two groups randomly. Each test diet was orally administered in a miso soup form that contained c-SPHP or casein hydrolyzate (placebo). The subjects were given one test diet daily (c-SPHP 3g/day). The study consisted of a two-week pre-feeding period, a three-month feeding period, followed by a two-week post-feeding period. Results: After three months of miso soup ingestion, serum total cholesterol of c-SPHP-miso soup group (n = 11) decreased significantly compared with the placebo group (n = 11) (p < 0.05) and from the initial level (7.6%, p < 0.01). LDL-cholesterol tended to be lower level compared with the placebo group. There was not a significant difference in HDL-cholesterol level throughout the study. Conclusions: This study suggests that miso soup, containing c-SPHP, has also remarkable improving effects similar to c-SPHP on the serum cholesterol levels in hypercholesterolemic subjects.

Objectives: To evaluate the serum cholesterol lowering effects of soy protein hydrolyzate with bound phospholipids (c-SPHP) in tablet form, a randomized double blind placebo-controlled study in mildly hypercholesterolemic subjects was carried out over a twelve-week period. Methods: Subjects were Japanese adult volunteers with mild hypercholesterol. Seventy-five subjects were randomly divided into three groups and each group was given c-SPHP tablet at the dose of 0, 1.5, or 3g per day, respectively. Placebo group received casein hydrolyzate tablets. Tablets were given twice daily. The study consisted of a one-week pre-testing period, a twelve-week testing period, followed by a four-week post-testing period. Results: After twelve weeks of tablet ingestion, serum total cholesterol and LDL-cholesterol levels of c-SPHP-tablet (3g per day) group (n = 25) decreased significantly compared with the placebo group (n = 25) and from the initial level (p < 0.05). No significant difference in HDL-cholesterol level was observed throughout the study. Conclusions: This study suggests that tablet form of c-SPHP (3g per day), has remarkable effects to reduce serum cholesterol levels in mildly hypercholesterolemic subjects.

This study was done to evaluate the effects of soy protein hydrolyzate with bound phospholipids (c-SPHP), on the serum cholesterol levels in hypercholesterolemic subjects over a three-month period. Subjects were Taiwanese adult male volunteers whose serum total cholesterol levels were above 220 mg/dl. Twenty-one subjects were divided into three groups randomly, and each group was given c-SPHP zero, 3, or 6 g per day. Test diets were orally administered in a powdered drink form that contained c-SPHP or casein hydrolyzate (placebo). The subjects were given the test diet four times daily. The study consisted of a two-week pre-feeding period, a three-month feeding period, followed by a two-week post-feeding period. After 3 months of c-SPHP administration, 3 g per day, serum total cholesterol decreased significantly from the initial level (15.0%, p<0.01) and compared with the placebo group (p<0.05). Furthermore, LDL-cholesterol decreased significantly (27.7%, p<0.01) and the LDL/HDL ratio also decreased significantly (47.4%, p<0.01) from the initial levels. These effects of c-SPHP were dose-dependent. This study suggests that c-SPHP has remarkable improving effects on the serum cholesterol levels in hypercholesterolemic subjects.

This experiment was designed to evaluate the effects of casein, soy protein, soy protein with bound phospholipids (SP), soy protein peptic hydrolysate (SPH) or soy protein peptic hydrolysate with bound phospholipids (SPHP) on the micellar solubility of cholesterol and the taurocholate binding capacity in vitro. We also evaluated the effects of various proteins on cholesterol metabolism in rats and Caco-2 cells. SPHP had a significantly greater bile acid-binding capacity than that of SPH in vitro. Micellar cholesterol solubility in vitro was significantly lower in the presence of SPHP compared to casein tryptic hydrolysate (CTH). The cholesterol micelles containing SPHP and SPH significantly suppressed cholesterol uptake by Caco-2 cells compared to the cholesterol micelles containing CTH. Consistent with these findings in the in vivo cholesterol absorption study using radioisotopes, fecal excretion of total steroids was significantly greater in rats fed the SPHP diet compared with those fed the casein, soy protein, SP and SPH diets. Serum total cholesterol was significantly lower in rats fed SPHP than in those fed casein. The concentrations of total lipids and cholesterol in liver were significantly lower in the SPHP-fed group compared with all other groups. These results suggest that the suppression of cholesterol absorption by direct interaction between cholesterol-mixed micelles and SPHP in the jejunal epithelia is part of the mechanism underlying the hypocholesterolemic action of SPHP. SPHP may also inhibit the reabsorption of bile acids in the ileum, thus lowering the serum cholesterol level.

分離大豆タンパク質・酵素分解大豆リン脂質結合体を中性プロテアーゼ処理して得られた難溶性高分子画分の精製物であるSPHP, およびその未精製物であるc-SPHP摂取による血清および肝臓脂質レベルに対する影響について, ラット (Wistar 系雄, 5週齢) を用いた系で検討した。0.5%コレステロールを含む飼料を9日間与えられることにより上昇するラットの血清および肝臓コレステロールレベルに対して, SPHPでは明瞭な上昇抑制と回復の効果が, また, c-SPHPでは明瞭な回復の効果が認められ, さらにそれらの効果はいずれも添加量依存的であった。コレステロール上昇抑制効果が既知である食品素材あるいはc-SPHPを飼料中に5%添加し, 高コレステロール状態からの回復効果を比較したところ, 血清中のコレステロールと中性脂肪および肝臓中性脂肪レベルでは, 低分子化アルギン酸ナトリウム, 難消化性デキストリン, キトサン, あるいは分離大豆タンパク質を与えたいずれの群にも優って, c-SPHPを与えた群で低値を示した。

以下の3種類の調製物について, Caco-2培養細胞およびラットを用いてコレステロール低減作用を比較した。・SPHP-p; ISP-EDPL結合体ペプシン分解物高分子画分・SPHP-s; ISP-EDPL結合体微生物プロテアーゼ分解物高分子画分・c-SPHP; SPHP-s未精製物1) 高コレステロール食摂取により, 生体内コレステロール濃度がすでに顕著に上昇していたラットの食餌中にSPHP-pを20%添加したところ (実験1), 血清および肝臓のコレステロールレベルはコレステロール摂取前の値まで回復した。このときSPHP-pの添加量依存的に効果が増大した。また, たんに食餌中のコレステロールを除去するよりもSPHP-p5%添加により, 血清コレステロールを低減する効果はさらに増大した (実験2)。2) SPHP-sはSPHP-pとほぼ同様な分子量およびアミノ酸組成を示し, Caco-2培養細胞のコレステロール取込み量もSPHP-pと同等に添加量依存的に抑制した。c-SPHPは両者と比較すると若干弱いものの取込み抑制作用を示した。3) 2種類の栄養評価試験系, すなわち高コレステロール食との同時摂取による生体内コレステロール濃度の上昇抑制作用 (実験3) および高コレステロール食摂取によりすでに生体内コレステロールレベルが顕著に上昇した個体における回復作用 (実験4) を検証するいずれの評価系においても, SPHP-sはSPHP-pと同様に強いコレステロール低減作用を示すことが確認された。またc-SPHPは両者と比較すると若干弱いもののコレステロール低減作用を示した。以上の結果から, SPHP-pおよびSPHP-sは腸管におけるコレステロール吸収の抑制が要因と考えられる生体内コレステロール低減作用を有することが確認された。その作用はすでに高コレステロール血症を呈している個体を正常域に回復させることも可能であることが確認された。

The serum cholesterol level in rats was significantly decreased in a group fed on a soyprotein peptic hydrolyzate (SPH) when compared with a group fed on a casein tryptic hydrolyzate (CTH). The fecal excretion of total steroids was significantly greater with rats fed on the SPH diet when compared with the CTH diet. The results of CaCo-2 studies clearly suggest that the suppression of cholesterol absorption in the intestinal epithelia is part of the mechanism for the hypocholesterolemic action induced by SPH.