• Title/Summary/Keyword: ${\beta}$-Alanine

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Effects of the fermented Zizyphus jujuba in the amyloid β25-35-induced Alzheimer's disease mouse model

  • Kim, Min Jeong;Jung, Ji Eun;Lee, Sanghyun;Cho, Eun Ju;Kim, Hyun Young
    • Nutrition Research and Practice
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    • v.15 no.2
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    • pp.173-186
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    • 2021
  • BACKGROUD/OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Due to the increased incidence of dementia, there is a corresponding increase concerning the importance of AD. In this study, we investigated the protective effects conferred by Zizyphus jujuba (Zj) and Zizyphus jujuba fermented by yeast (Zj-Y), on cognitive impairment in an AD mouse model. MATERIALS/METHODS: AD was induced by injecting amyloid beta25-35 (Aβ25-35) in ICR mice, and subsequently 200 mg/kg Zj or Zj-Y was administered daily for 14 days. The cognitive ability of AD mice was observed through behavioral experiments in T-maze, novel object recognition, and Morris water maze tests. We subsequently measured the levels of malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase, and alanine aminotransferase in either tissues or serum. RESULTS: In behavioral tests, deterioration was revealed in the short- and long-term learning and memory functions in the Aβ25-35-injected control group compared to the normal group, indicating that Aβ25-35 injection impairs cognitive functions. However, administration of Zj and Zj-Y improved cognitive function in mice, as compared to the Aβ25-35-injected control mice. In addition, the Aβ25-35 induced elevations of MDA and NO in the brain, kidney, and liver were suppressed after exposure to Zj and Zj-Y. Especially, Zj-Y showed stronger scavenging effect against MDA and NO, as compared to Zj. CONCLUSIONS: Results of the present study indicate that Zj-Y exerts a protective effect on cognitive impairment and memory dysfunction, which is exerted by attenuating the oxidative stress induced by Aβ25-35.

Casein kinase 2 promotes the TGF-β-induced activation of α-tubulin acetyltransferase 1 in fibroblasts cultured on a soft matrix

  • You, Eunae;Jeong, Jangho;Lee, Jieun;Keum, Seula;Hwang, Ye Eun;Choi, Jee-Hye;Rhee, Sangmyung
    • BMB Reports
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    • v.55 no.4
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    • pp.192-197
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    • 2022
  • Cell signals for growth factors depend on the mechanical properties of the extracellular matrix (ECM) surrounding the cells. Microtubule acetylation is involved in the transforming growth factor (TGF)-β-induced myofibroblast differentiation in the soft ECM. However, the mechanism of activation of α-tubulin acetyltransferase 1 (α-TAT1), a major α-tubulin acetyltransferase, in the soft ECM is not well defined. Here, we found that casein kinase 2 (CK2) is required for the TGF-β-induced activation of α-TAT1 that promotes microtubule acetylation in the soft matrix. Genetic mutation and pharmacological inhibition of CK2 catalytic activity specifically reduced microtubule acetylation in the cells cultured on a soft matrix rather than those cultured on a stiff matrix. Immunoprecipitation analysis showed that CK2α, a catalytic subunit of CK2, directly bound to the C-terminal domain of α-TAT1, and this interaction was more prominent in the cells cultured on the soft matrix. Moreover, the substitution of alanine with serine, the 236th amino acid located at the C-terminus, which contains the CK2-binding site of α-TAT1, significantly abrogated the TGF-β-induced microtubule acetylation in the soft matrix, indicating that the successful binding of CK2 and the C-terminus of α-TAT1 led to the phosphorylation of serine at the 236th position of amino acids in α-TAT1 and regulation of its catalytic activity. Taken together, our findings provide novel insights into the molecular mechanisms underlying the TGF-β-induced activation of α-TAT1 in a soft matrix.

Extractive Nitrogenous Constituents in the Commercial Marine Seasoned-dried Products and Seasoned-dried and Roasted Products (시판 수산조미건제품의 함질소 엑스성분 조성)

  • Park, Choon-Kyu;Park, Jung-Nim
    • Korean Journal of Food Science and Technology
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    • v.34 no.3
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    • pp.370-379
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    • 2002
  • The composition of extractive nitrogenous constituents in four species of commercial marine seasoned-dried products (SDP) and five species of seasoned-dried and roasted products (SDRP) were analyzed. The extractive nitrogen contents were $688{\sim}1,124$ and $756{\sim}1,099\;mg/100g$ in SDP and SDRP extracts. Contents of Free amino acids such as glutamic acid, taurine, arginine, proline, alanine, and histidine were high in all samples. The combined amino acid amounted to $662{\sim}2,248$ and $1,146{\sim}1,821\;mg/100g$ in SDP and SDRP, respectively, which corresponded to 34.5 and 42.5% of the total free amino acid level. ATP and related compounds were $3.69{\sim}7.37$ and $2.17{\sim}8.45\;{\mu}mol/g$ in SDP and SDRP, respectively. Five types of betaines were detected in both specimens although in small amounts. TMAO, TMA, creatine, and creatinine were detected in both samples, however they have same variation in each sample. There was no significant difference in the extractive nitrogenous constituents between SDP and SDRP except in moisture, salinity, and contents of glutamic acid and creatinin (p<0.01).

A Study on the Effect of Erycibae Caulis and Corydalis Tuber Pharmacopuncture on a Mouse Model with Collagen Induced Rheumatoid Arthritis (정공등현호색(丁公藤玄胡索) 약침(藥鍼)이 류마티스 관절염 생쥐 모델에 미치는 영향)

  • Kim, Hyun Ji;Jeon, Ju Hyun;Kim, Young Il
    • Journal of Acupuncture Research
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    • v.33 no.2
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    • pp.21-34
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    • 2016
  • Objectives : The aim of the present study is to examine the effect and mechanism of Erycibae Caulis and Corydalis Tuber Pharmacopuncture (ECP) on a mouse model with collagen induced rheumatoid arthritis (CIA). Methods : We evaluated the Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Creatinine, and the Blood urea nitrogen (BUN) of serum to examine the safety of this study. In vivo, we compared the results of the non-treated group, the normal saline pharmacopuncture treated control group, the indomethacin treated group and the ECP group. We evaluated rheumatoid arthritis manifestation and the Rheumatoid Arthritis Index (AI). Also, immune cells in blood affected by ECP were evaluated by calculating the level of white blood cells (WBC), neutrophil, lympocytes and monocytes. Next, the level of Immunoglobulin M (IgM), Immunoglobulin G (IgG), Interleukin (IL)-$1{\beta}$, IL-6, IL-17, Tumor Necrosis Factor (TNF)-${\alpha}$ and Granulocyte-macrophage Stimulating Factor (GM-CSF)in serum were measured. We examined the imaging of cartilage degeneration using micro CT-arthrography of the hind paw. Additionally, we examined the effects of reducing bone volume (BV) ratio and bone surface/bone volume (BS/BV) ratio with 3D Micro-CT. Finally, we did a histopathologic examination analysis. Results : The absence of liver and kidney toxicity was evident. In vivo, edema of the joints of the ECP group decreased greatly in macroscopic observation. AI measurement of the ECP group also decreased significantly compared to the control group. The level of WBC, neutrophil, lympocytes, and monocytes in the blood decreased but there was no statistical significance of this data. IgM of the ECP group decreased significantly compared to the control group. IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and GM-CSF production of the ECP group decreased significantly compared to the control group. As a result of examining joint condition with 3D micro CT, deformation and destruction of the joint was shown to have decreased. Bone density of ECP group increased at a statistically significant level compared to the control group. Degree of joint inflammation of ECP group decreased significantly compared to the control group. After H&E and M-T staining, infiltration of immune cells, subsidence of the cartilage, damage to the synovial cells and joint erosion decreased. Conclusion : This study showed that ECP hindered the process of rheumatoid arthritis and protected joints and cartilage.

Intragastrically Applicated CCl4-Thiopental Sodium Enhanced Lipid Peroxidation and Liver Fibrosis (Cirrhosis) in Rat: Malonedialdehyde as a Parameter of Lipid Peroxidation Correlated with Hydroxyproline as a Parameter of Collagen Synthesis (Deposition)

  • Kim, Ki-Young;Cho, Syung-Eun;Yu, Byung-Soo
    • Toxicological Research
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    • v.25 no.2
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    • pp.71-78
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    • 2009
  • We investigated the pathogenesis of liver tissue damage during the lipid peroxidation and fibrogenesis with the observation of correlations between the parameters of collagen synthesis (and deposition) and lipid peroxidation in liver fibrosis (cirrhosis) rats. Rats were randomly divided into two groups, normal and $CCl_4$-thiopental sod. intoxicated group. And the one group was treated intragastrically with the mixture of $CCl_4$-thiopental sod. 3 times per week for 3 weeks. The liver tissue and sera were used for the measurement of hydroxyproline (HYP), malonedialdehyde (MDA) and superoxide dismutase (SOD). Biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total-bilirubin and blood urea nitrogen (BUN) were measured. Additionally, the expression of collagen ${\alpha}1$(III) and $\beta$-actin mRNA was observed by RTPCR. The histological change in liver tissue was also observed by Masson's trichrome and H&E staining. Correlation analysis was carried by Spearman's rho method. All biochemical parameters except total-bilirubin were significantly higher in the $CCl_4$-thiopental sod. treated group than that of the normal group (p < 0.01). In the $CCl_4$-thiopental sod. treated group, Hyp as a parameter of collagen synthesis (deposition) and MDA as a metabolite of lipid peroxidation, were significantly elevated by 1.98 and 2.11 times higher than that of the normal group (p < 0.001) respectively. The activity of SOD in the $CCl_4$-thiopental sod. treated group is decreased significantly by 44.8% (p < 0.001). And collagen ${\alpha}1$(III) mRNA was more expressed in the $CCl_4$-thiopental sod. treated group than that of the normal group. However, the expression of $\beta$-actin mRNA is showed similar in both of groups. A good correlation was observed between the content of hyp and MDA concentration (r = 0.70, n = 40) in the two groups. And the correlation between the levels of hyp and SOD (r = -0.71, n = 25) is also reliable. However, no correlation were observed between MDA concentration and SOD (r = -0.40, n = 25) in the two groups. Elevated levels of MDA in $CCl_4$-thiopental sod. treated rats indicated enhancement of lipid peroxidation, which is accompanied by a decrease in SOD activity. Moreover, we could confirm that the parameters of collagen synthesis (and deposition) is in good correlation with the metabolite of lipid peroxidation (MDA) and the lipid peroxidation antagonizing enzyme (SOD). Hence, we propose that (1) lipid peroxidation and collagen synthesis (and deposition) could be enhanced by intragastrically application of $CCl_4$-thiopental sod. during a short terms. And (2) the intoxication of $CCl_4$-thiopental sod. could be used for monitoring of lipid peroxidation and collagen synthesis (and deposition) for test of antioxidant and antifibrotic agent.

Pharmacokinetics of a new anti-HIV agent VP-0501 and development of its amino acid prodrug for improving oral bioavailability (Anti-HIV agent VP-0501의 생체이용성 향상을 위한 아미노산 프로드럭 개발 및 약물동태연구)

  • Cho, Hee-Jeong;Choi, Kyung-Ae;Sung, Ji-Min;Jeong, Sang-Min;Han, Jin-Soo;Kim, Jin-Suk;Shin, Ho-Chul
    • Korean Journal of Veterinary Research
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    • v.46 no.1
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    • pp.7-12
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    • 2006
  • We have studied pharmacokinetics of a new anti-human immunodeficiency virus (HIV) agent VP-0501 and its amino acid prodrug VP-0501AL which is designed to improve oral bioavailability. After oral administration at 100 mg/kg dose in rats (n = 4), VP-0501 was not detectable in plasma (<50 ng/ml), while after the administration of VP-0501AL, VP-0501 was quantitatively detected, at least for 8 hrs, with Cmax of ca. $2.5{\mu}g/ml$ and AUC of $8hr^{\ast}{\mu}g/ml$. When VP-0501 was intravenously administered at 50mg/kg, this compound appeared at a marginal level in plasma with AUC of $2hr^{\ast}{\mu}g/ml$, $t_{1/2}$ of 2 hr, $C_0$ of $0.7{\mu}g/ml$, and MRT of 3 hr. On the other hand, with intravenous VP-0501AL at the same dose, both the prodrug VP-0501AL and its metabolite VP-0501 appeared comparatively at higher level in the plasma: pharmacokinetic parameters of VP-0501AL including $Vd_{\beta}$, AUC, $t_{1/2,{\beta}}$, $C_0$, $CL_{tot}$, and MRT were ca. 2 L/kg, $70hr^{\ast}{\mu}g/ml$, 2 hr, $180{\mu}g/ml$, 0.7 L/hr/kg, and 1 hr, respectively. These results demonstrate that attachment of amino acid alanine to VP-0501 is an effective approach for improvement of its oral bioavailability. Therefore, VP-0501AL is expected to become a new highly bioavailable and potent anti-AIDS drug candidate/lead compound.

Effects of Mutation at Two Conserved Aspartate Residues and a Serine Residue on Functions of Yeast TSA 1 (Saccharomyces cerevisiae TSA1의 보존된 아스파트산 잔기 및 세린 잔기의 변이가 과산화효소 활성 및 샤페론 활성에 미치는 영향)

  • Lee, Songmi;Cho, Eun Yi;Kim, Kanghwa
    • Microbiology and Biotechnology Letters
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    • v.45 no.1
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    • pp.81-86
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    • 2017
  • Alignment of 967 reference sequences of the typical 2-Cys peroxiredoxin family of proteins revealed that 10 amino acids were conserved, with over 99% identity. To investigate whether the conserved aspartic acid residues and serine residue affect the peroxidase and chaperone activity of the protein, we prepared yeast TSA1 mutant proteins in which aspartic acids at positions 75 and 103 were replaced by valine or asparagine, and serine at position 73 was replaced by alanine. By non-reducing SDS-PAGE, TSA1 and the S73A, D75V and D75N mutants were detected in dimeric form, whereas the D103V and D103N mutants were detected in various forms, ranging from high molecular-weight to monomeric. Compared with wild type TSA1, the D75N mutant exhibited 50% thioredoxin peroxidase activity, and the S73A and D75V mutants showed 25% activity. However, the D103V and D103N mutants showed no peroxidase activity. All proteins, except for the D103V and D103N mutants, exhibited chaperone activity at $43^{\circ}C$. Our results suggest that the two conserved aspartic acid residues and serine residue of TSA1 play important roles in its thioredoxin peroxidase activity, and D103 plays a critical role in its chaperone activity.

감귤과피 유색미의 취반 특성

  • 서성수;노홍균;윤광섭;김순동
    • Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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    • 2003.10a
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    • pp.157-157
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    • 2003
  • 우리나라에서 생산되는 감귤은 지리적 기후 조건으로 내한성이 강한 만다린계 온주밀감이 주종을 이루나 최근 과잉생산으로 인한 가격하락과 수입자유화에 따른 대처의 일환으로 경쟁력이 높은 품종을 장려 보급하고 있다. 감귤의 국내 연간 생산량은 56만 톤으로 과일 전체 생산량의 약 30%를 차지하며 과실의 약 20%가 과피로서 그 일부가 한약재로 쓰이나 대부분이 버려지고 있다. 감귤의 과피에는 carotenoids, bioflavonoids, pectin 및 terpenes가 풍부하게 함유되어 있으며, 천연에서 발견되고 있는 약 300여종의 carotenoids계 색소 중 115종이 감귤에 존재한다. 감귤 과피의 주요 carotenoids로는 비타민 A의 역할을 하는 $\beta$-carotene과 cryptoxanthin을 비롯한 $\beta$-citraurin이며 천연 착색제로 활용되고 있다. 또, 주요 bioflavonoids로는 모세혈관의 수축을 촉진시켜 고혈압 예방과 이로 인한 각종 질환을 방지하는 작용을 가진 hesperidin과 혈액내 LDL 콜레스테롤의 양을 줄이는 작용이 알려진 naringin이 있다. 그 외의 감귤 flavonoids도 항산화작용, antimutagen 활성, 항암, 항알레르기 및 항바이러스 효과가 알려져 있다. 밀감 과피의 bioflavonoids는 약 60여종이 분리되어 그 구조가 밝혀져 있으나 90% 이상이 hesperidin이다. 또 과피유에는 $\delta$-limonene을 주성분으로 하는 휘발성 향미성분이 함유되어 있어 향미 개선제로서의 활용이 기대되고 있다. 본 연구는 최근 식생활의 서구화로 쌀 위주의 식생활에 많은 변화를 가져와 쌀 소비량은 해마다 줄어들고 있는 반면 기능성을 가미한 쌀의 소비가 늘고 있음을 감안하여, 우리나라 제주도에서 생산되고 있는 감귤 과피의 물 균질액을 쌀에 코팅하여 아름다운 색상과 기능성을 지닌 유색미를 제조함과 동시에 그 취반 특성을 조사하였다. 그 결과 유색미의 색상은 진노랑(L*; 63.6, a*; -7.87, b*; 46.35)으로 취반 후에도 유사한 색상을 나타내었다. Total carotenoids는 감귤과피에서는 10.74mg%, 과피의 물 균질액에는 0.46mg%이었으며 유색미에는 0.l2mg%, 유색미 취반에는 0.05mg%를 나타내었다. Hesperidin은 과피, 물 균질액, 유색미 및 유색미 취반에서 각각 2173.l2mg%, 108.65mg%, 21.73mg% 및 8.67mg%이었으며, naringin은 각각 1468.40mg%, 73.38mg%, 14.62mg% 및 5.87mg%를 나타내었다. 감귤과피의 유리아미노산은 asparagine이 94.22mg%로 가장 높았으며, methionine이 24.88mg%, alanine이 19.64mg%, ${\gamma}$ -aminoisobutylic acid가 15.37mg%로 이들 4종의 아미노산이 전체 유리아미노산함량의 70%를 나타내었다. 유색미 취반에는 백미 취반에 비하여 총 유리아미노산의 함량이 15%정도 증가되었으며, 그 중에서 glutamic acid는 2.5 배가 증가되었다. 감귤과피의 주요 무기질은 K(652.60mg%)와 Ca(222.50mg%)로 전체 무기질 함량의 86%를 차지하였으며 유색미 취반은 백미 취반에 비하여 K는 2.3배, Mn는 76%, Ca, P, Mg은 16~26%, Fe는 13%가 각각 증가되었다. 취반의 경도, 점착성 및 깨짐성은 유색미 취반과 백미 취반간에 차이가 없으나 응집성과 탄력성은 유색미 취반에서 높았다. 색상에 대한 기호도, 구수한 맛 및 종합적인 기호도는 유색미 취반에서 높았으며 단맛, 쓴맛은 백미 취반과 차이를 보이지 않았다.

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Antioxidant and Anti-Inflammatory Effects of Kamisipjeondaebotang in RAW 264.7 Cells (가미십전대보탕의 RAW 264.7 세포에서 항산화 및 항염증 효과)

  • Myung, Jeong-Ho;Lee, Myung-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1271-1277
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    • 2017
  • As Kamisipjeondaebotang (KSD) extract is an herbal ingredient, safety is very important due to possible cell poisoning or heavy metal toxicity to organs when administered to humans or animals. Accordingly, this study examined the antioxidant and anti-inflammatory effects of KSD extract to confirm its medicinal safety by using RAW 264.7 cells after heavy metal screening, functional index test of the liver and kidney, and cell survival rate test. Heavy metals were not found in KSD extracts or were less than standard amounts. Liver function indices such as aspartate aminotransferase and alanine aminotransferase revealed low values and kidney function indices such as creatinine and blood urea nitrogen were not significantly different from the normal group. This proved the safety to the human. RAW 264.7 cells showed no poisoning compared to the control group in terms of survival rate. Regarding the antioxidant effect of KSD extract, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and 2,2'-azino-bis(3-ethylbenzothiazo-line-6-sulphonic acid) radical scavenging activity increased at concentrations over $10{\mu}g/mL$. The anti-inflammatory effect of KSD extract significantly decreased based on the amount of nitric oxide at concentrations of 10 and $100{\mu}g/mL$ compared to the control group. Expression of interleukin (IL)-$1{\beta}$ and IL-6 decreased in a concentration-dependent manner. There was no significant difference in tumor necrosis factor-${\alpha}$ level. Based on the results, KSD can be regarded as a safe antioxidant with anti-inflammatory effects for fracture treatment.

Immuno-stimulating Polysaccharides from the Fruiting Bodies of Fomitella fraxinea (II) -Isolation and characterization of hot-water extracted polysaccharides- (Fomitella fraxinea로부터 분리한 면역활성 다당류 (II) -열수추출 다당류의 분리 및 특성 -)

  • Cho, Soo-Muk;Lee, Jae-Hoon;Han, Sang-Bae;Kim, Hwan-Mook;Yu, Seung-Hun;Yoo, Ick-Dong
    • The Korean Journal of Mycology
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    • v.23 no.4 s.75
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    • pp.340-347
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    • 1995
  • Polysaccharide FHW was extracted from the fruiting bodies of Fomitella fraxinea with hot-water treatment and then fractionated into FHW-I and FHW-II on DEAE-Cellulose chromatography. FHW-I and FCW-II were further purified into FHW-Ia and Ib, FHW-IIa and IIb on gel permeation chromatography, respectively. A small amount of uronic acid was detected and glucose, galactose, fucose, and mannose were found to be main sugars in the polysaccharides. Protein was detected in FHW-Ia, FHW-IIa, and FHW-IIb, but not in FHW-Ib. FHW-Ia was identified to be a fuco-gluco-mannogalactan with molecular weight of 19,000 and FHW-Ib was a gluco-fuco-mannogalactan of 15,000. FHW-IIa and FHW-IIb were galacto-mannoglucan and their molecular weights were estimated to be 31,000 and 9,000, respectively. Both FHW-Ib and FHW-IIb did not show an absorption band characteristic of the ${\beta}-glycosidic$ linkage in IR spectra. FHW-IIb showed a strong immuno-stimulating activity but the other three polysaccharides showed a weak activity.

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