γ-PGA(Poly-γ-glutamic acid) 보충이 흰쥐의 칼슘 흡수율 및 골대사에 미치는 영향

이민숙(Min?Sook Lee),강정일(Jung?Il Kang),김현수(Hyun?Su Kim) 한국식품영양과학회 2006 한국식품영양과학회지 Vol.35 No.3

칼슘은 한국인에게 가장 부족되기 쉬운 영양소로 섭취만큼이나 흡수가 중요한 요인이 되는 미네랄이다. 최근 칼슘흡수 증진에 효과가 있는 소재로 주목받고 있는 폴리감마글루 탐산(γ-PGA; poly-γ-glutamic acid)이 체내 칼슘흡수에 미치는 영향을 알아보기 위해 4주령된 수컷 흰쥐(Sprague Dawley female rats)를 이용하여 3주간 칼슘결핍식이를 급여시켜 칼슘결핍을 유도 후에, γ-PGA 보충식이를 4주간 급여하였다. 실험군은 칼슘결핍군(Ca free group), 칼슘보충군(칼슘1.2% 보충군, total Ca 0.45%), 칼슘과 CPP1% 보충군(칼슘1.2%+CPP1% 보충군), 칼슘과 PGA1% 보충군(칼슘1.2%+γ-PGA1% 보충군), 칼슘과 CP1%+PGA1% 보충군(칼슘1.2%+CPP1%+γ-PGA1% 보충군), 칼슘과 PGA3% 보충군(칼슘1.2%+γ-PGA3% 보충군)으로 구분하였다. 이때 γ-PGA의 효과를 검증하기 위해 γ-PGA와 칼슘흡수 기전이 유사하고 이미 효능이 알려져 있는 casein phosphopeptide 보충군을 실험군에 추가하였다. 식이섭취량은 칼슘결핍군이 다소 낮았으나 유의적인 차이는 없었으며 칼슘섭취량도 유의적 차이 없이 비슷한 수준을 보였다. 변 및 뇨중 칼슘 배설량은 칼슘만을 섭취한 대조군에 비해 γ-PGA보충군에서 유의적으로 낮았다(p<0.05). 칼슘흡수율 또한 그룹간의 유의적 차이를 보여 칼슘만을 섭취한 그룹에 비해 γ-PGA를 함께 보충한 그룹의 흡수율이 30% 더 높은 경향을 보였으며 이는 이미 효능이 알려진 CPP보다 우수한 수준이었다. 골형성 지표인 혈중 ALP를 측정한 결과 대조군에 비해 γ-PGA보충군이 유의적으로(p<0.05) 낮았고, 혈중 칼슘농도는 항상성을 유지하며 그룹간의 유의적 차이 없이 비슷한 수준을 보였으며, OHPr/Cre도 유의적 차이는 없었다. 뼈 중 칼슘함량 및 강도는 칼슘결핍군이 나머지군에 비해 유의하게(p<0.05) 낮았으며, 칼슘함량의 경우 칼슘만을 보충한 그룹에 비해 γ-PGA를 함께 보충한 그룹이 농도 의존적으로 높은 칼슘함량을 보였고(p<0.05), 골강도의 경우는 유의적 차이는 없었으나 γ-PGA를 함께 보충한 그룹이 농도 의존적으로 골강도가 높은 경향을 나타내었다. 결론적으로 칼슘결핍을 유발한 흰쥐에 칼슘만을 보충시켰을 때보다 칼슘과 함께 γ-PGA를 함께 보충했을 경우, 칼슘흡수 증진 및 골대사에 긍정적으로 기여함을 확인할 수 있었다. 그러나 좀 더 명확한 효과 검증을 위해서는 차후 많은 개체수와 장기간의 식이를 통한 반복실험, γ-PGA 섭취수준에 따른 추가실험이 진행되어야 할 것으로 생각된다. This study was conducted to investigate the effect of γ?PGA (γ?poly glutamic acid) on Ca absorption and bone metabolism in rats. Weaned 4?week old male rats were fed Ca?deficient diets for 3 weeks after the adjustment period. Rats were divided into 6 groups and were fed experimental diets for four weeks. Exper? imental groups were basal (Ca deficient), control (Ca diet: Ca 0.45%), CP1 (Ca 0.45%+casein phosphopeptide 1%), PG1 (Ca 0.45%+gamma poly glutamic acid 1%), CPG (Ca 0.45%+casein phosphopeptide 1%+gamma poly glutamic acid 1%) and PG3 (Ca 0.45%+gamma poly glutamic acid 3%). Though daily Ca intake and food intake of experimental groups showed no significant difference that of control group. The values of fecal Ca excretion and urinary Ca excretion in groups fed γ?PGA were significantly lower than that in the control group. The values of Ca absorption in groups fed γ?PGA were significantly higher than that in the control group. The levels of femur Ca in γ?PGA supplemented group were significantly increased compared to the control group. Also, breaking force of femur in γ?PGA supplemented group showed about 40% increase compared to the control group. These results show that γ?PGA supplement could be helpful to increase Ca absorption as well as to intensify the femur strength and to increase the Ca content of femur in rats.

식품 및 환경, 기타 NC/Nga 생쥐에서 분리한 T 세포에서 foxp3+ 세포 활성화에 대한 PGA-LM의 효과

장순남 ( Soon Nam Jang ),김금란 ( Kum Lan Kim ),강상모 ( Sang Mo Kang ) 한국미생물생명공학회 2009 한국미생물·생명공학회지 Vol.37 No.2

Poly-γ-glutamic acid (γ-PGA) was mixed natural flora of Bacillus subtilis, contaminated from cooked soybeans. Also, it was performed to find out the antiallergic activity by using NC/Nga mice, in vitro. The γ-PGA (PGA-HM: PGA-high molecular weight), Molecular weight 300 kDa, was decomposed and made PGA-LM (PGA-low molecular weight) which has molecular weight below 30 kDa by sonication. Therefore, it was same result between PGA-HM and PGA-LM, and reported PGA-LM as basic result. We found that PGA-LM contains antiallergic efficacy that inhibit B cells and Th2 cells activation from isolated CD4+T cells in NC/Nga atopic dermatitis model mice, and not show a cytotoxicity in the hFCs. To investigate the effects of these PGA-LM in vitro, isolation of splenic B cell and CD4+T cells in atopic dermatitis mice were used. To elucidate the role of PGA-LM in anti-CD40+ interleukin-4 (IL-4)-mediated B-cell activation, showed that the capacity of B cells to expression IL-1β, IL-6, and TNF-α mRNA down-regulated, and IL-10 mRNA up-regulation by PGA-LM treatment, but it had no effect on TGF-β expression. In addition to CD4+IFN-γ+ and CD4+CD25+foxp3+, the functions of PGA-LM in the development of the CD4+CD25+foxp3+ and CD4+IFN-γ+cells, the phenotype and functions of PGA-LM induced CD4+CD25+foxp3+, and CD4+IFN-γ+cells in CD4+T cells. These results suggested that PGA-LM could change cytokine production and generate CD4+CD25+foxp3+Tregs in NC/Nga mice, and may be effective for immunotherapy in patients with AD.

Study on optimal conditions and adsorption kinetics of copper from water by collodion membrane cross-linked poly-γ-glutamic acid

Xiangting Wu,Aiyin Wang,Xiaojie Zheng,Guoxing Li,Xinjiao Dong,Mingjiang Wu 한국화학공학회 2013 Korean Journal of Chemical Engineering Vol.30 No.6

Poly-γ-glutamic acid (γ-PGA) is a novel polyamino acid formed through microorganism fermentation and biosynthesis. In the present test, membrane (PGA-C) formation by γ-PGA and collodion was performed by using 0.1%glutaraldehyde as a cross-linking agent. A study was conducted on the PGA-C adsorption of Cu2+, specifically the related adsorption equilibrium and kinetics, desorption and regeneration. The results show that with an initial solution pH=5.5and at 318 K, the static adsorption isotherm behavior of PGA-C is in compliance with the Langmuir model and is beneficial to the adsorption of the metal. Meanwhile, with the reaction lasting for 30min, adsorption equilibrium was reached with a maximum adsorption capacity up to 7.431 mg/g. The entire reaction process follows the pseudo-second-order kinetics. By using PGA-C, good regeneration results were obtained after adsorption-generation-adsorption cycling with an HCl solution (0.1 mol/L) as regeneration liquid.

The poly-γ-d-glutamic acid capsule surrogate of the Bacillus anthracis capsule induces nitric oxide production via the platelet activating factor receptor signaling pathway

Lee, H.R.,Jeon, J.H.,Park, O.K.,Chun, J.H.,Park, J.,Rhie, G.e. Pergamon Press 2015 Molecular immunology Vol.68 No.2

The poly-γ-d-glutamic acid (PGA) capsule, a major virulence factor of Bacillus anthracis, confers protection of the bacillus from phagocytosis and allows its unimpeded growth in the host. PGA capsules released from B. anthracis are associated with lethal toxin in the blood of experimentally infected animals and enhance the cytotoxic effect of lethal toxin on macrophages. In addition, PGA capsule itself activates macrophages and dendritic cells to produce proinflammatory cytokine such as IL-1β, indicating multiple roles of PGA capsule in anthrax pathogenesis. Here we report that PGA capsule of Bacillus licheniformis, a surrogate of B. anthracis capsule, induces production of nitric oxide (NO) in RAW264.7 cells and bone marrow-derived macrophages. NO production was induced by PGA in a dose-dependent manner and was markedly reduced by inhibitors of inducible NO synthase (iNOS), suggesting iNOS-dependent production of NO. Induction of NO production by PGA was not observed in macrophages from TLR2-deficient mice and was also substantially inhibited in RAW264.7 cells by pretreatment of TLR2 blocking antibody. Subsequently, the downstream signaling events such as ERK, JNK and p38 of MAPK pathways as well as NF-κB activation were required for PGA-induced NO production. In addition, the induced NO production was significantly suppressed by treatment with antagonists of platelet activating factor receptor (PAFR) or PAFR siRNA, and mediated through PAFR/Jak2/STAT-1 signaling pathway. These findings suggest that PGA capsule induces NO production in macrophages by triggering both TLR2 and PAFR signaling pathways which lead to activation of NF-kB and STAT-1, respectively.

Streptozotocin 유발 당뇨 쥐에서 대두와 청국장 및 Poly-γ-Glutamic Acid 분말식이의 항당뇨 효과

문진아(Jin-Ah Moon),왕수경(Soo-Gyoung Wang),오선영(Sun-Young Oh) 한국엔터테인먼트산업학회 2013 한국엔터테인먼트산업학회논문지 Vol.7 No.3

본 연구는 콩식이에 따른 항당뇨 효능 실험으로 성인들의 당뇨예방 및 치료에 도움을 주고자 하는 목적으로 날콩, 볶은콩, 청국장과 γ-PGA 분말을 AIG-93G에 첨가한 식이를 STZ로 유발된 당뇨 흰쥐에게 4주간 섭취시킨 후 혈당, 지질함량 및 장기무게에 미치는 영향을 분석하였다. 실험결과는 PASW를 이용하여 평균, 표준편차를 구하였고, One-way analysis of variance tset를 한 후 각 실험군간의 유의차 검증을 확인하였으며, 다음과 같은 결과를 얻었다. 첫째, 실험동물의 체중변화는 당뇨유발 후 정상군 이외의 모든 군이 유의적으로 감소하였으며, 날콩군과 γ-PGA군은 당뇨대조군에 비해 체중이 증가하였다. 둘째, 간장과 신장 좌·우 장기무게의 경우 정상군에 비해 모든 당뇨유발군은 증가하였다. 셋째, 혈중 포도당의 농도를 측정한 결과 당뇨유발 후 정상군보다 모든 당뇨유발군이 혈당이 증가하였으며, γ-PGA군과 날콩군은 유의적으로 낮은 혈당수준을 보여주었다. 넷째, 실험 5주째 희생 후 측정한 혈청 총 중성지방은 γ-PGA군에 비해 모든 군들 또한 유의적으로 감소하였다. 다섯째, 간장의 단백질 함량은 정상군에 비해 모든 당뇨유발군이 높았고, 당뇨군에 비해 모든 실험군이 유의적으로 높았다. In this research, the influence that it reaches to the blood sugar and lipid content and internal organ weight after during 4 weeks to the diabetes white rat caused the diet adding the unroasted bean, roasted bean, chunggukjang and γ-PGA powder as the experiment looking at the antidiabetic effect according to a diet to AIG-93G by STZ was analyzed. 1) As to the weight change of the experimental animal, the weight increased the unroasted bean group and γ-PGA group in comparison with the streptozotocin-induced group. As to the diet intake, the chunggukjang and γ-PGA group increased by a significant in comparison with the diabetes group. 2) When converting the weight of an organ into the weight 100g per, all diabetes induced group are considered that they increased in case of the extension liver and kidney left?right internal organ weight in comparison with the normal group but show up in case of the unroasted bean and that the weight of an organ is low for a significant the portliness of bowels and intestines and extension is suppressed. 3) All diabetes induced groups picked up to the blood sugar after the diabetes induction more than the normal group as a result of measuring the concentration of the blood glucose. And γ-PGA group and unroasted bean group showed the blood sugar level which is low for a significant. As to C-peptide, the reduction of the unroasted bean group and γ-PGA group shows the low tendency. This can control the hyperglycemia symptom of the diabetes. 4) The lipid content was measured. Then, γ-PGA group was highest as to serum triglyceride, measured after an experiment 5 weeks sacrifice. As to the neutral lipid of the hepatic tissue, the unroasted bean group was lowest. In the case of the blood serum total cholesterol, the chunggukjang group showed the high tendency. 5) As to the protein content of the liver, all experimental groups were higher than the diabetes group as a significant. In the case of the content of the glycogen, the unroasted bean group was not a significant but it was highest. Therefore, there were the unroasted bean, roasted bean and antidiabetic effect of the chunggukjang γ-PGA. Because particularly, the antidiabetic effect of γ-PGA was high and there seemed to be an effect with the diabetes prevention and therapeutic diet.

Poly-γ-glutamic acid suppresses osteoclastogenesis in human osteoclast precursors and prevents joint damage in a collagen-induced murine arthritis model

Lee, Bitnara,Jo, Sungsin,Kim, Sung-Min,Cho, Mi-La,Park, Sung-Hwan,Youn, Jeehee,Ji, Jong Dae,Kim, Tae-Hwan Elsevier 2018 IMMUNOLOGY LETTERS Vol.203 No.-

<P><B>Abstract</B></P> <P>Poly–γ-glutamic acid (γ-PGA), a natural polymer derived from <I>Bacillus subtilis</I>, shows anti-inflammatory activity. However, the effects of γ-PGA on osteoclasts, which are important cells for joint destruction in inflammatory diseases such as rheumatoid arthritis (RA), have not yet been reported. In this study, we show that γ-PGA markedly inhibits osteoclast differentiation in normal PBMC-derived osteoclast precursors and in synovial fluid macrophages of patients with RA. γ-PGA also reduces RANK expression by down-regulating M-CSF receptors. Additionally, oral administration of γ-PGA attenuated bone destruction in a collagen-induced arthritis (CIA) model, demonstrating decreases in inflammation, cartilage damage, and osteoclast formation in histological analyses. Taken together, these data suggest that γ-PGA could be a good candidate for therapeutic prevention of joint destruction in RA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Poly-γ-glutamic acid (γ-PGA) inhibited osteoclast differentiation in normal PBMC-derived osteoclast precursors and RA synovial fluid macrophages. </LI> <LI> Treatment with γ-PGA suppressed osteoclastogenesis <I>in vitro</I> and <I>in vivo</I>. </LI> <LI> Oral administration of γ-PGA markedly reduced bone destruction in collagen-induced mouse (CIA) model. </LI> </UL> </P>

In Vivo Hair Growth Promotion Effects of Ultra-High Molecular Weight Poly-γ-Glutamic Acid from Bacillus subtilis (Chungkookjang)

( Jae Chul Choi ),( Hiroshi Uyama ),( Chul Hoon Lee ),( Moon Hee Sung ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.3

We investigated the effect of ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) on hair loss in vitro and in vivo. 5-Alpha reductase is an enzyme that metabolizes the male hormone testosterone into dihydrotestosterone. By performing an in vitro experiment to analyze the inhibitory effects of UHMW γ-PGA on 5-alpha reductase activity, we determined that UHMW γ-PGA did in fact inhibit 5-alpha reductase activity, indicating the use of UHMW γ-PGA as a potential 5-alpha reductase inhibitor in the treatment of men with androgenetic alopecia. To evaluate the promotion of hair growth in vivo, we topically applied UHMW γ-PGA and minoxidil on the shaved dorsal skin of telogenic C57BL/6 mice for 4 weeks. At 4 weeks, the groups treated with UHMW γ-PGA showed hair growth on more than 50% of the shaved skin, whereas the control group showed less hair growth. To investigate the progression of hair follicles in the hair cycle, hematoxylin and eosin staining was performed. Histological observations revealed that the appearance of hair follicles was earlier in the UHMW γ-PGA-treated group than in the control group. The number of hair follicles on the relative area of shaved skin in the UHMW γ-PGA-treated group was higher than that observed on the shaved skin in the control group. These results indicate that UHMW γ-PGA can promote hair growth by effectively inducing the anagen phase in telogenic C57BL/6 mice.

High Molecular Weight Poly-Gamma-Glutamic Acid Regulates Lipid Metabolism in Rats Fed a High-Fat Diet and Humans

( Ji Ho Park ),( Jae Chul Choi ),( Moon Hee Sung ),( Jae Heon Kang ),( Moon Jeong Chang ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.7

We investigated the effect of high molecular weight poly-gamma- glutamic acid (hm γ-PGA) on adiposity and lipid metabolism of rats in the presence of an obesity-inducing diet. Thirty-two Sprague-Dawley rats were fed either a normal-fat (11.4% kcal fat, NFC) or high-fat (51% kcal fat, HFC) diet. After 5 weeks, half of each diet-fed group was treated with hm γ-PGA (NFP or HFP) for 4 weeks. The HFC group had significantly higher body weight, visceral fat mass, fasting serum levels of total cholesterol, LDL cholesterol, and leptin, and lower serum HDL cholesterol level compared with those of the NFC group (p < 0.05). Treatment with hm γ-PGA decreased body weight gain and perirenal fat mass (p<0.05), fasting serum total cholesterol, and mRNA expression of glucose-6- phosphate dehydrogenase (G6PD), regardless of dietary fat contents (p < 0.01). However, hm γ-PGA increased serum HDL cholesterol in the HFC group (p < 0.05). In vitro, 3-hydroxy-3-methylglutaryl coenzyme-A (HMGCoA) reductase activity was suppressed by the addition of hm γ-PGA. In agreement with observations in animal study, the supplementation of hm γ-PGA (150 mg/day) to 20 female subjects in an 8-week double-blind, placebocontrolled study resulted in a tendency to decrease total cholesterol and LDL cholesterol concentrations. We thus conclude that dietary supplementation of hm γ-PGA may act as a hypocholestrolemic agent, secondary to its inhibitor effect on HMG-CoA reductase, and decrease abdominal adiposity by decreasing hepatic lipogenesis. The present study is an important first step in establishing the effect of hm γ-PGA on cholesterol levels in rats and humans.

High-Molecular-Weight Poly-Gamma-Glutamate Protects Against Hypertriglyceridemic Effects of a High-Fructose Diet in Rat

( Yeong Hui Jeon ),( Mi Sun Kwak ),( Moon Hee Sung ),( Sun Hee Kim ),( Myung Hwan Kim ),( Moon Jeong Chang ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.6

We studied the effects of 2 different dosages of highmolecular- weight poly-γ-glutamic acid (hm γ-PGA) derived from Bacillus subtilis chungkookjang on lipid metabolism in a high-fructose diet-induced hypertriglyceridemic animal model. For 4 weeks, rats were fed either AIN-93 diet (normal control, NC; n = 10) or modified AIN-93 diet in which cornstarch was substituted with 63% fructose (n = 30) to induce hypertriglyceridemia. After 4 weeks, the hypertriglyceridemic rats were treated with daily oral doses of 0 mg (hypertriglyceridemic control, HC), 2.5 mg (hypertriglyceridemic, low hm γ-PGA, HL), or 5 mg?kg?bw-1?d-1 (hypertriglyceridemic, high hm γ-PGA, HH) hm γ-PGA for 4 weeks. The HL and HH groups exhibited significantly lower levels of serum triglyceride, total cholesterol, LDL cholesterol, and free fatty acids than the HC group. The administration of hm γ-PGA reduced serum ALT and AST levels. The activities of lipogenic enzymes such as hepatic malic enzyme and glucose-6-phosphate dehydrogenase as well as glucose-6-phosphate dehydrogenase mRNA expression were significantly decreased by hm γ-PGA administration (p < 0.05). These results indicate that hm γ- PGA has an anti-hypertriglyceridemic effect in highfructose diet-induced hypertriglyceridemic rats.

Screening of Poly-γ-glutamic Acid (γ-PGA) Producing Bacteria from Environmental Soils

( Wan Taek Ju ),( Yong Su Song ),( Young Ju Kim ),( Woo Jin Jung ),( Ro Dong Park ) 한국키틴키토산학회 2013 한국키틴키토산학회지 Vol.18 No.3

Application of γ-PGA is limited due to the high cost associated with its production. Screening bacterial strains in order to find a more efficient producer is one of the platforms towards overcoming its limited usage. Over the 1500 colonies of bacteria were isolated from soil samples. From them, the 6 isolates, MJ80, CS4-29, HB-31, HB-31c, H1-19, and H1-07, were selected as candidates for γ-PGA production. Based on their morphological and biochemical properties and 16s rDNA sequences, MJ80 and CS4-29 were ultimately identified as Bacillus subtilis, H1-07 as B. thuringiensis, HB-31and HB-31c as B. anthracis, and H1-19 as B. sonorensis. The yield of γ-PGA ranged from 3.28 to 4.4%. It turned out that B. subtilis MJ80 and B. subtilis CS4-29 utilized both glutamic acid (GA) and soybean for γ-PGA production. B. thuringiensis H1-07 was identified as GA-dependent, while the other 3 strains were GA-independent. All strains produced high molecular weight γ-PGA over 200 kDa.