Anti-Obesity Effect and Signaling Mechanism of Potassium Poly-γ-Glutamate Produced by Bacillus subtilis Chungkookjang in High-Fat Diet-Induced Obese Mice.

The purpose of this work was to examine the effects of potassium poly-γ-glutamate (PGA-K) on mice fed a high-fat diet consisting of 60% of total calories for 12 weeks. PGA-K administration reduced the increase in body weight, epididymal fat, and liver weight caused by a high-fat diet compared to the obese group. The triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, which are blood lipid indicators, were significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. The administration of PGA-K resulted in a significant inhibition of pro-inflammatory cytokines, including tumor necrosis factor α and interleukin 6. Moreover, the levels of leptin and insulin, which are insulin resistance indicators, significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. These results suggest that PGA-K exhibits a protective effect against obesity induced by a high-fat diet, underscoring its potential as a candidate for obesity treatment.

Prebiotic Effects of Poly-Gamma-Glutamate on Bacterial Flora in Murine Gut.

Prebiotics improve the growth or activities of specific microbial genera and species in the gut microbiota in order to confer health benefits to the host. In this study, we investigated the effect of poly-gamma-glutamate (γ-PGA) as a prebiotic on the gut microbiota of mice and the organ distributions of γ-PGA in mice. Pyrosequencing analysis for 16S rRNA genes of bacteria indicated that oral administration of γ-PGA increased the abundance of Lactobacillales while reducing the abundance of Clostridiales in murine guts. It is suggested that oral administration of γ-PGA can be helpful for modulating the gut microbiota as a prebiotic.

Promotion Effects of Ultra-High Molecular Weight Poly-γ-Glutamic Acid on Wound Healing.

We examined the in vivo efficacy of ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) for wound healing. The wound area was measured by a ruler and documented by digital photography before the animals were sacrificed at days 8 and 16 post wounding. The areas of wounds treated with UHMW γ-PGA were significantly decreased on days 8 and 16, as compared with those receiving a control treatment, and more than 70% of the UHMW γ-PGAtreated area was repaired by day 8. Hematoxylin and eosin staining confirmed that the epidermis had regenerated in the UHMW γ-PGA-treated wounds. At 16 days post wounding, collagen pigmentation and cross-linking were increased as compared with the control groups, and greater regeneration of blood vessels had occurred in UHMW γ-PGA-treated groups. Increased levels of transforming growth factor-beta and ß-catenin were also observed in skin samples collected from UHMW γ-PGA-treated animals on days 8 and 16 post incision. Taken together, these findings suggest that UHMW γ-PGA promotes wound healing in vivo.

In vivo hair growth promotion effects of ultra-high molecular weight poly-γ-glutamic acid from Bacillus subtilis (Chungkookjang).

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.

We investigated the effect of high molecular weight polygamma- glutamic acid (hm gamma-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 gamma-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 gamma-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 gamma-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 gamma-PGA. In agreement with observations in animal study, the supplementation of hm gamma-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 gamma-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 gamma-PGA on cholesterol levels in rats and humans.

Effects of ultra high molecular weight poly-gamma-glutamic acid from Bacillus subtilis (chungkookjang) on corneal wound healing.

Poly-gamma-glutamic acid (gamma-PGA) is a natural, edible polypeptide in which glutamate is polymerized via gamma-amide linkages. First, we assessed the eye irritancy potential of gamma PGA in rabbits. Additionally, we studied the effects of gamma-PGA on corneal wound healing, due to the anti inflammatory properties and water retaining abilities of gamma-PGA. In this study, the effects of gamma-PGA on corneal wound healing after an alkali burn were evaluated. Thirty eyes wounded by alkali burning in 30 white rabbits were divided into three groups: group A was treated with 0.1% 5000 kDa gamma-PGA for 2 days, group B was treated with 0.1% hyaluronic acid, and group C was not treated, as a control. The area of corneal epithelial defect was examined at 12, 24, 30, 36, 42, and 48 h after corneal alkali wounding to determine initial wound healing. We found that gamma-PGA promoted corneal wound healing, compared with controls, and showed similar effects to hyaluronic acid. These results indicate that gamma-PGA stimulates corneal wound healing by an anti inflammatory effect and enhancing cell migration and cell proliferation. gamma-PGA is a promising biomaterial that may be a substitute for hyaluronic acid in corneal wound healing treatment.

Association of the G134A and G184C Polymorphisms in the CYP1A1 Gene with Lung Cancer Incidence.

The G184C and G134A single nucleotide polymorphisms (SNPs) of the CYP1A1 gene result in Ala62Pro and Gly45Asp substitutions, respectively. Here, we tested whether these SNPs are associated with an alteration in lung cancer incidence. We examined 80 Korean subjects with lung cancer and 240 age- and sex-matched controls. For each subject, the CYP1A1 gene was PCR amplified and sequenced. We observed that the odds ratio (OR) for lung cancer was 3.37 higher in subjects with the G184C polymorphism than in controls (95% confidence interval (CI), 0.89~12.73, P = 0.07). In contrast, the OR for lung cancer was 1.23 in subjects with the G134A polymorphism compared to controls (95% CI, 0.68~2.20, P = 0.49). The G184C polymorphism exacerbated the effects of smoking on lung cancer development. Gene-smoking interaction analyses revealed that past or present smokers with the G184C polymorphism had a higher incidence of lung cancer (OR, 24.72; 95% CI, 4.48~136.31; P < 0.01) than control smokers (OR, 6.65; 95% CI, 2.72~16.28; P < 0.01). However, there was only a slight difference in the ORs for lung cancer between control smokers and smokers with the G134A polymorphism. These findings suggest that the G184C polymorphism, but not the G134A polymorphism, is associated with an increased risk of lung cancer.

Comparison of natural and Dumon airway stents for the management of benign tracheobronchial stenoses.

OBJECTIVE AND BACKGROUND: To investigate the utility and safety of the 'Natural stent', a newly designed silicone airway stent, the authors compared clinical outcomes and complications in patients who underwent silicone airway stenting for the management of benign airway stenosis. METHODS: The medical records of 94 patients requiring the placement of 100 airway stents (43 Dumon and 57 Natural) were retrospectively reviewed in a tertiary referral hospital. RESULTS: Post-tuberculous stenosis was the leading indication for airway stenting (74%), followed by post-intubation stenosis (21%). After intervention, dyspnoea improved in patients who underwent Dumon (90%) and Natural (86%) stenting. After stabilizing dyspnoea, stents could be successfully removed in half of the patients who underwent Dumon (54%) or Natural (49%) stenting. During a 42-month follow-up period, complication rates were similar in patients who underwent Dumon or Natural stenting. CONCLUSION: Natural airway stent was as effective and safe as Dumon stent for the management of benign tracheobronchial stenoses.

A Peptide with anti-transglutaminase activity decreases lipopolysaccharide-induced lung inflammation in mice.

Octapeptide R2 (KVLDGQDP), which has anti-transglutaminas (TGase) activity, decreases inflammation in allergic conjunctivitis model in guinea pigs. The authors examined the effect of R2 on lipopolysaccharide (LPS)-induced lung injury in BALB/c mice. R2 inhalation significantly decreased neutrophil count and cytokine mRNA expression in the lungs of LPS (25 mg/kg)-treated mice (P < .05). It also showed a tendency for decreased tumor necrosis factor (TNF)-alpha-immunoreactive protein in lung homogenates and significantly decreased TNF-alpha-immunoreactive protein in the serum of LPS-injected mice (P < .05). These results indicate that TGase may be a new therapeutic target in LPS-induced lung inflammation.