• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.224-230
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• 2024

Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known. Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVA-induced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-β signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.

• Biomedical Science Letters
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• v.16 no.4
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• pp.365-376
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• 2010

The purpose of this study was to clarify the effect of light emitting diode (LED) irradiation on healing of impaired wound and alteration of mast cells in experimental diabetic rats. Twenty-four male Sprague-Dawley rats were divided into four groups: excision (Ex), excision-LED irradiation (Ex-LED), diabetes + excision (DM) and diabetes + excision + LED irradiation (DM-LED). Diabetes was induced in rats by streptozotocin (STZ) injection (70 mg/kg, single dose) and 6 mm punch excision wounds were created on the back after shaving hair. The LED-irradiated rats were treated to a daily dose of $5\;J/cm^2$ LED (630 nm) light for 11 days after surgery, and were killed at day 1, 3, 7 and 11. The lesion and adjacent skin tissues were excised, fixed with 10% buffered formalin and embedded with paraffin. For evaluation of wound healing, hematoxylin-eosin (HE) and Masson trichrome staining were performed. Mast cells (MCs) were stained with toluidine blue (pH 0.5) and quantified using a computerized image analysis system. The proliferation activity of keratinocyte in skin tissues was analyzed on sections immunostained with proliferative cell nuclear antigen (PCNA). The results showed that wound healing rate, collagen density and neo-epidermis length, number of PCNA-positive cells, fibroblasts and mast cells were significantly higher in the LED-irradiated rats than in the DM and Ex rats throughout the periods of experiment. Exceptionally, the number of MCs was significantly lower at day 11 compared with day 7 after surgery in the all groups. These findings suggest that the LED irradiation may promote the tissue repair process by accelerating keratinocyte and fibroblast proliferation and collagen production in normal rats as well as in diabetic rats, and MCs may play an important role at an early stage of skin wound healing in normal and diabetic rats.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.909-922
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• 1997

The purpose of this study was to evaluate the effect of high glucose on prostaglandin E2 production in human gingival fibroblasts and periodontal ligament cells in vitro. In control group, the cells($5{\times}10^4\;cells/ml$) were cultured with Dulbecco's Modified Eagle's Medium contained with 10% fetal bovine serum, 45mg/dl glucose. In experimental groups, glucose was added to the above culture condition at the final glucose concentrations of 100mg/dl(Test group 1), 200mg/dl (Test group 2) and 400mg/dl (Test group 3). Then each group was tested for the cell proliferation rate, protein levels, and prostaglandin E2 production at $\frac{1}{2}$, 1, 2, 5 days. The results were as follows : 1. As glucose concentration increased, cell proliferation rate decreased significantly at 1, 2, 5 days in human gingival fibroblasts and periodontal ligament cells(P<0.01). 2. In human gingival fibroblasts, test group 2 and 3 showed significantly decreased protein levels as compared to control group at 5 days (P<0.01). 3. In human periodontal ligament cells, as glucose concentration increased, protein levels decreased significantly at 2 days and 5 days(P<0.01). 4. Prostaglandin $E_2$ production in human gingival fibroblasts and human periodontal ligament cells significantly increased as glucose concentration increased(P<0.01). results at 5 days showed obvious difference as compared to those at 2 days. From the above results, high glucose appeared to affect cellular activities including cell proliferation rate, protein levels and enhance prostaglandin $E_2$ production. It was assumed that prostaglandin E2 production by high glucose enhances inflammatory reaction and has a toxic effect on human gingival fibroblasts and human periodontal ligament cells. This study suggests that periodontal disease in diabetic patient is related to prostaglandin $E_2$ production.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.12 no.1
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• pp.14-26
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• 1990

This study was undertaken to observe the histopathologic changes of the extraction wounds of diabetic rats when exposed to hyperbaric oxygen. A total of 50 rats (Spraque-Dawley strain) were used, which were all induced with diabetes using streptozotocin before the experiment. The experimental group was exposed to hyperbaric oxygen at 2.5atm. for 2 hours a day during the experimental period. The obtained results were summarized as follows : 1. Severe infiltration of inflammatory cells was observed in the initial stages of both the control and experimental groups. The infiltration showed a decreasing tendency at 3rd week in the experimental group, while severe inflammatory infiltration observed in the control group during the entire experimental period. 2. There was abundant proliferation of capillary blood vessels at 1st week after extraction in the experimental group, while moderate capillary growth in the control group was observed at 1st week after extraction. 3. Osteoblastic activity was started at 1st week after extraction in the experimental group, but there showed markedly delayed appearance in the control group, which showed at 2nd week after extraction. 4. The proliferation of fibroblasts showed rather in the experimental group at 1st week, but it was moderate in the control group at 1st week, 2nd week and 3rd week. 5. Epithelialization of the extraction wound was started at 2 days after extraction and reached its peak at 3rd week in the experimental group, while control group seemed to be delayed and incompleted during the experiment. With regard to these results, hyperbaric oxygen therapy disclosed an effective results on the healing of the extraction wound in diabetic rats under exposure at 2.5 atm for 2 hours daily.

• Korean Journal of Food Science and Technology
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• v.39 no.6
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• pp.701-707
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• 2007

Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.12 no.1
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• pp.1-13
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• 1990

The main objectives of this study was to observe the effects of hyperbaric oxygen therapy on the healing processes of mandibular fracture of streptozotocin-induced diabetic rats. Author used 60 rats (Sprague-Dawley Strain) deviding into control(30) and experimental groups(30). Complete fracture was produced on the left mandibular body of 60rats, rendered hyperbaric oxygen therapy (2 hrs. daily at 2.5 atm.) on experimental group and observed effects of hyperbaric oxygen therapy by microscopically. The obtained results were as follows; 1. Infiltration of inflammatory cells was no significant differences between the control and experimental group until 3rd week, but experimental group showed decreasing tendency after 4th week. 2. Severe proliferation of fibroblasts showed rather rapider in experimental group, at 2nd week, while at 3rd week in control group. 3. Osteoclasts appeared at 1st week in experimental group while at 3rd week in control group, and experimental group showed early bone resorption pattern. 4. Osteoblasts appeared at 1st week in experimental group while at 3rd week in control group, and experimental group showed prominent osteoblastic activity. 5. Moderate proliferation of capillary blood vessels showed in initial stage of experimental group while mild proliferation at 1-2nd week in control group. 6. Formation of cartilaginous callus showed at 4th week in experimental group, while at 6th week in control group. 7. Formation of bony callus showed mildly at 5th week, and moderately at 6th week in experimental group, while no appearance in control group, but complete bony union was not observed even in experimental group throughout this experiment.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.540-567
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• 2003

Metabolic disease such as diabetes, which is caused by stress or imbalanced diet, has been increasing. A diabetic tend to suffer from a delay or difficulty of wound healing. The extract of SHIKON (SK), that is the root of Lithospermun erythrorhison, has been reported to have an effect on healing for normal wound, but has never studies for intractable wound so far. Therefore we examined the effect of SK extract on wound healing with healing impaired mouse model. Full-thickness round wounds were created on the backs of db/db mice and applied SK, and we observed neovascularization and collagen synthesis, distribution of apoptotic cells, and vascular endothelial growth factor (VEGF)- positive cells in granulation tissue. After two weeks, a number of capillary vessel and collagen synthesis were increased in SK-treated wounds. Infiltration of VEGF-positive neutrophils was also seen in the wound, besides apoptotic fibroblasts and endothelial cells were appeared in the granulation tissue. After three weeks, the wound closed completely with SK-treated but not in control. These results suggest that SK enhanced neovascularization by VEGF and this kind of apoptosis process makes the scar smooth. In this study, it is obvious that SK also accelerates healing of intractable wound.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.221-231
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• 2022

Adiponectin (Ad), a 30 kDa molecule, is an anti-diabetic adipokine; although derived from adipose tissue, it performs numerous activities in various other tissues. It binds to its own receptors, namely adiponectin receptor 1(AdipoR1), adiponectin receptor 2 (AdipoR2), and T-cadherin (CDH13). Ad plays several roles, especially as a regulator. It modulates lipid and glucose metabolism and promotes insulin sensitivity. This demonstrates that Ad has a robust correlation with fat metabolism. Furthermore, although Ad is not in direct contact with other tissues, including the skin, it can be delivered to them by diffusion or secretion via the endocrine system. Recently it has been reported that Ad can impact skin cell biology, underscoring its potential as a therapeutic biomarker of skin diseases. In the present review, we have discussed the association between skin cell biology and Ad. To elaborate further, we described the involvement of Ad in the biology of various types of cells in the skin, such as keratinocytes, fibroblasts, melanocytes, and immune cells. Additionally, we postulated that Ad could be employed as a therapeutic target to maintain skin homeostasis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.6
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• pp.951-957
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• 2004

Hypoglycemic effect of Prunus mume (PM) extract containing in Sangjinyangheul-tang and Hwangkeumtang, one of the diabetic herbal medicines, was determined by investigating insulin-like action, insulin sensitizing action and a-glucoamylase suppressing action. Insulin-like activity of 3T3-L1 fibroblast was not shown with the treatment of PM methanol extracts. However, treatment with 20% or 40% PM methanol extracts and differentiation inducers significantly decreased the differentiation of 3T3-L1 fibroblasts to adipocytes. A significant insulin sensitizing activity was observed in 3T3-L1 adipocytes, giving PM extracts (60%, 80% and 100%) with 1 ng/mL insulin to reach glucose uptake level increased by 50 ng/mL of insulin alone. In addition, 20% and 40% methanol extracts of PM suppressed the a-glucoamylase activity by 30% in vitro. However, there was no significant differences in the peak of serum glucose levels and area under the curve in Sprague Dawley male rats treated with PM ethanol extract or cellulose and 2 g maltose or dextrin/kg body weight. These data suggested that PM extracts contain effective insulin sensitizing compounds, lipid synthesis suppressing compounds and possibly a-glucoamylase suppressing compounds. Therefore, PM extracts are beneficial for anti-diabetic treatment in obese diabetic patients.

• Korean Journal of Food Science and Technology
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• v.38 no.1
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• pp.114-120
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• 2006

Anti-diabetic effects of extracts and fractions of Sasa borealis (SB), white lotus roots (LR) and leaves (LL), and their mixture were determined in 3T3-L1 adipocytes and Min6 cells by investigating insulin-sensitizing activity and glucose-stimulated insulin secretion, respectively. SB, LR, LL, and mixture of SB, LR, and LL (3 : 2 : 3) were extracted using 70% ethanol, and m mixture extract was fractionated by XAD-4 column chromatography with serial mixture solvents of methanol and water. Fractional extractions were utilized for anti-diabetic effect assay. SB and LR extracts increased insulin-stimulated glucose uptake, but not as much as mixture of SB, LR, and LL. Significant insulin-sensitizing activities of 20 and 80% methanol fractions of SB, LR, and LL mixture extract were observed in 3T3-L1 adipocytes, giving 0.5 or $5\;{\mu}g/mL$ each fraction with 0.2 nM insulin to attain glucose uptake level similar to that attained by 10 nM insulin alone. Similar to pioglitazone, peroxisome proliferators-activated $receptor-{\gamma}\;(PPAR-{\gamma})$ agonist, 20 and 80% methanol fractions increased adipocytes by stimulating differentiation from fibroblasts and triglyceride synthesis. LL extract and 20, 60, and 80% methanol fractions of the mixture suppressed ${\alpha}-amylase$ activity, but did not modulate insulin secretion capacity of Min6 cells in both low and high glucose media. These data suggest 20 and 80% methanol tractions contain potential insulin sensitizers with functions similar to that of $PPAR-{\gamma}$ agonist. Crude extract of SB, LR, and LL mixture possibly improves glucose utilization by enhancing insulin-stimulated glucose uptake and inhibiting carbohydrate digestion without affecting insulin secretion in vivo.