• Title/Summary/Keyword: Pathologic Effects

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Pear pomace water extract inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes

  • Rhyu, Jin;Kim, Min Sook;You, Mi-Kyoung;Bang, Mi-Ae;Kim, Hyeon-A
    • Nutrition Research and Practice
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    • v.8 no.1
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    • pp.33-39
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    • 2014
  • Obesity occurs when a person's calorie intake exceeds the amount of energy burns, which may lead to pathologic growth of adipocytes and the accumulation of fat in the tissues. In this study, the effect and mechanism of pear pomace extracts on 3T3-L1 adipocyte differentiation and apoptosis of mature adipocytes were investigated. The effects of pear pomace extract on cell viability and the anti-adipogenic and proapoptotic effects were investigated via MTT assay, Oil red O staining, western blot analysis and apoptosis assay. 3T3-L1 preadipocytes were stimulated with DMEM containing 10% FBS, 0.5 mM 3-isobutyl-1-methylxanthine (IBMX), $5{\mu}g/ml$ insulin and $1{\mu}M$ dexamethasone for differentiation to adipocytes. 3T3-L1 cells were cultured with PBS or water extract of pear pomace. Water extract of pear pomace effectively inhibited lipid accumulations and expressions of PPAR-${\gamma}$ and $C/EBP{\alpha}$ in 3T3-L1 cells. It also increased expression of p-AMPK and decreased the expression of SREBP-1c and FAS in 3T3-L1 cells. The induction of apoptosis was observed in 3T3-L1 cells treated with pear pomace. These results indicate that pear pomace water extract inhibits adipogenesis and induces apoptosis of adipocytes and thus can be used as a potential therapeutic substance as part of prevention or treatment strategy for obesity.

Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis

  • Jeong, Ji Eun;Park, Jae Hyun;Kim, Chun Soo;Lee, Sang Lak;Chung, Hai Lee;Kim, Woo Taek;Lee, Eun Joo
    • Clinical and Experimental Pediatrics
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    • v.60 no.6
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    • pp.181-188
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    • 2017
  • Purpose: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes. Methods: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05). Conclusion: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.

Inhibitory Effects of GC, an Extract from Herbs, on $TNF-{\alpha}/IL-1{\beta}$-induced Activation of Human Fibroblast-like Sinoviocytes (계혈등복합방(GC)의 $TNF-\alpha$$IL-1{\beta}$로 유도된 인간 섬유아세포양 활막 세포 활성화 억제 작용)

  • Jang Kwang-Ho;Jin Mi-Rim;Park Hee-Ok;Kim Dong-Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.5
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    • pp.1225-1232
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    • 2005
  • Based on traditional medicine theories, GC, an extract from 5 herbs, has been formulated and prescribed for the treatment of human rheumatoid arthritis(hRA) for many years. The present studies was done to investigate whether GC has inhibitory effects on activation of fibroblast-like sinoviocytes isolated from a RA patient. In tumor necrosis factor-${\alpha}(TNF-{\alpha}$)/ interleukin-IL-$1{\beta}$(IL-$1{\beta}$) treated human sinoviocytes, the mRNA expression of molecular indicators related to pathologic changes of the sinoviocytes were examined using quantitative real-time PCR. The treatment of GC($10{\mu}g/ml$) significantly suppressed the expression of proinflammatory cytokines and chemokines such as $TNF-{\alpha}$, IL-6 and IL-8 compared with the control, but not $IL-1{\beta}$, The mRNA level of intracellular adhesion molecule-1 (ICAM-1) which is known to increase in the activated sinoviocytes of RA patients, was slightly decreased by GC. The expression of NOS-II was considerably reduced, which was accompanied by a decrease in the production of nitric oxide(NO). Furthermore, GC dramatically raised the mRNA levels of tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), while those of matrix metalloproteinase-3 were significantly lowered. Taken together, these data suggested that GC might suppress the activation of sinoviocytes in hRA.

Clinical Effect of Korean Red Ginseng on Osteoporosis (홍삼의 골다공증에 대한 임상적 효능 연구)

  • 김남현;이환모
    • Journal of Ginseng Research
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    • v.22 no.2
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    • pp.114-121
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    • 1998
  • Osteoporosis is defined as a pathologic condition in which there occurs no change in the chemical composition of the bone, while bone resorption is abnormally increased. This compares with osteogenesis, which leads to a decrease in the amount of bone. Though many varieties of therapies have been tried, no fully effective method has been found. Korean red ginseng is an important variety of Korean ginsengs and many studies have been performed to investigate its effectiveness. But there has been no report on red ginseng's effects on osteoporosis. The purpose of this study was to determine the clinical effects of Korean red ginseng on postmenopausal osteoporosis patients. The study was designed as a double-blind study. Group I consisted of 30 postmenopausal osteoporosis patients who were administered red ginseng extracts and 15 patients who were administered maltose capsules, were included in group II. The following results were obtained after one-year administration to both groups. 1. There were no significant differences in the degree of wedging, number of compression fractures in the vertebral body, trabeculations, and Cobb's angles between the experimental and control groups. 2. Even though bone mineral density increased in the lumbar spine, and decreased in the femur, there was no significant statistical difference. 3. The serum levels of parathyroid hormone (PTH), calcium, phosphate, and alkaline phosphates showed no difference between the two groups regardless of treatment. 4. Urine Deoxy-pyridinoline (DPYD) decreased in the red ginseng group while it increased in the maltose group, but statistically there was no significant difference between the two groups. 5. The clinical presentations showed no significant differences using Visual Analog Scale. 6. The specific complications related with the long-term use of red ginseng did not occur in all patients. In conclusion, there were no statistically significant differences in clinical presentations, biochemical, and radiological studies between the red gins eng and maltose groups. No definite effectiveness of red ginseng on patients with osteoporosis was found.

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Effects of Gami-Choakwiyeum on the PPAR-${\gamma}$ in the Bronchial sthma Mouse Model (천식 쥐 모델에서 가마좌귀음이 PPAR-${\gamma}$에 미치는 영향)

  • Lee, Hai-Ja
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1593-1597
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    • 2006
  • We hope to evaluate the effects of Gami-Choakwiyeum (GCKY) on the PPAR-${\gamma}$’ in the OVA induced asthma mouse model. Female BALB/c mice, 8 weeks of age and free of murine specific pathogens were used. Mice were sensitized by intraperitoneal injection of OVA emulsified in aluminum hydroxide in a total volume of 200 ${\mu}{\ell}$ on one day and 14 days. On 21, 22, and 23 days after the initial intraperitoneal injection of OVA, the mice were challenged using an ultrasonic nebulizer. GCKY was administered 7 times by oral gavage at 24 hour intervals fromdays 19 after intraperitoneal injection of OVA. Bronchoalveolar lavage was perfromed 72 hours after the last challenge, and total cell numbers in the BAL fluid were counted. Also, the level of PPAR-${\gamma}$ of normal and OVA-induced asthma moused with/without administration of GCKY were measured by Western blot analysis. For the histologic examination, the specimens were stained with hematoxylin 2 and eosin-Y.(H & E). Numbers of total cells were increased significantly at 72 h after OVA inhalation compared with numbers of total cells in the normal and the administration of GCKY. Especially, the increased numbers of eosinophils in BAL fluids after OVA inhalation were significantly increased. However, the numbers of eosinophils reduced by the administration of GCKY. Western blot analysis revealed that PPAR-${\gamma}$ levels in nuclear level were increased slightly after OVA inhalation compared with the levels in the normal group. After the administration of GCKY, PPAR-${\gamma}$ levels in cytosolic and nuclear levels at 72 h after OVA inhalation were markedly increased. On pathologic examination, there were many acute inflammatory cells around the alveoli, bronchioles, and airway lumen of mice with OVA-induced asthma compared with inflammatory cells in the normal group. However, acute inflammatory cells around alveoli, bronchioles, and airway lumen markedly decreased after administration of GCKY, GCKY can increase a PPAR-${\gamma}$ level and could be an effective treatment in asthma patients through the PPAR-${\gamma}$ mechanism for bronchial asthma.

Suppression of Spontaneous Dermatitis in Nc/Nga Atopic Model by Gamipaidok-san, a Traditional Herbal Medicine (가미패독산(加味敗毒散) 경구 투여에 의한 Nc/Nga 생쥐의 아토피 피부염 억제 작용)

  • Jin, Ga-Hyun;Jin, Mi-Rim;Choi, Jeung-Mok;Yun, Mi-Young;Kim, Dong-Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.866-874
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    • 2006
  • Atopic dermitiis(AD) is a chronic inflammatory skin disease, which requires safe and effective medicinal therapy. Over production of Th2 cytokines and chemokines as well as IgE, which are mediated by highly activated immune cells, have been considered as pathologic factors in this disease. We found that Gamipaidok-san(GPDS), which is a traditional herbal medicine clinically prescribing for atopic dermitis patients in the hospital, has suppressive effects on the development of DNC8 induced dermatitis in Nc/Nga atopic model. Oral administration of GPDS at the concentration of 250 mg/Kg for 12 weeks significantly suppressed the clinical severity of the dermatitis including pruities, edema, eczematous and dryness. Histological examination revealed that thickness of dermis and epidermis were considerably reduced, and the number of infiltrated inflammatory immune cells including mast cells, CCR3+, and CD4+ T cells were decreased in the affected skin and ear, and consistantly, the number of CD3+/CCR3+ cells in Iymph nodes were decreased. The levels of Th2 cytokines produced by activated splenocyte from atopic mice were also down-regulated by GPDS. Furthermore, the serum levels of IgE were considerably reduced, which accompanied by a decrease in the number of B220+IgE+ B cells in the Iymph nodes. Taken together, these results suggested that oral administration of GPDS, a traditional herbal medicine, has suppressive effects on atopic dermitis of Nc/Nga mouse by the modulation of the immune system, therefore GPDS has potential as a natural therapeutic for treatment of atopic dermatitis.

Korean red ginseng suppresses mitochondrial apoptotic pathway in denervation-induced skeletal muscle atrophy

  • Ji-Soo Jeong;Jeong-Won Kim;Jin-Hwa Kim;Chang-Yeop Kim;Je-Won Ko;Tae-Won Kim
    • Journal of Ginseng Research
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    • v.48 no.1
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    • pp.52-58
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    • 2024
  • Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

Comparative Study of Effects of 'Intramuscular Bee Venom Herbal Acupuncture' and 'Intracutaneous Bee Venom Herbal Acupuncture' in Knee Osteoarthritis Patients (퇴행성 슬관절염 환자에서 근육 내 봉독약침과 피내 봉독약침의 효능 비교연구)

  • Kim, Haeng-Beom;Lee, Ro-Min;Lee, Min-Ho;Choi, Yang-Sik;Kim, Jong-In;Lee, Yun-Ho;Lee, Jae-Dong
    • Journal of Acupuncture Research
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    • v.25 no.2
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    • pp.151-164
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    • 2008
  • Objectives : This study was designed to compare the effects on Korean Western Ontario and McMaster Universities Osteoarthritis Index(KWOMAC), 36-ltems Short-Form Health Survey(SF-36), Visual Analog Scale(VAS) and Nine Point Scale between 'Intramuscular Bee Venom Herbal Acupuncture' and 'Intracutaneous Bee Venom Herbal Acupuncture' in knee osteoarthritis patients for 4weeks. Methods : All the voluntary subject were diagnosed as knee osteoarthritis. Patients were randomly assigned either to two groups : Intramuscular bee venom herbal acupuncture treatment group(IM-BV group) or Intracutaneous bee venom herbal acupuncture treatment group(IC-BV group). The IM-BV group received bee venom herbal acupuncture intramuscularly on muscles closest to the pathologic site on ultrasonography. The IC-BV group received bee venom herbal acupuncture intracutaneously on $LE_{110}$, $LE_{201}$, $ST_{35}$, $ST_{36}$ and $LR_8$. Bee venom herbal acupuncture was applied twice a week for 4 weeks by an oriental medical doctor at Kyung-hee Oriental Medical Hospital. Both groups were checked of pathologic site by ultrasonography before treatment and follow up after four-week treatment. The patients were assessed by KWOMAC and SF-36 before and after four-week treatment. The changes in patients' pain was measured by VAS before treatment and after one-, two-, three- and four-week treatment. The patients' overall treatment outcome assesment was measured by Nine Point Scale after four-week treatment. Results : The results were as follows ; 1. The IM-BV group showed significant improvement on total, pain, stiffness and physical function in KWOMAC, and the IC-BV group showed significant improvement on total and physical function in KWOMAC after 4weeks compared to the pre-treatment. In KWOMAC, the IM-BV group showed more improvement on average compared to the IC-BV group, but there were no significant difference between two groups. 2. The IM-BV group showed significant improvement on VAS after one-week treatment. The IC-BV group showed significant improvement on VAS after two-week treatment. But there were no significant difference between two groups. 3. The IM-BV group showed significant improvement on physical functioning(PF) and bodily pain(BP) in SF-36, and the IC-BV group showed significant improvement on vitality(VT) and bodily pain(BP) in SF-36 after 4weeks compared to the pre-treatment. But there were no significant difference between two groups. 4. 88.2% of IM-BV group and 93.3% of IC-BV group graded their improvement as 'Fair' or better on Nine Point Scale. But there were no significant difference between two groups. Conclusions : This study suggests that in the treatment of knee osteoarthtitis patients, effects of 'Intramuscular Bee Venom Herbal Acupuncture' were not different from 'Intracutaneous Bee Venom Herbal Acupuncture' statistically. But both treatment showed effects on pain and physical function in knee osteoarthtitis patients.

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Protective Effects of Gami Yugan-tang on Liver Damage in Rats (흰쥐의 간손상(肝損傷)에 대한 가미유간탕(加味愈肝湯)의 간(肝) 보호효과(保護效果))

  • Jung, Hee;Go, Ho-Yeon;Hsia, Yu-Chun;Yeo, Hyun-Soo;Baik, Jong-Woo;Ko, Seung-Gyu;Park, Jong-Hyung;Jun, Chan-Yong;Kang, Jea-Chun
    • The Journal of Internal Korean Medicine
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    • v.29 no.1
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    • pp.265-277
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    • 2008
  • In order to investigate the protective effects of Gami Yugan-tang on liver damage in rats induced by $CCl_{4}$ and d-galactosamine, the serum transaminase(ALT & AST), alkaline phosphatase(ALP), lactic dehydrogenase(LDH), superoxide dismutase(SOD), catalase, glutathione S-transferase(GST), glutathione peroxidase(GPX) for enzyme activities, and lipid peroxidation were measured. All animals were divided into 4 groups: normal group (untreated), control group (treated with 0.9% saline solution), sample I group (treated with 740mg/kg Gami Yugan-tang), and sample II group (treated with 1,480mg/kg Gami Yugan-tang). The results were as follows : 1. The results of liver damage in rats induced by $CCl_4$ : The protective effects of ALT were displayed in sample I and sample II, and AST, ALP, LDH, SOD, catalase, GST, GPX, and lipid peroxidation were noted in sample II group. It showed slight necrosis of hepatic cell and pathologic changes, for example, inflammatory cells infiltration were improved in sample II group compared to the control group. 2. The results of liver damage in rats induced by d-galactosamine : The inhibitory effects of AST, ALT, LDH, and ALP activities were noted in both sample I and sample II groups. The findings from this experiment suggests that Gami Yugan-tang has protective effects against liver damage in rats induced by $CCl_{4}$ and d-galactosamine.

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Suppressive Effects of JTT on Collagen-Induced Arthritis in Mice (정통탕(定痛湯)이 콜라젠으로 유도한 관절염 동물 병태 모델에 미치는 효과)

  • Cho, Jong-Cheol;Koo, Young-Sun;Kim, Dong-Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.39-49
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    • 2007
  • Rheumatoid arthritis is an autoimmune disease involving multiple joint. In order to access the suppressive effects of JTT on rheumatoid arthritis and it's effects on immune system we investigated whether JTT could suppress the disease progression of collagen-induced arthritis. DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with DW, JTT (200 or 400 mg/kg) or methotrexate (MTX, 30 mg/kg) as a positive control. Oral administration of JTT significantly suppressed the progression of CIA, which extend is comparable to that of MTX. Histological examination reveled that JTT inhibited infiltration of inflammatory cells into affected paw joint and bone erosion and cartilage destruction were greatly reduced compared with control. Total cell number of spleen, lymph node and peripheral blood were significantly reduced. The absolute number of CD19$^+$, CD3$^+$/CD69$^+$, CD4$^+$/CD25$^+$ cell in spleen from JTT treated mice were significantly decreased. The absolute number of CD19$^+$, CD3$^+$, CD3$^+$/CD69$^+$, CD4$^+$, CD4$^+$/CD25$^+$ CD8$^+$, CD49b, CD3/CD49b cells in draining lymph node were significantly increased compared with control. In peripheral blood mononuclear cells of JTT treated mice, the absolute number of CD4$^+$, CD4$^+$/CD25$^+$, CD3$^+$/CD69$^+$ cells were significantly decreased compared with control, while that of CD49b$^+$ was slightly increased. Infiltration of CD3$^+$ cells and CD11b$^+$/Gr-1$^+$ cells into paw joint was significantly reduced in JTT treated mice. The levels of pathologic cytokines including TNF-a and IL-6 in serum were significantly decreased by oral treatment with JTT The levels of IFN-g in the culture supernatant of splenocyte stimulated with CD3$^+$/CD28$^+$ or collagen were dramatically decreased, while the levels of IL-4 was increased under CD3$^+$/CD28$^+$ or collagen stimulation. Rheumatoid factors including IgG, IgM and collagen specific antibody were present much lower in the serum of JTT treated mice than control. Taken together, JTT has suppressive effects on rheumatoid arthritis by modulating immune system, and has potential to use anti-rheumatic arthritic agent in human.