• The Journal of Korean Medicine
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• v.28 no.3 s.71
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• pp.216-231
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• 2007

Objectives : Chengsimyeunja-eum and Sunghyangjungi-san are prescriptions used for cerebral infarction clinically; it is known that these formulas reduce ischemic damage. According to previous research data, controlling certain types of glucose is considered to decrease the risk of cerebral infarction. Based on this fact, we investigated the effects of Chengsimyeunja-eum and Sunghyangjungi-san extracts on reperfusion following ischemic damage to diabetic rats, the change of c-FOS and Bax positive neurons in the hippocampus and cerebral cortex and protein through immunohistochemical methods, changes of serum glucose level, serum triglyceride level, and hepatic glucokinase activity. Methods : We induced ischemic damaged in diabetic rats, and the rats were administered Chengsimyeunja-eum and Sunghyangjungi-san extracts. Results : Chengsimyeunja-eum demonstrated significant decrease of c-Fos positive neurons in both hippocampus and cerebral cortex as well as a significant decrease of Bax positive neurons in hippocampus after ischemic damage on diabetic rats and decrease of serum glucose level after ischemic damage on diabetic rats. Sunghyangjungi-san demonstrated significant decreases of c-Fos and Bax positive neurons in both hippocampus and cerebral cortex after ischemic damage on diabetic rats. Conclusions : Chengsimyeunja-eum, effect on glucose level control, has a remarkable effect of protection of neurons not effective on glucose level. Sunghyangjungi-san showed neuroprotective effect through preventing neuronal cell death.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.1
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• pp.57-70
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• 2012

The apoptotic process of gastric mucosa triggered by induction of proapoptotic gene expression, such as Bax. Stress-inducing factors may affect Bcl-2/Bax ratio and thus the rate of apoptosis through modulation of the expression of both proteins depending upon the experimental model. TGF-${\beta}$ is believed to be essential in wound healing for regulation of cell growth and differentiation and is known to be involved in tissue repair and remodeling. The polypeptide growth factors, such as vascular endothelial growth factor(VEGF), regulate essential cell functions involved in tissue healing including cell proliferation, migration, and differentiation. The purpose of this study was to investigate whether the oral administration of $Hwangyeon-tang$ (HYT) would have protect effects on gastric ulcer in rat. Sprague-Dawley rats (n=40) were randomly divided into 4 groups ; Normal, Saline, Cimetidine and HYT group. The saline, cimetidine and HYT extract were orally administrated to each group and gastric ulcer was induced with HCl/EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In Results, the wound healing of gastric ulcer was promoted by HYT and the significant alterations of BAX/Bcl-2, TGF-${\beta}1$ and VEGF proteins in gastric mucosa were observed. These results suggest that Fritillaria ussuriensis extract promotes wound healing and has protective effects on gastric ulcer in rats.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3857-3862
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• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.71-77
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• 2011

Gastric ulcer has multifactorial etiology, and the development of ulcer is known to be caused by gastric acidity, pepsin secretion, gastric motility and gastric mucosal blood flow. The ulcer results from the tissue necrosis and apoptotic cell death triggered by mucosal ischemia, free radical formation and cessation of nutrient delivery. The gastric mucosa is usually exposed to a wide range of aggressive insults, and has developed efficient mechanisms to repair tissue injury. The apoptotic process of gastric mucosa is triggered by the induction of such proapoptotic gene expression, such as BAX. The Bcl-2 family of proteins plays a pivotal role in the regulation of apoptosis. The maintenance of gastric mucosa integrity depends upon the ratio between cell proliferation and cell death. Stress-inducing factors may affect Bcl-2/BAX ratio and thus the rate of apoptosis through modulation of the expression of both proteins depends upon the experimental model. In addition to the regulation of apoptosis, new vessels have to be generated in order to ensure an adequate supply of oxygen and nutrients to the healing gastric mucosa. This events are regulated by several factors. Among them, such polypeptide growth factors, such as vascular endothelial growth factor (VEGF) regulates essential cell functions involved in tissue healing including cell proliferation and differentiation. The purpose of this study was carried to investigate whether Rhei Rhizoma administration might protect apoptotic cell death and promote angiogenesis in gastric mucosa. Sprague-Dawley rats were randomly divided into 4 groups; normal, saline, cimetidine and Rhei Rhizoma-treated group. The saline, cimetidine and Rhei Rhizoma extracts were orally administrated to each group and gastric ulcer was induced by HCl-EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In results, Rhei Rhizoma proves to promote to heal wound in gastric ulcer in conclusion and the significant changes of BAX, Bcl-2 and VEGF quantity in gastric mucosa were observed. These results suggest that Rhei Rhizoma extract may promote incision wound healing and has protective effects on gastric ulcer in rats.

• Journal of Acupuncture Research
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• v.33 no.3
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• pp.101-116
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• 2016

Objectives : This research was performed to investigate the effects of Ukgansan pharmacopuncture(U-PA) of focal brain ischemia induced by middle cerebral artery occlusion(MCAO) in rats. Methods : The subjects were divided into 5 groups : A control group, acupuncture group, pharmacopuncture group U-PA1($2.571mg/250g/40{\mu}{\ell}$), pharmacopuncture group U-PA2($6.428mg/250g/40{\mu}{\ell}$), and pharmacopuncture group U-PA3($12.855mg/250g/40{\mu}{\ell}$). The focal brain ischemia was induced by intraluminal filament insertion into the middle cerebral artery. After 3 days of MCAO, Ukgansan(UGS) pharmacopuncture treatment was performed on the GB20, and the day after being treated with pharmacopuncture, the Morris water maze test was carried out by the assigned group. The series of processes were treated 6 times. Thereafter Bax, Bcl-2, Bax/Bcl-2 ratio, mGluR5, density of neuronal cell, and ChAT were measured. Results : The results were as follows. 1. The intensity of Bax significantly decreased in the U-PA1, U-PA2, U-PA3 groups. 2. The Bax/Bcl-2 ratio significantly decreased in the U-PA3 group compared with the control group. 3. The neuroprotective effect on the hippocampal CA1 significantly increased in the U-PA1, U-PA2, U-PA3 groups compared with the control group. 4. The density of ChAT in the hippocampal CA1 significantly increased in the U-PA1, U-PA2, U-PA3 groups compared with the control group. Conclusion : These results suggest that UGS pharmacopuncture may have anti-apoptotic and neuroprotective effects on focal cerebral ischemia caused by intraluminal filament insertion into the middle cerebral artery in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.594-601
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• 2002

The current study was carried out to evaluate neuroprotective effects of Citri Pericarpium after transient global ischemia in gerbils. Male Mongolian gerbils weighing 60-80g were anesthetized with 2% isoflurane mixed with 30% oxygen and 70 % nitrogen. Bilateral common carotid arteries were occluded for 5 minute with microaneurysm dips. On 3 or 7 days after ischemic surgery, the gerbils were sacrificed. The brain were removed, embedded in paraffin and sectioned at 8㎛-thickness. Gerbils that received ischemic insult for 5 min showed extensive neuronal damage in the hippocampal CA1 region, and the number of viable neuronal cell was 51.0±2.5/mm, 32.2% of normal group at 7 days after ischemic surgery. In animals that underwent the extract of Citri Pericarpium treatment, the number of viable neuronal cell were significantly better preserved at 110.58±3.58/mm, 72.0% of normal group than those of ischemic group (P<0.01). In the immunohistochemistry of Bax and Bcl-2, the Citri Pericarpium treated group down-regulated the expression of Bax protein at 72hr after transient global ischemia. In contrast, Bcl-2 protein level was not changed. The appearance in TUNEL assay is similar to the pattern of Bax protein. The water extract of Citri Pericarpium significantly reduced the number of TUNEL-positive CA1 pyramidal neurons at 72hr. The results suggest that Citri Pericarpium has potential neuroprotective effects in the transient global ischemia and the increase in the ratio of Bcl-2 to Bax may contribute to the anti-apoptotic effect of Citri Pericarpium.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.246-253
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• 2014

Codonopsis lanceolata has been used as an herbal medicine for several lung inflammatory diseases, such as asthma, tonsillitis, and pharyngitis. Previously, we showed the neuroprotective effect of steamed and fermented C. lanceolata (SFC) in vitro and in vivo. In the current study, the treatment of HT22 cells with SFC decreased glutamate-induced cell death, suggesting that SFC protected HT22 cells from glutamate-induced cytotoxicity. Based on these, we sought to elucidate the mechanisms of the neuroprotective effect of SFC by measuring the oxidative stress parameters and the expression of Bax and caspase-3 in HT22 cells. SFC reduced contents of ROS, $Ca^{2+}$ and NO. Moreover, SFC restored contents of glutathione and glutathione reductase as well as inhibited Bax and caspase-3 activity in HT22 cells. These results indicate that steamed and fermented C. lanceolata (SFC) extract protected HT22 cells by anti-oxidative effect and inhibition of the expression of Bax and caspase-3.

• Journal of Acupuncture Research
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• v.35 no.4
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• pp.207-213
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• 2018

Background: The purpose of this study was to examine the effect of Dokhwalgisaeng-tang on immobilization-induced muscle atrophy. Methods: Twenty young male Sprague-Dawley rats were divided into 2 groups. The rats in Dokhwalgisaeng-tang group were orally administered Dokhwalgisaeng-tang water extract, and the rats in the control group were given saline only. Hind limb immobilization was performed with casting tape to keep the left ankle joint in a fully extended position. No intervention was performed on the right leg which was used as an intact region. After 2 weeks of immobilization, all animals were sacrificed, and the gastrocnemius muscle was dissected from both legs and weighed. The morphology of the right and the left gastrocnemius muscle in both the Dokhwalgisaeng-tang and the control group was assessed by hematoxylin and eosin staining. The muscle cross sectional area was examined by image analysis (Axiovision LE software). In addition, immunohistochemical staining was carried out using the free-floating method, and the number of apoptotic related proteins were counted (anti-BAX, anti-Bcl-2). Results: Dokhwalgisaeng-tang showed a significant protective effect against the reduction of the left gastrocnemius muscle (weight and muscle cross sectional area) compared with the control group. Moreover, the treatment with Dokhwalgisaeng-tang significantly reduced protein expression of BAX and increased protein expression of Bcl-2 in the gastrocnemius muscle compared with the control group. Conclusion: Dokhwalgisaeng-tang showed protective effects against disuse muscle atrophy, potentially through altered BAX and Bcl-2 protein expression in the gastrocnemius muscle.

• Journal of Korean Medicine Rehabilitation
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• v.27 no.2
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• pp.1-8
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• 2017

Objectives Ethanol is a potent inhibitor of muscle protein synthesis. Muscle mass is regulated by the balance between rates of protein synthesis and protein breakdown. Both acute and chronic alcohol consumption inhibits synthesis to a greater extent than degradation. Protein synthesis is more intensely decreased in type II fibers than in type I fibers. Apoptosis has been shown to occur frequently in a variety of tissues in response to chronic alcohol feeding. Increased muscle fiber apoptosis has been shown in alcoholics with myopathy. Pueraria radix has been used for many disorders such as fevers, gastrointestinal disorders, muscle aches, allergies, respiratory problems, skin problems, high blood pressure, migraine headaches, lowering cholesterol and treating chronic alcoholism. We therefore tested the hypothesis that oral treatment with Pueraria radix could reduce the ethanol-induced muscle atrophy. Methods Young male Sprague-Dawley rats were orally given 25% ethanol (5 ml/kg, body weight) daily with Ethanol for 4 weeks. Normal group was similarly administrated with saline. The Rats of Pueraria radix treated group (EtOH+PR) were orally administrated Pueraria radix water extract, and rats of EtOH group were given with the vehicle only. After 4 week, the morphology of gastrocnemius and plantaris muscles were assessed by hematoxylin and eosin staining. The immunoreactivities of pre-apoptotic BAX and anti-apoptotic Bcl-2 proteins were also measured. Results The muscles from rats of EtOH group represented a significant reduction in average cross section area compared to Normal group. EtOH+PR group had increased fiber compared to the EtOH group. Moreover, to investigate the ethanol-induced muscular apoptosis, the immunohistochemical analysis of Bax and Bcl-2 was carried out. The treatment with Pueraria radix (EtOH+PR) significantly decreased BAX expression and increased Bcl-2 expression 4 weeks after ethanol administration when compared with Normal group. Conclusions These results suggest that Pueraria radix water extract has protective effects on chronic alcohol induced myopathy.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.51-63
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• 2009

Background and Objective : The prospects for developing an anti-apoptotic natural component or a compound that exerts a neuroprotective effect with few or no side effects for the treatment of neurodegenerative disease appear favorable. In the present study, we evaluated the effects of the methanol extract of Phellodendri Cortex (PC extract) on 1-methyl-4-phenyl pyridinium($MPP^+$)-induced apoptosis in PC-12 cells. Materials and Methods : We used the methanol extract of Phellodendri Cortex (PC extract). PC-12 cells were cultured by RPMZ-1640. We found the PC extract's gene expression (Bax, Bcl-2) by using RT-PCR. We examined the PC extract's protein expression (Bcl-2, Bax, cytochrome c, poly (ADP-ribose) polymerase (PARP), caspase-3) by SDS-PAGE and Western blot. Results : Apoptosis in $MPP^+$-induced PC-12 cells was accompanied by an increased Bax/Bcl-2 ratio, release of cytochrome c to the cytosol and the activation of caspase-3. PC extract inhibited the down-regulation of Bcl-2 and the up-regulation of Bax, as well as the release of mitochondrial cytochrome c into the cytosol. In addition, PC extract attenuated caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP). Conclusion : These results suggest that the neuroprotective potentials of PC extract against $MPP^+$-induced apoptosis can be. at least partially, ascribed to its anti-apoptotic effects in PC-12 cells.