• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.313-321
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• 1995

Conflicting data have been reported on the effect of nicotine on gastric mucosal damage. To elucidate the effect of chronic intermittent nicotine on gastric mucosal damage, intragastric nicotine (5 mg/kg, 10 mg/kg) was administered twice per day for 9 days. Gastric mucosal damage was created by s.c. injection of a large dose (1.2 mg/kg) of pentagastrin followed by pylorus ligation for 6 hours. Nicotine treated rats showed reduced gastric mucosal damage about 50% of the control. To examine the mechanism of the protective effect of nicotine, gastric perfusion experiments were done. Basal acid secretion was not affected by intragastric or intravenous nicotine. However, pentagastrin-stimulated acid secretion markedly inhibited by a bolus injection of nicotine, and this response was dose-related. These data indicates that chronic intermittent administration of nicotine protects gastric mucosa against gastrin-induced gastric mucosal damage, and nicotine-induced inhibition of gastrin-stimulated acid secretion has an important role for the protective effect of nicotine. Considering reports concerning nicotine's aggravating effect on the gastric mucosal damage, it is suggested that the methods of administration of nicotine may be an important decisive factor of the divergent action of nicotine on the gastric mucosa.

• The Journal of Internal Korean Medicine
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• v.41 no.1
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• pp.1-13
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• 2020

Objectives: Osteoarthritis (OA) is a chronic and degenerative joint disease characterized by progressive degeneration of articular cartilage. Inflammation is a recognized and important factor of OA progression. The present study was designed to investigate the protective effect of Corni Fructus water extract (CFW) on a monosodium iodoacetate (MIA)-induced rat model of OA. Methods: Osteoarthritis was induced by injection of MIA (50 µL; 80 mg/mL) into the knee joint cavity of rats. After an adaptation period for seven days, the rats were divided into 4 groups (n=8/group): normal, control, indomethacin-treated (5 mg/kg), and CFW-treated (200 mg/kg) groups. The rats were treated orally for 14 days. Pain was evaluated by determining hind paw weight distribution. For biochemical analyses, we measured the changes in reactive oxygen species (ROS) and peroxynitrite (ONOO^-) in the knee joint. The presence of anti-oxidant proteins and inflammatory proteins was determined by western blotting. Results: The administration of CFW significantly improved the hind paw weight distribution. The ROS and ONOO^- levels of knee joint were significantly decreased in the CFW group. CFW inhibited the production of inflammatory mediators, such as COX-2, and inflammatory cytokines, including IL-6 and IL-1β, via the NF-κB signaling pathway. The expression of anti-oxidant enzymes, such as catalase and GPx-1/2 also increased significantly. Conclusions: The findings indicate that CFW has a therapeutic and protective effect on OA by suppression of inflammation. Therefore, CFW could represent a potential and effective candidate for OA treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.394-402
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• 2003

This study was designed to investigate the protective effect of Bojungmyunyuk-dan(BJMY-Dan) on the cisplatin-induced cytotoxicity of primary rat astrocytes. BJMY-Dan is an oriental herbal prescription for its ability to recover protective effects against anti-cancer chemotherapies. After astrocytes were treated cisplatin, MTT assay was performed for cell viability test. To explore the mechanism of cytotoxicity, I used the several measures of apoptosis to determine whether this processes was involved in cisplatin-induced cell damage in astrocytes. Also, astrocytes were treated with BJMY-Dan and then, followed by the addition of cisplatin. Cisplatin decreased the viability of astrocytes in a dose and time-dependent manner. BJMY-Dan increased the viability of astrocytes treated cisplatin. Astrocytes treated cisplatin were revealed as apoptosis characterized by nuclear staining and flow cytometry. BJMY-Dan protected astrocytes from cisplatin-induced nuclear fragmentation and chromatin condensation. Also, caspase-3 and caspase-9 proteases were activated in astrocytes by cisplatin. BJMY-Dan inhibited the activation of caspase proteases in cisplatin-treated astrocytes. Cleavage of [poly(ADP-ribose) polymerase](PARP) was occurred at 12hr after treatment of cisplatin in astrocytes. BJMY-Dan recovered the cleavage of PARP in cisplatin-treated astrocytes. Also, BJMY-Dan inhibited the activation of pro-apoptotic factor, Bak by cisplatin. Lastly, astrocytes stained with JC-1 and Rhodamine 123 were photographed by fluorescence microscope to visualize changes of mitochondrial membrane permeability transition(MPT) during treatment with cisplatin for 24hr. BJMY-Dan recovered the change of MPT by cisplatin in astrocytes. According to above results, BJMY-Dan may protect astrocytes from cytotoxicity induced by chemotherapeutic agents, including cisplatin.

• Journal of Life Science
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• v.25 no.5
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• pp.539-547
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• 2015

This study aimed to investigate the protective effect of Semisulcospira libertina extract on liver injury induced by D-galactosamine in rats. After the administration of S. libertina extract, the local fat degeneration and infiltration of inflammatory cells in liver tissues were significantly decreased and peripheral hemorrhages around portal triads and central necrosis around central veins were found to be protective. The elevated levels of plasma ALT, AST, and LDH, the ALP activation lipid peroxidation, and the lipid contents of a damaged liver were recovered in experimental rats administrated with S. libertina extract, suggesting its role in blood enzyme activation and lipid content restoration within damaged rat liver tissues. Moreover, the expression rate of TNF-α, which accelerates inflammation and induces tissue damage and necrosis, was significantly decreased. In addition, the activities of antioxidant enzymes were more effectively upregulated compared to those of the control group induced hepatotoxicity. All data showed that S. libertina extract has a preventive role against liver damages, such as inflammation and tissue necrosis, as instigated with D-galactosamine by improving the activities of blood enzymes and antioxidant enzymes and modulating the expression of inflammation factor, suggest S. libertina extract is an effective medicinal resource for the restoration of hepatotoxicity.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.693-704
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• 2021

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

• The Korea Journal of Herbology
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• v.36 no.6
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• pp.1-8
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• 2021

Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

• The Korea Journal of Herbology
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• v.38 no.1
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• pp.11-19
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• 2023

Objectives : Neuroinflammation is a common pathological mechanism of neurodegenerative diseases, and the development of therapeutic agents is urgently needed. Red ginseng has been known to be good for the immune stimulation in Eastern Asia. Although the immuno-stimulatory activity of red ginseng are already known, the neuro-protective effects of cultivated red ginseng with fermented complex mushroom-cereal mycelium (RGFM) have not been conducted. Thus, in this study, we tried to investigate the anti-neuroinflammatory effect of RGFM water extract on lipopolysaccharide (LPS) stimulated BV2 cells. Methods : BV2 cells were pretreated with RGFM 1 h prior to LPS exposure. To determine the neuro-protective effects of RGFM water extract, we measured the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and nitric oxide (NO) and pro-inflammatory cytokines such as interleukin (IL)-1𝛽, IL-6 and tumor necrosis factor (TNF)-𝛼 in LPS-stimulated BV2 cells. In addition, to find out the regulatory mechanism of RGFM water extract, we assessed the protein levels of mitogen-activated protein kinases (MAPKs) and inhibitory 𝜅B𝛼 (I𝜅B𝛼) by western blotting. Results : In our study, treatment of RGFM reduced the mRNA expression of iNOS and COX-2 and suppressed NO production in LPS-stimulated BV2 cells. Additionally, the secretion of IL-1𝛽 and TNF-𝛼 but not IL-6 was significantly inhibited by RGFM. Furthermore, RGFM water extract inhibited the phosphorylation of c-Jun N-terminal kinase (JNK). Conclusions : Taken together, these findings suggest that RGFM water extract has a protective effect on neuroinflammation through inhibition of JNK.

• The Korea Journal of Herbology
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• v.34 no.1
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• pp.75-80
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• 2019

Objectives : Dictamni Radicis Cortex (DRC) has been used as an important traditional medicine for inflammation and fungal diseases. However, the protective effect of DRC water extract on acute pancreatitis (AP) has not been deeply reported. Therefore, we aimed to evaluate the protective effects of DRC water extract on cerulein-induced AP. Methods : AP was induced via intraperitoneal injection of supramaximal concentrations of stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) every hour for 6 times. DRC water extract (0.05, 0.1, or 0.2 g/kg) or saline was administrated intraperitoneally 1 h before to the first injection of cerulein. The mice were sacrificed at 6 h after the final cerulein injection. Pancreas was rapidly removed for histochemical examination and myeloperoxidase (MPO) assay. In addition, polymerase chain reaction (PCR) was performed to examine mRNA levels of proinflammatory cytokines such as Interleukin $(IL)-1{\beta}$, IL-6 and Tumor necrosis factor $(TNF)-{\alpha}$. Results : Administration of DRC water extract significantly inhibited the pancreatic weight to body weight ratio, pancreas histological damages and increase of pancreatic MPO activity during cerulein-induced AP. In addition, increased pancreatic mRNA levels of $IL-1{\beta}$, IL-6 but not $TNF-{\alpha}$ were significantly inhibited by treatment of DRC water extract against cerulein-induced AP. Conclusions : In conclusion, we have revealed that pre-treatment of DRC water extract reduces the severity of cerulein-induced AP. Accordingly, our results could give a clinical basis that DRC could be used as a drug or agent to prevent AP.

• Food Science and Preservation
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• v.23 no.3
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• pp.378-386
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• 2016

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.547-558
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majorities of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to hoot. In previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF. Understanding the mechanisms of TNF-resistance in TNF-$\alpha$ gene transfected cancer cells would be an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of new protective protein synthesis in the acquired resistance to TNF of TNF-$\alpha$ gene transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164, a murine fibrosarcoma cell line, using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF gene transfected cells(WEHI164-TNF) and the changes of TNF sensitivities after treatments with actinomycin D(transcription inhibitor) and cycloheximide ( translation inhibitor). Results : WEHI164 which was sensitive to TNF became resistant to TNF after being transfected with TNF-$\alpha$ gene and the resistance to TNF was partially reversed after treatment with actinomycin D, but not with cycloheximide. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ gene transfection may be associated with synthesis of some protective proteins.