• Biomedical Science Letters
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• v.25 no.1
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• pp.92-98
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• 2019

Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

• Herbal Formula Science
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• v.25 no.4
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• pp.483-497
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• 2017

Background : Behavioral stress has been suggested as one of the significant factors that is able to disrupt physiological systems and cause depression as well as changes in various body systems. The stressful events can alter cognition, learning, memory and emotional responses, resulting in mental disorders such as depression and anxiety. Results : We used a restraint stress model to evaluate the alteration of behavior and stress-related blood parameter. The animals were randomly divided into two groups of five animals each group. Furthermore, we assessed the change of body weight to evaluate the locomotor activity as well as status of emotional and anxiety in mice. After 7 days of restraint stress, the body weight had significantly decreased in the restraint stress group compared with the control group. We also observed stress-associated behavioral alterations, as there was a significant decrease in open field and forced swim test, whereas the immobilization time was significantly increased in the stress group compared to the control group. We observed the morphological changes of neuronal death and microglia by immunohistochemistry and western blot. In our study restraint stress did not cause change in neuronal cell density in the frontal cortex and CA1 hippocampus region, but there was a trend for an increased COX-2 and iNOS protein expression and microglia (CD11b) in brain, which is restraint stress. Conclusion : Our study, there were significant alterations observed in the behavioral studies. We found that mice undergoing restraint stress changed behavior, confirming the increased expression of inflammatory factors in the brain.

• Food Science and Preservation
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• v.12 no.5
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• pp.482-488
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• 2005

Oxidant stress is well-known for a pivotal parameter related to neuro-inflammatory diseases including Alzheimer's disease, Parkinson's disease, and ALS (Lou Gehrig's disease). In order to effectively screen for anti-inflammatory agents, we first established the infrastructure of high throughput screening for anti-oxidant agents from medicinal insect library extracted with water, methanol, ethanol, and dimethyl sulfoxide. By the screening system, we found that Tenodera angustipennis Saussure, Pyrocoela rupa Olivier and Papilio maackii Mntris had strong anti-oxidant activity. Moreover, Tenodera angustipennis Saussure and Tenodera aridifolia (Stoll) exhibited protection effects of cellular damage by treatment of an oxidant hydrogen peroxide. Together, the results suggest that some selected hits could be a potential agent against neuro-inflammation, although the in vivo studies should be clearly tested.

• Molecules and Cells
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• v.45 no.3
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• pp.134-147
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• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

• Journal of Veterinary Clinics
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• v.37 no.3
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• pp.149-152
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• 2020

One-year-old male Cocker Spaniel dog was referred for the third eyelid enlargement and inflammation in the left eye (OS). It gradually swelled for 2 weeks after the cherry eye repair by conjunctival mucosa pocket procedure at a private animal clinic. Routine ophthalmic examinations including neuro-ophthalmic examination, Schirmer tear test, intraocular pressure and corneal fluorescein staining were all normal. No lesions were found on slit lamp biomicroscopy and indirect ophthalmoscopy except for third eyelid swelling in the OS. Ultrasonography revealed cystic structure within the OS nictitating membrane. Fluid from the cyst was aspirated and there were no microorganisms or neoplastic changes. Surgical intervention was performed under general anesthesia. On the day of the surgery, there was a deep corneal ulcer in the OS, which had not existed before. Ventral palpebral surface of the third eyelid was incised horizontally to the shaft of the T-shaped hyaline cartilage. And then, a full thickness of the cystic wall was incised and marsupialized. Additionally, a direct suture was performed on the ulcerated cornea. Topical and systemic antibiotics and anti-inflammatory drugs were prescribed. One month after the surgery, the third eyelid swelling and the discharge were improved. Marsupialization of the nictitating membrane cyst relieved the swelling of the third eyelid and inflammation. It could be a simple but effective surgical intervention for the cystic complication of conjunctival mucosa pocket procedure in dogs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.871-877
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• 2008

Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses and mediators of inflammation. HO-1 has been recently implicated in regulation of angiogenesis via expression of VEGF. The purpose of this study was to determine the effects of HO-1 modulation on the collagen-induced arthritis (CIA) model and on angiogenesis via up- regulation of VEGF expression in human synovial fibroblast. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 1 to day 35 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, histopathologic changes were examined on the joints. VEGF expression in paws were measured by immunohistochemical stain. mRNA expression of HO-1 and VEGF stimulated with various concentration of $TNF-{\alpha}$, CoPP accessed on human synovial fibroblast by RT-PCR. Effects of pretreatment with SnPP on mRNA expression of HO-1 and VEGF in the presence of CoPP and $TNF-{\alpha}$ in synovial fibroblast was accessed by Real-time RT-PCR. Administration of cobalt protoporphyrin IX significantly induced the inflammatory response, with increased arthritis index and expression of VEGF in the paws of the arthritis models. Treatment with SnPP significantly reduced the severity of CIA through inhibition of joint inflammation and cartilage destruction. The expression of VEGF were also significantly reduced by SnPP treatment in the paw. CoPPIX as inducer of HO-1, increased HO-1 and VEGF expression dose dependently in synovial fibroblast. In contrast, inhibition of HO-1 activity by SnPPIX abrogated CoPPIX-induced HO-1 and VEGF production in synovial fibroblast. Stimulation with $TNF-{\alpha}$ increased HO-1 and VEGF expression itself and showed additive effect on HO-1 and VEGF expression when it treated with CoPP. When SnPP was treated with CoPP and $TNF-{\alpha}$, it abrogated the CoPP induced HO-1 and VEGF expression and also abrogated $TNF-{\alpha}$ induced HO-1 and VEGF expression in synovial fibroblast. The effects of HO-1 induction in rheumatoid arthritis results in aggravation of arthritis via up-regulation of VEGF. I concluded that inhibition of the expression or activity of HO-1 could be a therapeutic target of rheumatoid arthritis.

• Journal of Pharmacopuncture
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• v.22 no.1
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• pp.16-27
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• 2019

Generative and vegetative parts of the cactuses have had a long-lasting position in folk medicine and their effects could partly be confirmed in scientific experiments. Nowadays, the cactus, fruits, and cladodes are the focus of many studies because of their desirable properties. Therefore, the summarized reports of valuable properties of medicinal plants may be a good way to familiarize researches with a new source of drugs with lower side effects and higher efficacy. Opuntia dillenii, a well-known member of the Cactaceae family, is used as a medicinal plant in various countries and grows in the desert, semi-desert, tropical and sub-tropical areas. It shows diverse pharmacological activities such as: antioxidant, anti-inflammatory, anti-tumor, neuroprotective, hepatoprotective, hypotensive etc. OD fruit also possesses valuable constitutes for instance: betalains, ascorbic acid, total phenol, protein as well as essential elements which suggest the significant potential of this plant as a complementary therapy against several pathological conditions. This review describes experimental evidence about pharmacological and therapeutic potential of OD in order to give the basis of its application in the prevention and treatment of some chronic diseases. More studies on OD can help better understanding of its pharmacological mechanism of action to explain its traditional uses and to identify its potential new therapeutic applications.

• The Korea Journal of Herbology
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• v.35 no.2
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• pp.31-38
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• 2020

Objectives : Jakyakgamcho-tang has been used as analgesic and spasmolytic for muscle pain. It has reported to anti-diabetes, anti-inflammation, and neuro-protective effects. A clinical study of muscle fatigue and pain improvement effect of Jakyakgamcho-tang has been reported with increasing frequency of clinical use. However, the anti-fatigue effect of Jakyakgamcho-tang in animal model has not been studied. In this study, we compared anti-physical fatigue effects of water and 30% ethanol extract of Jakyakgamcho-tang. Methods : The amounts of components contained in water and 30% ethanol extract of Jakyakgamcho-tang were compared by ultra-performance liquid chromatography. Anti-physical fatigue effects were evaluated using weight-loaded forced swimming test. We also investigated the effects of Jakyakgamcho-tang on the change of fatigue parameters by blood biochemical analysis. Results : The relative amount of components of Jakyakgamcho-tang were about 19-53% higher in the 30% ethanol extract than in the water extract. In the swimming test, 30% ethanol extract showed a significantly greater anti-fatigue effects than conventional water extract of Jakyakgamcho-tang. The 30% ethanol extract of Jakyakgamcho-tang improved the exhausted swimming time (54%), and serum lactate dehydrogenase (48%) and lactic acid (60%) levels compared with water extract of Jakyakgamcho-tang. Conclusions : These results showed that differences in the amounts of components by different extraction were associated with differences of anti-fatigue effect of Jakyakgamcho-tang. Thus, the 30% ethanol extraction method could be applied to dose-reducing formulations of traditional herbal medicines.

• Journal of Life Science
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• v.32 no.5
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• pp.362-367
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• 2022

Hempseed, a dehulled Cannabis fructus, has high nutraceutical potential. It has plenty of essential amino acids, vitamins, and essential polyunsaturated fatty acids, including α- and γ-linolenic acid. Increased exercise capacity, cognitive function, and ameliorative effects against hypercholesterolemia, neuro-inflammation, thrombus formation, and learning and memory impairment were reported in hemp-seed oil-administered models. Therefore, the market prices of hempseed oil are 45~140-fold higher than the other plant-derived oils, such as soy, corn, olive, canola, or linseed oil. In this study, instead of FTIR (Fourier Transform Infrared Spectroscopy) or FTIR-Raman spectroscopy, a simple UV-Vis spectrophotometry method was developed to authenticate the hempseed oil. Measurements of absorbance at 245, 305, and 415 nm of oils and calculations of 245/415 and 315/415 nm provided that the ratios of 245/415 and 315/415 nm of authentic hempseed oils were 12.9 and 9.6, respectively. The 245/415 and 315/415 nm of soy oil, corn oil, canola oil, and linseed oil were 35.4~61.8 and 29.7~50.8, respectively. This simple UV-Vis spectrophotometry method could also be applied to differentiate hempseed oil from blended oil products in markets.