• The Korean Journal of Physiology and Pharmacology
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• 제28권4호
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• pp.345-359
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• 2024

Deposition of extracellular matrix (ECM) in the trabecular meshwork (TM) increases aqueous humour outflow resistance leading to elevation of intraocular pressure (IOP) in primary open-angle glaucoma, which remains the only modifiable risk factor. Resveratrol has been shown to counteract the steroid-induced increase in IOP and increase the TM expression of ECM proteolytic enzymes; however, its effects on the deposition of ECM components by TM and its associated pathways, such as TGF-β-SMAD signalling remain uncertain. This study, therefore, explored the effects of trans-resveratrol on the expression of ECM components, SMAD signalling molecules, plasminogen activator inhibitor-1 and tissue plasminogen activator in dexamethasone-treated human TM cells (HTMCs). We also studied the nature of molecular interaction of trans-resveratrol with SMAD4 domains using ensemble docking. Treatment of HTMCs with 12.5 µM trans-resveratrol downregulated the dexamethasone-induced increase in collagen, fibronectin and α-smooth muscle actin at gene and protein levels through downregulation of TGF-β1, SMAD4, and upregulation of SMAD7. Downregulation of TGF-β1 signalling by trans-resveratrol could be attributed to its effect on the transcriptional activity due to high affinity for the MH2 domain of SMAD4. These effects may contribute to resveratrol's IOP-lowering properties by reducing ECM deposition and enhancing aqueous humour outflow in the TM.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10245-10250
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• 2015

Background: Glucocorticoids are commonly co-administered with chemotherapy to prevent drug-induced allergic reactions, nausea, and vomiting, and have anti-tumor functions clinically; however, the distinct effects of GC on subtypes of tumor cells, especially in breast cancer cells, are still not well understood. In this study, we aimed to clarify the effect of GC on subtypes of T47D breast cancer cells by focusing on apoptosis, cell organization and migration, and underluing molecular mechanisms. Materials and Methods: The cell scratch test was performed to observe the cell migration rate in T47D cells treated with dexamethasone (Dex). Hoechst and MTT assays were conducted to detect cell survival and rhodamine-labeled phalloidin staining to observe cytoskeleton dynamics. Related factors in the AKT/mTOR pathway were determined by Western blotting. Results: Dex treatment could effectively inhibit T47D breast cancer cell migration with disruption of the cytoskeletal dynamic organization. Moreover, the effect of Dex on cell migration and cytoskeleton may be mediated by AKT/mTOR/RhoA pathway. Although Dex inhibited T47D cell migration, it alone may not induce cell apoptosis in T47D cells. Conclusions: Dex in T47D human breast cancer cells could effectively inhibit cell migration by disrupting the cytoskeletal dynamic organization, which may be mediated by the AKT/mTOR/RhoA pathway. Our work suggests that glucocorticoid/Dex clinical use may prove helpful for the treatment of breast cancer metastasis.

• 대한임상독성학회지
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• 제6권2호
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• pp.130-133
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• 2008

In South Korea, attempted suicide by paraquat (PQ) intoxication is fairly common, and is lethal by pulmonary fibrosis and hypoxemia. However, the treatment of PQ poisoning is primarily supportive management. To increase the survival rate associated with PQ intoxication, many treatments have been developed. Here, we treated a case of PQ intoxication with steroid pulse therapy. A 23-year-old man was admitted to the hospital because of PQ intoxication. He drank two mouthfuls of Gramoxon (24% commercial paraquat). His vital signs were stable, but he had a throat infection, and navy blue urine in the sodium dithionite test. Standard treatment, including gastric lavage with activated charcoal was performed, and emergent hemoperfusion with a charcoal filter was initiated 11 h after PQ ingestion. Pharmacotherapy was initiated 18 h after PQ ingestion with the administration of 5 mg dexamethasone. On day 10, chest PA showed pulmonary fibrosis. Therefore, we initiated steroid pulse therapy, with 1g methylprednisolone in 100 mL of D5W administered over 1 h repeated daily for 3 days, and 1 g cyclophosphamide in 100 mL of D5W administered over 1 h daily for 2 days. On day 15, dexamethasone therapy was initiated. On day 30, pulmonary fibrosis was improved. Thus, if pulmonary fibrosis becomes exacerbated after dexamethasone therapy during the subacute stage, pulse therapy with methylprednisolone and cyclophosphamide could be helpful.

• Journal of Veterinary Science
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• 제23권5호
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• pp.76.1-76.14
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• 2022

Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca²⁺/P⁵⁺ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions: DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

• 셀메드
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• 제3권3호
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• pp.24.1-24.5
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• 2013

Pharmacopuncture, or herbal acupuncture, is a new form of therapy derived from combinations of two traditional therapeutic methods, herbal medicine and acupuncture therapy. To compare the efficacy between dexamethasone-pharmacopuncture (DP) and dexamethasone-oral administration (DO), the effect of DP was investigated in murine models. Anti-anaphylactic effects of dexamethasone treatments were investigated in compound 48/80-induced systemic anaphylactic reaction, ear swelling response, and passive cutaneous anaphylaxis (PCA). DP treatment significantly inhibited the compound 48/80-induced systemic anaphylactic reaction, ear swelling response, and PCA. The effects between DP and DO were on a similar level. These results indicate that DP can be used as an alternative method for DO in case of emergency.

• 한방재활의학과학회지
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• 제23권3호
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• pp.1-14
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• 2013

Objectives The object of this study was to observe the favorable anti-arthritic effects of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) on Freund's complete adjuvant (FCA)-induced arthritic Wistar rats. Methods Rheumatoid arthritis was induced by intradermal injection of FCA, and 300, 150 or 750 mg/kg of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) were orally administered once a day for 14 days from 14 days after FCA treatments, and 15 mg/kg of dexamethasone was intraperitoneally administered as reference drug in this experiment. All rats were sacrificed at 14 days after continuous oral treatment of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) or intraperitoneal administration of dexamethasone, and changes on the body weight, knee circumferences, gross arthritis score, inflammatory tissue prostaglandin (PG) $E_2$ levels were monitored with cartilage collagen components and glucosaminoglycans compositions - chondroitin sulphate, heparan sulphate and hyaluronic acid in the present study. Results As results of FCA treatment, classic rheumatoid arthritis featuring dramatical decreases on the body weights, cartilage collagen contents and bone glucosaminoglycans-chondroitin sulphate, heparan sulphate and hyaluronic acid contents, with increases on the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels. However, these changes from FCA-induced rheumatoid arthritis were clearly reduced by treatment of dexamethasone and both two different dosages of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 and 150 mg/kg in the present study. Although FCA-induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg as compared with Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats, and Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg showed similar preserve effects on the cartilage glucosaminoglycan compositions in this study. Conclusions The results obtained in this study suggest that over 300 and 150 mg/kg of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) showed favorable anti-arthritic effects on the FCA-induced arthritis mediated by suppression of $PGE_2$, a inflammatory mediator. However, detail mechanism studies should be conduced in future with the screening of the biological active compounds in this herb. Although overall anti-inflammatory effects Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg were lowered than those of dexamethasone 15 mg/kg treated rats, Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg treated rats showed similar preserve effects on the cartilage glucosaminoglycan compositions in this experiment.

• BMB Reports
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• 제45권1호
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• pp.51-56
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• 2012

The purpose of this study was to determine the effects of duration and timing of glucocorticoid treatment on the expansion and differentiation of porcine neonatal pancreas cell clusters (NPCCs) into ${\beta}$-cells. After transplantation of NPCCs, the ductal cyst area and ${\beta}$-cell mass in the grafts both showed positive and negative correlations with duration of dexamethasone (Dx) treatment. Pdx-1 and HNF-3${\beta}$ gene expression was significantly downregulated following Dx treatment, whereas PGC-1${\alpha}$ expression increased. Pancreatic duct cell apoptosis significantly increased following Dx treatment, whereas proliferation did not change. Altogether, transdifferentiation of porcine NPCCs into ${\beta}$-cells was influenced by the duration of Dx treatment, which might have been due to the suppression of key pancreatic transcription factors. PGC-1${\alpha}$ plays an important role in the expansion and transdifferentiation of porcine NPCCs, and the initial 2 weeks following transplantation of porcine NPCCs is a critical period in determining the final ${\beta}$-cell mass in grafts.

• 동의생리병리학회지
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• 제21권1호
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• pp.86-92
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• 2007

Hibiscus sabdariffa L., a tropical beverage material, is used commonly as in folk medicine against hypertension, pyrexia, inflammation, liver disorders, and obesity. However, the mechanism by which Hibiscus sabdariffa L. modulates adipogenic differentiation is remained to be elusive. This report was designed to investigate the inhibitory effect of Hibiscus extract on insulin signaling pathway during adipocyte differentiation in 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were differentiated with isobutylmethylxanthine, dexamethasone, and insulin (MDI) and followed by the addition of Hibiscus extract. Treatment with Hibiscus resulted in a decrease of lipid droplet accumulation, which was suppressed by PI-3 kinase inhibitor wortmannin in 3T3-L1 preadipocytes. Also, Hibiscus extract markedly attenuated the mRNA expression of adipogenic transcriptional factor PPAR${\gamma}$ and adipogenic hormon Leptin during adipogenesis. However, it did not affect the expression of adiponectin in 3T3-L1 preadipocytes differentiated with MDI mixture. Furthermore, Adipogenic differentiation by MDI mixture increased the phosphorylation and expression of PI3-Kinase and Akt in 3T3 preadipocytes, which was markedly suppressed by Hibiscus extract treatment. Taken together, our results suggest that Hibiscus extract suppressed the adipogenic differentiation of 3T3 preadipocytes through activation of PI3-Kinase and Akt signaling pathway.

• The Korean Journal of Pain
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• 제2권1호
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• pp.26-29
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• 1989

Thirteen patients with various musculoskeletal inflammatory conditions and 2 postherpetic neuralgia patients received transcutaneous iontophoresis with dexamethasone sodium phosphate (1 ml = 4 mg) and 4% lidocaine hydrochloride (2 ml=80 mg, direct current 4 mA, 20 min.). Seven patients showed excellent pain relief, 4 patients showed good pain relief, and the rest of the patients had fair or poor pain relief. No side effects were seen but skin irritation and painless electrical bum were common. Results of the study indicate that iontophoresis is an effective treatment of inflammed tissues which guarantees a painless, safe and sterile method.

• Journal of Ginseng Research
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• 제48권3호
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• pp.310-322
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• 2024

Background: Osteosarcopenia is a common condition characterized by the loss of both bone and muscle mass, which can lead to an increased risk of fractures and disability in older adults. The study aimed to elucidate the response of various mouse strains to treatment with Rg3, one of the leading ginsenosides, on musculoskeletal traits and immune function, and their correlation. Methods: Six Collaborative Cross (CC) founder strains induced muscle atrophy and bone loss with dexamethasone (15 mg/kg) treatment for 1 month, and half of the mice for each strain were orally administered Rg3 (20 mg/kg). Different responses were observed depending on genetic background and Rg3 treatment. Results: Rg3 significantly increased grip strength, running performance, and expression of muscle and bone health-related genes in a two-way analysis of variance considering the genetic backgrounds and Rg3 treatment. Significant improvements in grip strength, running performance, bone area, and muscle mass, and the increased gene expression were observed in specific strains of PWK/PhJ. For traits related to muscle, bone, and immune functions, significant correlations between traits were confirmed following Rg3 administration compared with control mice. The phenotyping analysis was compiled into a public web resource called Rg3-OsteoSarco. Conclusion: This highlights the complex interplay between genetic determinants, pathogenesis of muscle atrophy and bone loss, and phytochemical bioactivity and the need to move away from single inbred mouse models to improve their translatability to genetically diverse humans. Rg3-OsteoSarco highlights the use of CC founder strains as a valuable tool in the field of personalized nutrition.