• Archives of Pharmacal Research
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• v.25 no.6
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• pp.923-931
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• 2002

Sopungsungi-won (SP) is a known for\mula for senile constipation and diabetes mellitus, based on traditional Korean medicine. The preventive effect of SP on the development of overt diabetes in Zucker diabetic fatty (ZDF) rats was evaluated. When administered orally through a diet for 8 weeks, diabetic conditions such as hyperglycemia, polydipsia and hypertriglyceridemia were all ameliorated in SP-treated rats. In parallel with the onset and progression of hyperglycemia in the ZDF control rats; there was a marked decline in plasma insulin concentrations from 26.1 $\mu$U/ml, at age 7 weeks, to 14.8 $\mu$U/ml at age 15 weeks. In the SP-treated rats, however, the plasma insulin concentrations did not decline, and SP at a dose of 5 g/kg significantly increased the insulin levels to 31.9 $\mu$U/ml. Early normalization of plasma insulin and a retained ability to subsequently increase plasma insulin were indicative of a pancreatic $\beta$ cell protective action by the SP for\mula. In addition, expressions of an insulin-responsive gene and corresponding protein, glucose transporter 4 (GLUT4), in skeletal \muscle, were also determined in SP- and rosiglitazone-treated ZDF rats. mRNA and protein levels of GLUT4 in SP-treated rats were upregulated in a dose dependent manner. Furthermore, when ZDF rats were treated with 2 g/kg of the SP for\mula, the activity of glucose-6-phosphatase was decreased by 49%, whereas the activity of glucokinase was increased by 196%, compared to the ZDF control rats. Taken together, these data provide evidence that the SP for\mula markedly lowered the plasma glucose levels, probably through an effect not only on improvement of insulin action, but through a combined sti\mulation of glycolysis and an inhibition of gluconeogenesis in the liver, and also suggest the validity of SP's clinical use in the treatment of type 2 diabetes mellitus following further toxicological investigation.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.6
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• pp.281-286
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• 2002

To understand the cytotoxic mechanism of $MPP^+,$ we examined the involvement of ceramide in $MPP^+-induced$ cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to $MPP^+,\;MPP^+$ induced dose-dependent cytotoxicity accompanied by 2-fold elevation of intracellular ceramide levels in SH-SY5Y cells. Three methods were used to test the hypothesis that the elevated intracellular ceramide is related to $MPP^+-induced$ cytotoxicity: $C_2-ceramide$ was directly applied to cells, sphingomyelinase (SMase) was exogenously added, and oleoylethanolamine (OE) was used to inhibit degradation of ceramide. Furthermore, inhibition of ceramide-activated protein phosphatase (CAPP), the effector of ceramide, using okadaic acid (OA) attenuated cell death but treatment of fumonisin $B_1,$ the ceramide synthase inhibitor, did not alter the cytotoxic effect of $MPP^+.$ Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in $MPP^+-induced$ cell death.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2487-2490
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• 2013

SA51, a medium potency inhibitor of protein tyrosine phosphatase 1B (PTP1B), was identified to be a potent inhibitor of $I{\kappa}B$ kinase ${\beta}$ ($IKK{\beta}$). Consistent with this, SA51 prevented lipopolysaccharide (LPS)-induced breakdown of $I{\kappa}B{\alpha}$ in macrophages. The effects of SA51 in mice were compared with those of structurally related compounds, SA18 and SA32, which were previously reported as inhibitors of both enzymes - less potent against $IKK{\beta}$ but more potent against PTP1B compared to SA51. SA51 improved glucose tolerance and lipid parameters in mice, consistent with the results reported for $IKK{\beta}^{+/-}$ mice. In contrast, SA18 and SA32 showed anti-obesity effects without anti-diabetic effects. Collectively, the effects of SA51 could be due largely to the inhibition of $IKK{\beta}$, whereas SA18 and SA32 may be more likely to inhibit PTP1B, consistent with their relative in vitro inhibitory effects.

• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.11-20
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• 2019

Ecklonia cava, an edible marine brown alga (Laminariaceae), is a rich source of bioactive compounds such as fucoidan and phlorotannins. Ecklonia cava extract (ECE) was prepared using 70% ethanol extraction and ECE contained 67% and 10.6% of total phlorotannins and dieckol, respectively. ECE treatment significantly inhibited receptor activator of nuclear $factor-{\kappa}B$ ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells and pit formation in bone resorption assay (p <0.05). Moreover, it suppressed RANKL-induced $NF-{\kappa}B$ and mitogen-activated protein kinase signaling in a dose dependent manner. Downregulated osteoclast-specific gene (tartrate-resistant acid phosphatase, cathepsin K, and matrix metalloproteinase-9) expression and osteoclast proliferative transcriptional factors (nuclear factor of activated T cells-1 and c-fos) confirmed ECE-mediated suppression of osteoclastogenesis. ECE treatment ($100{\mu}g/ml$) increased heme oxygenase-1 expression by 2.5-fold and decreased intercellular reactive oxygen species production during osteoclastogenesis. The effective inhibition of RANKL-stimulated osteoclast differentiation and oxidative stress by ECE suggest that ECE has therapeutic potential in alleviating osteoclast-associated disorders.

• Journal of Society of Preventive Korean Medicine
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• v.10 no.2
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• pp.19-30
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• 2006

It is well known that glucocorticoid may induce osteoporosis as its side effect in long-term therapy. The inhibition of osteoblast by glucocorticoid is also recognized as its action mechanism of decreased bone formation. In this study, the effect of DSG, Danchisoyosangamibang, on the differentiation and function of osteoblastic cells was investigated. The osteoblastic cells were isolated from rat calvariae using collagenase treatment. The cell counting, enzyme activity assay, MTT assay, collagen content assay were done to determine the cell proliferation, intracellular alkaline phosphatase (ALP) activity, bone martrix production, and cell apoptosis. DSG enhanced the cell proliferation after the culture for 10 days. ALP activity and total protein synthesis, and intracelluar collagen synthesis were increased time dependently when the cells were treated with DSG in the presence of dexamethasone. And, DSG restored calvarial cell function decreased by dexamethasone.

• Advances in Traditional Medicine
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• v.7 no.3
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• pp.304-310
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• 2007

Monocrotophos was administered orally to adult male albino mice at dose level of 3.0 mg/kg body weight/day/mice for 50 days. The treatment has found to affect spermatogenesis as well as the endocrine functions of the testis as indicated by gravimetric, histopathological and biochemical changes. The treatment has caused degenerative changes in the seminiferous tubules and Leydig cells of the testis and regression of the epididymis, seminal vesicle, vas deferens, prostate, Cowper's gland and levator ani. Similarly, cauda epididymal sperm count and sperm motility have shown significant reduction. There was a significant reduction in the protein, glycogen, sialic acid, acid and alkaline phosphatase and increase in cholesterol in the testis of monocrotophos treated mice compared with the control. The causative factors for these changes due to monocrotophos administration were discussed.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.2
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• pp.197-206
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• 2008

The inhibition of osteoblast by glucocorticoid is recognized as its action mechanism of decreased bone formation. In this study, the effect of JY, Jahyulyangkeuntang, on the differentiation and mineralization of osteoblastic cells was investigated in the presence of dexamethasone. The cell counting, enzyme activity assay, MTT assay, collagen content assay were done to determine the cell proliferation, alkaline phosphatase(ALP) activity, bone martrix production, and cell apoptosis. JY enhanced the cell proliferation after the culture for 10 days. ALP activity and total protein synthesis, and intracellular collagen synthesis were increased when the cells were treated with JY. And JY restored calvarial cell function decreased by dexamethasone.

• BMB Reports
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• v.52 no.2
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• pp.111-112
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• 2019

Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

• Natural Product Sciences
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• v.14 no.2
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• pp.113-117
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• 2008

Saururus chinensis is a commonly used folk herb for the treatment of edema and liver diseases in Korea. To study the biological activity of Saururus chinensis in bone metabolism, we evaluated the effect of its extracts on osteoclast differentiation in vitro using primary mouse bone marrow-derived macrophages. Methanol extract (ME) from dried roots of Saururus chinensis was partitioned into methylene chloride (MF), ethyl acetate (EF), n-butanol (BF) and water fractions (WF). Tartrate-resistance acid phosphatase (TRAP) activity assay and western blot analysis were performed to determine the effect on osteoclast differentiation and mitogen-activated protein (MAP) kinases activation. ME, MF and EF dramatically inhibited receptor activator of ${NF-kB}$ ligand (RANKL)-induced formation of multinucleated osteoclasts and activation of MAP kinases. This study firstly demonstrated that ME, MF and EF of Saururus chinensis have the potential to inhibit the osteoclast differentiation, which results from the inhibition of MAP kinases activations in part.

• The Journal of Korean Obstetrics and Gynecology
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• v.29 no.2
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• pp.66-82
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• 2016

Objectives : This study was conducted to evaluate the effect of Kanghwalsokdan-tang Gamibang water extract (KSG) on osteoporosis. Methods : RANKL-stimulated RAW 264.7 was used to evaluate inhibitory effect of KSG osteoclast differentiation and gene expression. We counted TRAP (+) multinucleated cells and measured TRAP activity and mRNA expressions of osteoclastogenesis-related genes (NFATc1, MITF, JNK1, cathepsin K, MMP-9) to figure out the effect of KSG on osteoclast. Osteoblastogenesis was also determined in rat calvarial cell. Alkaline phosphatase (ALP) activity, bone matrix protein and collagen synthesis were measured by using murine calvarial cell. Results : KSG inhibited the differentiation of osteoclast precursor cell and expression of genes related osteoclastogenesis like NAFTc1, MITF, c-fos, JNK1, Cathepsin K, MMP-9 and TRAP. KSG increased cell division and function of osteoblast separated from the skull of a rat and ALP synthesis, biosynthesis of bone matrix protein and collagen. Conclusions : Reviewing these results, KSG has efficacy on osteoclast inhibition and osteoblast activation. After further study, KSG will be able to apply for osteoporosis treatment and prevention.