• Journal of Ginseng Research
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• 제42권2호
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• pp.123-132
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• 2018

Ginseng has gained its popularity as an adaptogen since ancient days because of its triterpenoid saponins, known as ginsenosides. These triterpenoid saponins are unique and classified as protopanaxatriol and protopanaxadiol saponins based on their glycosylation patterns. They play many protective roles in humans and are under intense research as various groups continue to study their efficacy at the molecular level in various disorders. Ginsenosides Rb1 and Rg1 are the most abundant ginsenosides present in ginseng roots, and they confer the pharmacological properties of the plant, whereas ginsenoside Rg3 is abundantly present in Korean Red Ginseng preparation, which is highly known for its anticancer effects. These ginsenosides have a unique mode of action in modulating various signaling cascades and networks in different tissues. Their effect depends on the bioavailability and the physiological status of the cell. Mostly they amplify the response by stimulating phosphotidylinositol-4,5-bisphosphate 3-kinase/protein kinase B pathway, caspase-3/caspase-9-mediated apoptotic pathway, adenosine monophosphate-activated protein kinase, and nuclear factor kappa-light-chain-enhancer of activated B cells signaling. Furthermore, they trigger receptors such as estrogen receptor, glucocorticoid receptor, and N-methyl-$\text\tiny{D}$-aspartate receptor. This review critically evaluates the signaling pathways attenuated by ginsenosides Rb1, Rg1, and Rg3 in various tissues with emphasis on cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders.

• BMB Reports
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• 제51권10호
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• pp.520-525
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• 2018

Cardiovascular diseases arising from atherosclerosis are the leading causes of mortality and morbidity worldwide. Lipid-lowering agents have been developed in order to treat hypercholesterolemia, a major risk factor for atherosclerosis. However, the prevalence of cardiovascular diseases is increasing, indicating a need to identify novel therapeutic targets and develop new treatment agents. Adenosine receptors (ARs) are emerging as therapeutic targets in asthma, rheumatoid arthritis, cancer, ischemia, and inflammatory diseases. This study assessed whether LJ-1888, a selective antagonist for $A_3$ AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out ($ApoE^{-/-}$) mice who are fed a western diet. Plaque formation was significantly lower in $ApoE^{-/-}$ mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of $ApoE^{-/-}$ mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in $ApoE^{-/-}$ mice administered LJ-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that LJ-1888, a selective antagonist for $A_3$ AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia.

• Journal of Korean Dental Science
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• 제11권2호
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• pp.57-61
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• 2018

Purpose: Polydeoxyribonucleotide (PDRN), consisting of a mixture of deoxyribonucleotide polymers, has been suggested to have anti-inflammatory effects and enhance angiogenesis as an adenosine $A_{2A}$ receptor agonist. The aim of this study was to report the effectiveness of PDRN as an adjuvant therapy after surgical debridement in MRONJ (medication-related osteonecrosis of the jaw) patients. Materials and Methods: Five patients (1 male, 4 females, age 65~79 years) who were diagnosed with MRONJ stage 2 or 3 underwent surgical debridement and PDRN mucosal injection. After surgical debridement, patients were subject to daily injection with 1 ml of PDRN around the surgical wound for 14 days. Result: The patients' symptoms gradually disappeared. The surgical wound uneventfully healed, and no recurrence was observed during the follow-up period. Conclusion: Although further studies are required, the present study first describes the possibility of PDRN as a useful option for MRONJ treatment.

• 한국발생생물학회지:발생과생식
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• 제25권3호
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• pp.133-143
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• 2021

In contrast to the human lutropin receptor (hLHR) and rat LHR (rLHR), very few naturally occurring mutants in other mammalian species have been identified. The present study aimed to delineate the mechanism of signal transduction by three constitutively activating mutants (designated M410T, L469R, and D590Y) and two inactivating mutants (D383N and Y546F) of the eel LHR, known to be naturally occurring in human LHR transmembrane domains. The mutants were constructed and measured cyclic adenosine monophosphate (cAMP) accumulation via homogeneous time-resolved fluorescence assays in Chinese hamster ovary (CHO)-K1 cells. The activating mutant cells expressing eel LHR-M410T, L469R, and D590Y exhibited a 4.0-, 19.1-, and 7.8-fold increase in basal cAMP response without agonist treatment, respectively. However, inactivating mutant cells expressing D417N and Y558F did not completely impaired signal transduction. Specifically, signal transduction in the cells expressing activating mutant L469R was not occurred with a further ligand stimulation, showing that the maximal response exhibited approximately 53% of those of wild type receptor. Our results suggested that the constitutively activating mutants of the eel LHR consistently occurred without agonist treatment. These results provide important information of LHR function in fish and regulation with regard to mutations of highly conserved amino acids in glycoprotein hormone receptors.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.101-106
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• 2019

Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, $10^{-4}M$). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine $A_1$ receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an ${\alpha}_1$-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular $Ca^{2+}$ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.577-584
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• 2018

Bladder dysfunction is a common complication of diabetes mellitus (DM). However, there have been a few studies evaluating bladder smooth muscle contraction in DM in the presence of pharmacological inhibitors. In the present study, we compared the contractility of bladder smooth muscle from normal rats and DM rats. Furthermore, we utilized pharmacological inhibitors to delineate the mechanisms underlying bladder muscle differences between normal and DM rats. DM was established in 14 days after using a single injection of streptozotocin (65 mg/kg, intraperitoneal) in Sprague-Dawley rats. Bladder smooth muscle contraction was induced electrically using electrical field stimulation consisting of pulse trains at an amplitude of 40 V and pulse duration of 1 ms at frequencies of 2-10 Hz. In this study, the pharmacological inhibitors atropine (muscarinic receptor antagonist), U73122 (phospholipase C inhibitor), DPCPX (adenosine $A_1$ receptor antagonist), udenafil (PDE5 inhibitor), prazosin (${\alpha}_1$-receptor antagonist), verapamil (calcium channel blocker), and chelerythrine (protein kinase C inhibitor) were used to pretreat bladder smooth muscles. It was found that the contractility of bladder smooth muscles from DM rats was lower than that of normal rats. In addition, there were significant differences in percent change of contractility between normal and DM rats following pretreatment with prazosin, udenafil, verapamil, and U73122. In conclusion, we suggest that the decreased bladder muscle contractility in DM rats was a result of perturbations in $PLC/IP_3$-mediated intracellular $Ca^{2+}$ release and PDE5 activity.

• Archives of Pharmacal Research
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• 제29권11호
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• pp.1032-1041
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• 2006

Extracellular adenosine 5'-triphosphate (ATP) affects the function of many tissues and cells. To confirm the biological activity of ATP on human myeloid leukemic cells, F-36P and HL-60, cells were treated with a variety of concentrations of ATP. The stimulation with extracellular ATP induced the arrest of cell proliferation and cell death. from the analysis of Annexin-V staining and caspase activity by flow cytometry. The Annexin-V positive cells in both cell lines were dramatically increased following ATP stimulation. The expression of P2 purinergic receptor genes was confirmed, such as P2X1, P2X4, P2X5, P2X7 and P2Y1, P2Y2, P2Y4, P2Y5, P2Y6, P2Y11 in both leukemic cell lines. Interestingly, ATP induced intracellular calcium flux in HL-60 cells but not in F-36P cells, as determined by Fluo-3 AM staining. Cell cycle analysis revealed that ATP treatment arrested both F-36P and HL-60 cells at G1/G0. Taken together, these data showed that extracellular ATP via P2 receptor genes was involved in the cell proliferation and survival in human myeloid leukemic cells, HL-60 and F-36P cells by the induction of apoptosis and control of cell cycle. Our data suggest that treatment with extracellular nucleotides may be a novel and powerful therapeutic avenue for myeloid leukemic disease.

• 대한의생명과학회지
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• 제20권2호
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• pp.62-69
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• 2014

Previous our study demonstrated that ailanthoidol (3-deformylated 2-arylbenzo[b]furan), a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, is a novel anti-inflammatory agent. In this investigation, we examined the anti-adipogenic effect of ailanthoidol. Our data showed that ailanthoidol suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells. Treatment of the 3T3-L1 adipocytes with ailanthoidol resulted in an attenuation of the releases of leptin and interleukin-6. The expression of peroxisome proliferator-activated receptor $(PPAR){\gamma}$ and CCAAT/enhancer-binding protein $(C/EBP){\alpha}$, the central transcriptional regulators of adipogenesis, was decreased by treatment with ailanthoidol. Additionally, ailanthoidol treatment increased the phosphorylation levels of 5' adenosine monophosphate-activated protein kinase. These results suggest that ailanthoidol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$ expression. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of ailanthoidol.

• Asian-Australasian Journal of Animal Sciences
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• 제27권12호
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• pp.1783-1793
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• 2014

Capsaicin is a major constituent of hot chili peppers that influences lipid metabolism in animals. In this study, we explored the effects of capsaicin on adipogenic differentiation of bovine bone marrow mesenchymal stem cells (BMSCs) in a dose- and time-dependent manner. The BMSCs were treated with various concentrations of capsaicin (0, 0.1, 1, 5, and $10{\mu}M$) for 2, 4, and 6 days. Capsaicin suppressed fat deposition significantly during adipogenic differentiation. Peroxisome proliferator-activated receptor gamma, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer binding protein alpha, fatty acid binding protein 4, and stearoyl-CoA desaturase expression decreased after capsaicin treatment. We showed that the number of apoptotic cells increased in dose- and time-dependent manners. Furthermore, we found that capsaicin increased the expression levels of apoptotic genes, such as B-cell lymphoma 2-associated X protein and caspase 3. Overall, capsaicin inhibits fat deposition by triggering apoptosis.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.419-425
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• 1998

To clarify the effect of extracellular ATP in cultured C6 glioma cells, ATP-induced cytosolic free calcium ($[Ca^{2+}]_i$) mobilization and cell proliferation were investigated. ATP-induced $[Ca^{2+}]_i$ increased in a dose-dependent manner $(10^{-7}\;M{\sim}10^{-3}\;M)$. ATP-induced $[Ca^{2+}]_i$ increases were slightly slowed in extracellular calcium-free conditions especially in sustained phase. ATP-induced $[Ca^{2+}]_i$ increment was also inhibited by the pretreatment of U73122, a phospholipase C (PLC) inhibitor, in a time-dependent manner. Suramin, a putative $P_{2Y}$ receptor antagonist, dose-dependently weakened ATP-induced $[Ca^{2+}]_i$ mobilization. Significant increases in cell proliferation were observed at 2, 3, and 4 days after ATP was added. Stimulated cell proliferation was also observed with adenosine at days 2 and 3. This cell proliferation was significantly inhibited by the treatment with suramin. Ionomycin also stimulated cell proliferation in a concentration-dependent manner. In conclusion, we suggest that extracellular ATP stimulates C6 glioma cell proliferation via intracellular free calcium mobilization mediated by purinoceptor.