• 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.

• 대한한의학방제학회지
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• 제16권2호
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• pp.11-29
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• 2008

Objective : The aim of this study was to analyse the latest trend of medical science articles about Bojungikki-Tang published in Japan. Methods : We searched medical science articles published from 2003 to 2008 in Japan on the web site, CiNii and then these articles were reviewed and classified according to experimental subject and method. Results : Fifty-two articles, related to Bojungikki-Tang were searched and these were classified into three classes, pharmacological signaling studies, clinical case studies and the others. As a result of classification, clinical case studies were most abundant by 38 cases, pharmacological signaling studies were 10 and the others were 4. This result suggested that the study of Bojungikki-Tang was mainly focused on clinical study rather than experimental study. Among the clinical case studies, clinical studies related to immune disease took the most greatest number and number of other clinical studies were evenly distributed over the various disease. Immune intensification effect of Bojungikki-Tang can be thought continuous with reinforce the middle Jiao Qi in company with improvement effect on growth hormone failure and male infertility. A fact that the one prescription, Bojungikki-Tang could be used to treat various diseases reflects a viewpoint of Oriental medicine that is based on the respect for and understanding of individual constitution and disposition while paying attention to the gender difference and individuality. The clinical usefulness of Bojungikki-Tang on obstructive sleep apnea syndrome and visceroptosis concerns with ascend Yang and treat Qi sinking. Pharmacological signaling studies were mainly focused on diseases that were treated Bojungikki-Tang in clinic, however, there was one study that experimented on changes of numerous gene expression according to the treatment of Bojungikki-Tang using DNA array. Conclusion : The therapeutic system of Oriental medicine is different in various aspects form that of Western medicine and appropriate harmonization of east and west is expected to improve the quality of medical care. In this regard, continuous investigation and analysis about herbal medical science papers in Japan can also be useful to make progress in Korean traditional medicine.

• 대한약침학회지
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• 제24권1호
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• pp.1-13
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• 2021

Flavonoids consist a wide range of naturally occurring compounds which are exclusively found in different fruits and vegetables. These medicinal herbs have a number of favourable biological and therapeutic activities such as antioxidant, neuroprotective, renoprotective, anti-inflammatory, anti-diabetic and anti-tumor. Troxerutin, also known as vitamin P4, is a naturally occurring flavonoid which is isolated from tea, coffee and cereal grains as well as vegetables. It has a variety of valuable pharmacological and therapeutic activities including antioxidant, anti-inflammatory, anti-diabetic and anti-tumor. These pharmacological impacts have been demonstrated in in vitro and in vivo studies. Also, clinical trials have revealed the efficacy of troxerutin for management of phlebocholosis and hemorrhoidal diseases. In the present review, we focus on the therapeutic effects and biological activities of troxerutin as well as its molecular signaling pathways.

• Toxicological Research
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• 제21권3호
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• pp.195-208
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• 2005

Diabetes is a major cause of morbidity and mortality, and associated with a high risk of atherosclerosis, and liver, kidney, nerve and tissue damage. Defective insulin secretion in pancreas and/or insulin resistance in peripheral tissues is a central component of diabetes. It is well established that, regardless of the degree of muscle insulin resistance, glucose levels in diabetic and non-diabetic individuals are determined by the rate of hepatic glucose production. Moreover recently studies using liver-specific insulin receptor knockout mice show the paramount role of the liver in insulin resistance and diabetes. Insulin exerts a multifaceted and highly integrated series of actions via its intracellular signaling systems. The first major section of this review defines the major insulin-mediated signaling pathways including phosphatidylinositol 3-kinase and mitogen activated protein kinases. The second major section of the review presents a summary and evaluation of methods for determination of the role and function of signaling pathways, including methods for determination of kinase phosphorylation, the use of pharmacological inhibitors of kinase and dominant-negative kinase constructs, and the application of new RNA interference methods.

• 대한의생명과학회지
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• 제27권4호
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• pp.270-276
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• 2021

Physiological agents trigger a signaling process called "inside-out signaling" and activated platelets promote adhesion, granule release, and conformational changes of glycoprotein IIb/IIIa (αIIb/β₃). Activated αIIb/β₃ interacts with fibrinogen and initiates a second signaling step called "external signaling". These two signaling pathways can cause hemostasis or thrombosis, and thrombosis is a possible medical problem in arterial and venous vessels, and platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, modulating platelet activity is important for platelet-mediated thrombosis and cardiovascular disease. Esculetin is a coumarin-based physiologically active 6,7-dihydroxy derivative known to have pharmacological activity against obesity, diabetes, renal failure and CVD. Although some studies have confirmed the effects of esculetin in human platelet activation and experimental mouse models, it is not clear how esculetin has antiplatelet and antithrombotic effects. We confirmed the effect and mechanism of action of escultein on human platelets induced by collagen. As a result, esculetin decreased Ca²⁺ recruitment through upregulation of inositol 1, 4, 5-triphosphate receptor. In addition, esculetin upregulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-dependent pathways and inhibits fibrinogen binding and thrombus contraction. Our results demonstrate the antiplatelet effect and antithrombotic effect of esculetin in human platelets. Therefore, we suggest that esculetin could be a potential phytochemical for the prevention of thrombus-mediated CVD.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.14-21
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• 2001

Many epidemiological studies have revealed that the use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of colon cancer. Since the well-documented pharmacological action of aspirin and other NSAIDs is the inhibition of cyclooxygenase [COX, the rate-limiting enzyme in prostaglandin (PG) biosynthesis], it has been inferred that the beneficial effect of NSAIDs may be mediated through the inhibition of PG biosynthesis.(omitted)

• Journal of Ginseng Research
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• 제46권2호
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• pp.206-213
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• 2022

Ginsenoside Rb2 is an active protopanaxadiol-type saponin, widely existing in the stem and leave of ginseng. Rb2 has recently been the focus of studies for pharmaceutical properties. This paper provides an overview of the preclinical and clinical pharmacokinetics for Rb2, which exhibit poor absorption, rapid tissue distribution and slow excretion through urine. Pharmacological studies indicate a beneficial role of Rb2 in the prevention and treatment of diabetes, obesity, tumor, photoaging, virus infection and cardiovascular problems. The underlying mechanism is involved in an inhibition of oxidative stress, ROS generation, inflammation and apoptosis via regulation of various cellular signaling pathways and molecules, including AKT/SHP, MAPK, EGFR/SOX2, TGF-β1/Smad, SIRT1, GPR120/AMPK/HO-1 and NF-κB. This work would provide a new insight into the understanding and application of Rb2. However, its therapeutic effects have not been clinically evaluated. Further studies should be aimed at the clinical treatment of Rb2.

• Natural Product Sciences
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• 제19권2호
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• pp.120-126
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• 2013

Natural products have always been a pivotal source of new drug development. Dry roots of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a perennial herb and is also known as Bang Pung in traditional medicine. Numerous in vitro and in vivo studies have revealed the diverse pharmacological effects of S. divaricata and its role in the treatment of various diseases. This herb has exhibited significant inhibitory effects against inflammation and associated disorders. The present study explored the ethnopharmacological applications and molecular mechanisms behind the anti-inflammatory effects of S. divaricata herb and a single compound blockade of multi-signaling inflammatory cascades. Taken together, this review provides insight into the potential role of S. divaricata against various inflammatory diseases.

• 동의생리병리학회지
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• 제36권6호
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• pp.229-234
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• 2022

Lung cancer is the leading cause of cancer-related deaths worldwide. Indigo Naturalis (IN) is a dark blue powder obtained by processing leaves or stems of indigo plants, its anticancer effects have been reported in several studies. However, the pharmacological mechanism of IN in small cell lung cancer (SCLC) is not elucidated. In this study, to investigate the anticancer efficacy of IN for SCLC, we presented potential active ingredients, SCLC-related targets, and pharmacological mechanisms of IN that are expected to have anticancer activity for SCLC using a network pharmacological analysis. The phytochemical compounds of IN have been collected through TCMSP, SymMap, or HPLC documents. The active ingredients of IN such as indirubin, indican, isatin, and tryptanthrin were selected through ADME parameters or literature investigations for each compound. Using the Compounds, Disease-Target associations Databases, 124 common targets of IN and SCLC were obtained. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis was carried out. GO biological processes are associated with response to xenobiotic stimulus, positive regulation of protein phosphorylation, regulation of mitotic cell cycle, and regulation of apoptotic signaling pathway. KEGG disease pathways included Gastric cancer, Bladder cancer, SCLC, and Melanoma. The main anticancer targets of the IN for SCLC were analyzed in 14 targets, including BCL2, MYC, and TP53. In conclusion, the results of this study based on the network pharmacology of IN can provide important data for the effective prevention and treatment of SCLC.

• The Korean Journal of Physiology and Pharmacology
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• 제24권2호
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• pp.129-135
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• 2020

SHP2 is an unusual protein phosphatase that functions as an activator for several signaling pathways, including the RAS pathway, while most other phosphatases suppress their downstream signaling cascades. The physiological and pathophysiological roles of SHP2 have been extensively studied in the field of cancer research. Mutations in the PTPN11 gene which encodes SHP2 are also highly associated with developmental disorders, such as Noonan syndrome (NS), and cognitive deficits including learning disabilities are common among NS patients. However, the molecular and cellular mechanism by which SHP2 is involved in cognitive functions is not well understood. Recent studies using SHP2 mutant mice or pharmacological inhibitors have shown that SHP2 plays critical role in learning and memory and synaptic plasticity. Here, we review the recent studies demonstrating that SHP2 is involved in synaptic plasticity, and learning and memory, by the regulation of the expression and/or function of glutamate receptors. We suggest that each cell type may have distinct paths connecting the dots between SHP2 and glutamate receptors, and these paths may also change with aging.