• Journal of Digital Convergence
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• v.20 no.2
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• pp.311-316
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• 2022

Tertomotide is a peptide fragment of hTert and developed as a vaccine targeting cancer. It has been reportedly known to ameliorate inflammatory symptoms in clinical tests and in animal studies. However, the therapeutic potential of tertomotide is not supposed to be comparable to conventional anti-inflammatory agents due to low druglikeness In order to treat inflammations present in varous lesion, the structure of tertomotide is required to be modified. In this context, 12 octapeptides were designed based on tertomotide and screened for the anti-inflammatory activity in activated monocyte by measuring TNF-α secretion. As a result, some octapeptides has been exerted anti-inflammatory activity, comparable to or better than tertomotide and estradiol, known anti-inflammatory agents. This result is supposed to be helpful for developing therapeutic purpose exploiting other tertomotide-derived peptides and would be an example for designing novel drug based on active biomolecules with undesirable structure by convergence study of biology and computer-aided medicinal chemistry.

• The Korea Journal of Herbology
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• v.36 no.1
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• pp.67-76
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• 2021

Objective : Yukgunja-tang is one of the herbal prescriptions widely used for functional indigestion. In this study, we evaluated the pharmacological effect through the Yukgunja-tang formulation development. Methods : The RAW 264.7 cells were pretreated with Yukgunja-tang tablet (YGJT-T : 50, 100 and 200 ㎍/㎖) and then stimulated with lipopolysaccharide (LPS : 500 ng/㎖). Cell viability, inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were measured. Also, ICR mice induced acute gastritis by oral administration of 150 mM HCl in 60% ethanol. The YGJT-T (30 mg/kg) was pretreated for 3 days, and 150 mM HCl in 60% ethanol was orally administered 1 hour after the last drug treatment. Mice were sacrificed 1 hour after oral administration of 150 mM HCl in 60% ethanol. The gastric mucosa was observed, and inflammatory cytokines in the gastric tissue were measured. Results : The marker components of YGJT-T were determined by simultaneous analysis using HPLC. In RAW 264.7 cells, pretreatment of YGJT-T was non-toxic and inhibited the production of inflammatory mediators such as NO and PGE2 and suppressed inflammatory cytokines. In addition, pretreatment of YGJT-T improved bleeding and edema due to gastric lesions caused by acute gastritis and suppressed inflammatory cytokines. Conclusion : In summary, our results confirmed that treatment with YGJT-T has anti-inflammatory and anti-gastritis effects in vitro and in vivo. Therefore, in this study, YGJT-T could support a potential strategy for the prevention and treatment of gastritis.

• The Journal of Korean Physical Therapy
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• v.14 no.4
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• pp.147-162
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• 2002

Transdermal permeation enhancer has been used to increased skin absorption. External control of drug release and skin absorption can also be achieved by iontophoresis or phonophoresis. However, because several problems with iontophoresis are that it has a risk to skin damage because of the change of pH and the increase of current density in applying it and that it can be applied only in the form of water solution, This study is to enhance drug permeation via skin following application of ultrasound. For this goal, in gel containing piroxicam, the degree of skin permeation in vitro and anti-inflammatory effect in in vivo were investigated. Permeation study using hairless mouse skin was performed at 37 $^{\circ}C$ using buffer saline as the receptor solution. The amount of piroxicam were quantified using a HPLC system consisting of solvent delivery system. Following adoption of ultrasound 1 MHZ, it showed relatively high permeation rate where it was compared with non treated by ultrasound. The influence of duty cycle having an effect on skin permeation rate was slight higher in the case of using pulsed mode. Skin permeation increase attended by intensity of ultrasound, the permeation of trice was accelerated at 2.0 W/$cm^{2}$ than 1.0 W/$cm^{2}$. The skin permeation of piroxicam was substantially influenced by ultrasound. Anti-inflammatory effects were determined using carrageenan-induced paw swelling method in SD rat. Paw swelling tests showed that pulsed phonophoresis group was more effective than control group and only gel application group. The conclusion of phonophoresis was found to improve significantly the skin permeation in vitro and the anti-inflammatory effect in vivo.

• Mass Spectrometry Letters
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• v.13 no.1
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• pp.20-25
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• 2022

Fargesin, a tetrahydrofurofuranoid lignan isolated from Flos Magnoliae, shows anti-inflammatory, anti-oxidative, anti-allergic, and anti-hypertensive activities. To evaluate the pharmacokinetics of fargesin in mice, a sensitive, simple, and selective liquid chromatography-high resolution mass spectrometric method using electrospray ionization and parallel reaction monitoring mode was developed and validated for the quantification of fargesin in mouse plasma. Protein precipitation of 6 µL mouse plasma with methanol was used as sample clean-up procedure. The standard curve was linear over the range of 0.2-500 ng/mL in mouse plasma with the lower limit of quantification level at 0.2 ng/mL. The intra- and inter-day coefficient variations and accuracies for fargesin at four quality control concentrations including were 3.6-11.3% and 90.0-106.6%, respectively. Intravenously injected fargesin disappeared rapidly from the plasma with high clearance values (53.2-55.5 mL/min/kg) at 1, 2, and 4 mg/kg doses. Absolute bioavailability of fargesin was 4.1-9.6% after oral administration of fargesin at doses of 1, 2, and 4 mg/kg to mice.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.262-267
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• 2010

Therapeutic duplication of prescriptions is the most frequently reported inappropriate drug use in Korea. To prevent significant problems during drug prescribing and dispensing, prospectively, development of standard including drug lists considered as therapeutic duplications for the prioritized drug classes first would be necessary. This study was aimed to analyze frequent drug classes of therapeutic duplications by healthcare providers in clinical practice settings. National health claims data for drug review and reimbursement (1,426,065 prescriptions dated March 19, 2008) were analyzed. Therapeutic duplication was defined as the prescription including more than 2 ingredients belonging to the same KFDA drug classification numbers that considered to have therapeutic similarities. The following 3 drug classes were mostly frequent therapeutic duplication classes: 114 anti-pyretics, analgesics and anti-inflammatory drugs; 117 drugs for psycho-nervous system; 141 Antihistamines. About 3.5% of overall prescriptions analyzed showed therapeutic duplications. This result might be starting step to develop DUR therapeutic duplication standard.

• Korean Journal of Medicinal Crop Science
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• v.17 no.6
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• pp.470-474
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• 2009

Achyrantes japonica (AJ) has been used to treat edema and arthritis in the traditional Korean medicine. To elucidate the anti-inflammatory and anti-nociceptive effects of ethanol extract of AJ, the carrageenan-induced paw edema using a plethysmometer and thermal hypersensitivity using the plantar test were measured. Ibuprofen was used as a control drug. Treatment with AJ (200mg/kg p.o.) significantly reduced paw edema, compared to the carrageenan - treated rats. In the plantar test, the thermal withdrawal latency in AJ - treated group was significantly increased than the carrageenan - treated group. The results indicate that AJ could have be the anti-inflammatory and anti-nociceptive properties.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.1
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• pp.55-82
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• 2008

Purpose: In this study, we evaluated anti-inflammatory activity and anti-thrombosis effect of Manbunbang(MBB) prescribed to chronic PID patients. Methods: We studied inhibitory effect of platelet aggregation, suppression effect of GPIIb/IIIa activity and inhibitory effect of $TXB_2$ and $PGE_2$ biosynthesis which were caused by ADP, epinephrine, collagen and arachidonic acid in vitro. And suppression of pulmonary embolism, changes of related factors in dextran coagulation condition model and anti-oxidative effect of oxidative damage were studied in vivo. Results: MBB extract showed LD50 of $200\;{\mu}g/ml$ or higher in mouse lung fibroblast cells, and significantly decreased the GPT and GPT level in dextran coagulation condition model compared to the control. MBB extract showed dose-dependent inhibition effect on platelet coagulation induced by ADP, epinephrine, collagen, arachidonic acid. MBB extract showed dose-dependent inhibition effect on GPIIb/IIIa activities compared to the control. MBB extract significantly suppressed TXB2 and PGE2 biosynthesis compared to the control. MBB extract suppressed pulmonary embolism triggered by collagen and epinephrine by 37.5% compared to the control. MBB extract significantly suppressed the decrease of speed of bloodstream caused by blood coagulation in dextran coagulation condition model compared to the control. Concluson : The results strongly suggest the anti-inflammatory activity of Manbunbang through anti-thrombus. Various applications using Manbunbang on inflammatory diseases are anticipated. Anti-oxidative efficacy comparison data between the Manbunbang prescription and the drug compositions may be used as important clinical information, and further investigation of anti-oxidative activities of Chrysanthemum indicum and Rhemaniae Radix should be followed.

• BMB Reports
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• v.46 no.12
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• pp.594-599
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• 2013

The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-${\alpha}$, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, $8.79{\times}10^5M^{-1}$. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.455-464
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• 2022

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.283-288
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• 2013

The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.