• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.597-605
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• 2018

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent $K^+$ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent $IC_{50}$ value of $5.04{\pm}1.05{\mu}M$ and a Hill coefficient of $0.78{\pm}0.06$. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of $Na^+$ channel inhibition.

• YAKHAK HOEJI
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• v.29 no.3
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• pp.130-143
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• 1985

Bumetanide, when given intravenously in dogs, induced a potent diuresis with an increased amounts of sodium and potassium excreted in urine due to inhibition of reabsorbing them in renal tubule. Furthermore, clearances of osmolar substance and para-aminohippuric acid were increased, but clearace of free water diminished without any change of creatinine clearance. Bumetanide, administered directly into a renal artery, elicited diuresis only in the infused(experimental) kidney by the same mode of action as in the intravenous cases in renal function of the dog. Renal effects of intravenous bumetanide after pretreatment with the small dose of indomethacin (5.0mg/kg) revealed reduction only in clearance of paraaminohippuric acid. However the much dose of indomethacin (5.0mg/kg+5.0mg/kg/hr) or arachidonic acid showed a significant inhibition in the change rates of all renal function by bumetanide. Morover, pretreatment of probenecid also made a marked reduction in renal effects induced by bumetanide. From the above results, it is thought that bumetanide causes diuretic action due to dual mechanism inhibiting reabsorption of electrolytes in loop of Henle and increasing blood flow in kindney, that are provoked through the mediation of prostaglandins.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.151-156
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• 2003

Cornis fructus have various biological effects and major chemical components have been tannins, saponins, ursolic acids, gallic acids, linoleic acids, morronisides, cornins and loganins. The main aim of the present study is measurment the effect of chloroform extract from Cornis fructus on proliferation inhibition and Cell death. Cells were cultured in the presence of chloroform extracts from Cornis fructus for 48 h. after 48h treatment of B16/F10 melanoma cells with chloroform extracts, the cells were observed a dose-dependent inhibitions of cell viability with cell death in their proliferation. the cells were estimated cell viability, cell number, total DNA fragmentation and chromatin condensation in a dose-dependent manner. It also caused cell death as measured by cell morphology, DNA fragmentation and nucleus chromatin condensation. therefore, these results suggest that chloroform extracts from C. fructus is inhibitory proliferation and is related to cell death in this cells.

• YAKHAK HOEJI
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• v.41 no.2
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• pp.255-259
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• 1997

Effects of the aqueous extract of Aquilariae Lignum (Thymelaeaceae) on the allergic reactions were investigated. Oral administration of this extract (50, 250, and 500mg/kg) exhi bited a dose-dependent inhibition on passive cutaneous anaphylactic reactions in rats. Administrations of this extract (500mg/kg, i.p.) at 60 min before and 5, 10 min after the compound 48/80 treatment (8mg/kg, i.p.) decreased the mortality rates to 0, 0, and 14.2%, respectively. The aqueous extract of Aquilariae Lignum (0.05 ~ 1.6mg/ml) showed a dose-related inhibition on histamine release from rat peritoneal mast cells. The morphological examination also clearly showed that the aqueous extract of Aquilariae Lignum prevented the degranulation of mast cells in rats.

• Natural Product Sciences
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• v.19 no.3
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• pp.206-214
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• 2013

The crocetin derivatives, crocin (1), gentiobiosyl glucosyl crocetin (3), and mono-gentiobiosyl crocetin (4) were isolated from the fruit of Gardenia jasminoides (Gj) and crocetin (2) from the processed fruit of Gj (PGj) by column chromatography. Their structures were determined on the basis of spectroscopic methods including IR, MS, and NMR (1D and 2D). These compounds were evaluated for their inhibition activity on melanin production in ${\alpha}$-MSH (melanocyte stimulating hormone) activated B16F10 cells. Compounds 1 - 4 reduced melanin content in a dose-dependent manner at concentrations of 20 - 60 uM. They also suppressed tyrosinase protein and m-RNA expressions dose dependently, assayed by western blot analysis, and RT-PCR experiment in B16F10 murine melanoma cells.

• Food Science and Biotechnology
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• v.18 no.6
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• pp.1532-1536
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• 2009

The objective of this study was to evaluate the antioxidant effects and acetylcholinesterase (AChE) inhibition activity of mulberry fruit extracts prepared by hot water (MFH) and 80% ethanol (MFE). Total polyphenolic contents of MFH and MFE were $195{\pm}3.4\;mg$ gallic acid equivalents/g MFH and $185{\pm}2.8\;mg$ gallic acid equivalents/g MFE. MFH and MFE significantly quenched 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide dose-dependently, and showed high chelating ability and reducing power in non-cellular systems. MFH and MFE also inhibited the formation of intracellular reactive oxygen species and lipid peroxidation, and elevated intracellular glutathione (GSH) levels in RAW264.7 cells. In addition, MFH and MFE also dose-dependently suppressed AChE activity.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.601-609
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• 1998

The present study was undertaken to examine the role of phospholipase $A_2\;(PLA_2)$ in oxidant-induced inhibition of phosphate transport in primary cultured rabbit renal proximal tubule cells. Uptakes of phosphate and glucose were dose-dependently inhibited by an oxidant t-butylhydroperoxide (tBHP), and the significant inhibition appeared at 0.025 mM of tBHP, whereas tBHP-induced alterations in lipid peroxidation and cell viability were seen at 0.5 mM. tBHP stimulated arachidonic acid (AA) release in a dose-dependent fashion. A $PLA_2$ inhibitor mepacrine prevented tBHP-induced AA release, but it did not alter the inhibition of phosphate uptake and the decrease in cell viability induced by tBHP. tBHP-induced inhibition of phosphate transport was not affected by a PKC inhibitor, staurosporine. tBHP at 0.1 mM did not produce the inhibition of $Na^+-K^+-ATPase$ activity in microsomal fraction, although it significantly inhibited at 1.0 mM. These results suggest that tBHP can inhibit phosphate uptake through a mechanism independent of $PLA_2$ activation, irreversible cell injury, and lipid peroxidation in primary cultured rabbit renal proximal tubular cells.

• Archives of Pharmacal Research
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• v.11 no.1
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• pp.33-40
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• 1988

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treating t-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate and t-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate with p-toluenesulfonic acid in $CH_3$CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at both in vitro and ex vivo levels. It was found from in vitro measurements that (E)-p-NTCP at $6.0{\times}10^{-5}M$ elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast, (E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with $IC_{50}$ values, $2.5{\times}10^{-7}M\;and\;1.4{\times}10^{-6}M$, respectively. It was also noted from (E)-m-NTCP that m-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According to ex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by (E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas, (E)-m-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between (E)-m-NTCP and (E)-p-NTCP were sought in relation to differing electron withdrawing effects of m- and p-substituents which will influence electron density of the side chain amino functions and the partitions.

• Journal of Acupuncture Research
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• v.18 no.2
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• pp.150-160
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• 2001

Objectives ; This study was undertaken to determine whether Carthami-Flos aquacapuncture (CFA) exerts protective effect against oxidant-induced inhibition of $Na^+-K^+$-ATPase activity in cerebral synaptosomes. Methods and Results ; The enzyme activity was dependent on incubation time and enzyme protein concentrations. An oxidant t-butylhydroperoxide (tBHP) at 1 mM concentration caused a significant inhibition of $Na^+-K^+$-ATPase activity, which was prevented by addition of 0.01% CFA. tBHP inhibition and CFA protection were independent on incubation time or enzyme protein concentrations. The enzyme activity was increased by ATP in a dose dependent manner. Effects of tBHP and CFA were not affected by ATP cocentrations. tBHP (1 mM) produced a significant increase in lipid peroxidation in cerebral synaptosomes, which was prevented by 0.01% CFA. CFA decreased oxygen free radicals generated induced by the phorbol-ester in a dose-dependent manner in human neutrophil. Conclusions ; These results suggest that CFA exerts protective effect against tBHP-induced inhibition of $Na^+-K^+$-ATPase activity, which is due to by an antioxidant action resulting from a direct scavenging effect of oxygen free radicals in the cerebral synaptosomes.

• Archives of Pharmacal Research
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• v.28 no.7
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• pp.848-853
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• 2005

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.