A novel pharmacophore with epinastine (1) and NSAID moieties (2-5) was designed by molecular hybridization approach. The hybrid compounds 6-9 were synthesized by EDCI/HOBt or HATU-mediated coupling of 1 with salicylic acid (2), mefenamic acid (3), indomethacin (4) and naproxen (5), respectively, and were assessed for their inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages in vitro. The Hybrids were found to exhibit significant NO production inhibitory effects with half-maximal inhibitory concentration (IC50) values ranging in between 15.96 ± 1.32 and 36.68 ± 2.53 μM and were non-cytotoxic to macrophages. Comparing the inhibition concentration (IC50), cytotoxicity concentration (CC50) and in vitro efficacy index (iEI), 6 (IC50 = 17.97 ± 1.92 μM; iEI = 11.13) and 9 (IC50 = 15.96 ± 1.32 μM; iEI = 12.53) were better suited than other hybrids as well as their parent compound. Our findings signify that hybrids 6 and 9 may serve as platforms for continued investigations for the development of more efficient anti-inflammatory agents.
This study was carried out to analyze the differences in p-hydroxylbenzyl alcohol (HBA) content, antitumor and anti-obesity activities and tyrosinase inhibitory activity between non-fermented G. elata (NFGP) and fermented G. elata powder. The HBA content, which is an index-component of G. elata decreased from 1.58 mg/g before fermentation to 1.07, 0.32, and 0.13 mg/g after the $1^{st}$ fermentation ($1^{st}$ FGP), $2^{nd}$ fermentation ($2^{nd}$ FGP) and $3^{rd}$ fermentation ($3^{rd}$ FGP), respectively. The anti-proliferation effects on the cell lines HT29 and AGS were significantly higher for the fermented G. elata than the NFGP. The antitumor activity was also increased in a fermentation number-dependent manner. During adipocyte differentiation, the ethanol extract of the $3^{rd}$ FGP inhibited lipid accumulation in 3T3-L1 cells significantly better than NFGP and the $1^{st}$ FGP, treated at the concentration of $10{\mu}g/mL$. The tyrosinase inhibitory activity of the $2^{nd}$ FGP at $600{\mu}g/mL$ over was higher than that of kojic acid. At the concentration of $1,000{\mu}g/mL$, the tyrosinase inhibitory activity was increased in a fermentation number-dependent manner. From these results, the fermented G. elata, especially the $3^{rd}$ FGP, is expected to be good candidate for the development of functional food and agents with antitumor, anti-obesity, and tyrosinase inhibitory potential.
Objectives: The object of this study was to observe the in vitro antibacterial effects of Wandae-tang extracts and combination of Wandae-tang extracts and Clindamycin against Gardnerella vaginalis ATCC14018. Methods: Antibacterial activities against Gardnerella vaginalis ATCC14018 of Wandae-tang extracts were detected using standard agar microdilution methods. In addition, the effects on the bacterial growth curve were also monitored at minimal inhibitory concentration(MIC) and $MIC{\times}2$ levels. The combination effects of Wandae-tang extracts with Clindamycin were observed by Checkerboard microtiter assay, and the effects of bacterial growth curve was treated with Wandae-tang extracts MIC+Clindamycin MIC, 1/2 MIC and 1/4 MIC, respectively. Results: MIC of Wandae-tang extracts and Clindamycin against Gardnerella vaginalis ATCC14018 were detected as $1.719{\pm}0.856$(0.782~3.125) $mg/m{\ell}$ and $0.010{\pm}0.006$ (0.004~0.016) ${\mu}g/m{\ell}$. In addition, Clindamycin and Wandae-tang extracts were also showed marked dosage-dependent inhibition of bacterial growth, and more dramatical inhibitions were detected in Clindamycin+Wandae-tang extracts MIC treatment. Fractional inhibitory concentration index in combination of Wandae-tang extracts and Clindamycin were detected as $0.294{\pm}0.052$(0.250~0.375) at Checkerboard microtiter assay. Conclusions: The results obtained in this study suggest that Wandae-tang extracts showed antibacterial effects against Gardnerella vaginalis ATCC14018, and they also showed dosage-dependent inhibitory effects on the bacterial growth. In addition, combination treatment of Wandae-tang extracts with Clindamycin showed more synergistically potent inhibitory effects on the growth of Gardnerella vaginalis.
Oh, Jong Min;Lee, Chaeyoung;Nam, Sang-Jip;Kim, Hoon
Journal of Microbiology and Biotechnology
/
v.31
no.7
/
pp.1022-1027
/
2021
Three compounds were isolated from marine-derived Streptomyces sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 1 (5,7-dihydroxy-2-isopropyl-4H-chromen-4-one) was a potent and selective inhibitor of MAO-A, with a 50% inhibitory concentration (IC50) of 2.70 µM and a selectivity index (SI) of 10.0 versus MAO-B. Compound 2 [5,7-dihydroxy-2-(1-methylpropyl)-4H-chromen-4-one] was a potent and low-selective inhibitor of MAO-B, with an IC50 of 3.42 µM and an SI value of 2.02 versus MAO-A. Compound 3 (1-methoxyphenazine) did not inhibit MAO-A or MAO-B. All three compounds showed little inhibitory activity against AChE, BChE, and BACE-1. The Ki value of compound 1 for MAO-A was 0.94 ± 0.28 µM, and the Ki values of compound 2 for MAO-A and MAO-B were 3.57 ± 0.60 and 1.89 ± 0.014 µM, respectively, with competitive inhibition. The 1-methylpropyl group in compound 2 increased the MAO-B inhibitory activity compared with the isopropyl group in compound 1. Inhibition of MAO-A and MAO-B by compounds 1 and 2 was recovered by dialysis experiments. These results suggest that compounds 1 and 2 are reversible, competitive inhibitors of MAOs and can be considered potential therapies for neurological disorders such as depression and Alzheimer's disease.
Im, Kyung Hoan;Choi, Jaehyuk;Baek, Seung-A;Lee, Tae Soo
Mycobiology
/
v.46
no.2
/
pp.159-167
/
2018
This study evaluated the in vitro and in vivo hypolipidemic effects of the medicinal mushroom Phellinus pini. The methanol extract (ME) of the fruiting body of Ph. pini was active against pancreatic lipase and cholesterol esterase with 99.14% and 67.23% inhibited activity at 1.0 mg/mL, respectively. It also inhibited 81.81% and 55.33% of ${\alpha}$-glucosidase and ${\alpha}$-amylase activities, respectively, at 2.0 mg/mL. Hyperlipidemia as induced by feeding rats with a high fat and cholesterol diet (HFC). HFC supplemented with a 5% fruiting body powder of Ph. pini (HFC + PhP) significantly reduced plasma total cholesterol, low-density lipoprotein cholesterol, and triglycerides in rats compared with HFC. The reduced levels were comparable to rats fed the normal control diet (NC). The atherogenic index of HFC + PhP rats was significantly lower than that of the HFC rats. The excretion of fecal total lipid and cholesterol in the HFC + PhP rats was significantly higher than those in the NC and HFC rats. Histopathological examinations demonstrated scant deposition of lipids in the liver of rats fed HFC + PhP. The dietary supplementation with the fruiting body powder provided natural plasma lipid and glucose lowering effects in experimental rats without adverse effects on the plasma biochemical parameters and liver function related enzyme activities. Therefore, the hypolipidemic effects of Ph. pini may be due to the inhibitory effects on pancreatic lipase, cholesterol esterase, ${\alpha}$-glucosidase, and ${\alpha}$-amylase, and excretion of excess lipids and cholesterol in the feces.
Park, Hae-Ji;Kang, Min-Jung;Lee, Jong-Hwan;Kim, Kwang-Hyeon
Korean Journal of Microbiology
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v.47
no.2
/
pp.163-166
/
2011
For reduction of side effects by anti-fungal agents, a less toxic anti-fungal substance or a synergistic substance with a new mechanism is needed. The anti-yeast substance (AYS) originated from Rahnella aquatilis strain AY2000 is like to be a heterogeneous protein. The AYS inhibited the growth of Candida albicans in culture broth, and AYS-treated cells were arrested in each phase during cell cycle. Among AYS-treated cells, the population of the cells belonging to sub-G1 phase was not increased during cell cycle. Therefore, AYS has rather yeaststatic than yeastcidal effect to C. albicans. Moreover, with combination of itraconazole or fluconazole, AYS had a synergistic anti-yeast activity against Saccharomyces cerevisiae based on the analysis of fractional inhibitory concentration index.
Kim, Yeji;Kim, Ohn Soon;Seo, Chang-Seob;Shin, Hyeun-Kyoo
Korean Journal of Pharmacognosy
/
v.44
no.1
/
pp.22-29
/
2013
This study was to investigate the quality of commercial Hwangryunhaedok-tang (Hwanglianjiedu-tang, HHT) extractive granules by comparing with HHT decoction. The contents of index components and the anti-inflammatory and antioxidative abilities of two different commercial HHT granules (HHT-2 and HHT-3) were compared with those of the HHT decoction (HHT-1). The contents were analyzed with HPLC. The anti-inflammatory effects were determined by measuring NO, $PGE_2$ and IL-6 in RAW 264.7 cell. We compared the anti-oxidative effects through ABTS radical scavenging activities. The range of contents of 7 ingredients was 0.42-36.54 mg/g in HHT-1, not detected-12.30 mg/g in HHT-2, not detected-18.79 mg/g in HHT-3. Although HHT-1, HHT-2, HHT-3 had the inhibitory effects on the production of NO, $PGE_2$ and the scavenging activities on ABTS, HHT-1 showed stronger effects than HHT-2, HHT-3 (HHT-1 > HHT-3 > HHT-2). HHT-1 inhibited the production of IL-6, while HHT-2, HHT-3 showed no inhibitory effects. It is necessary to find appropriate methods for extracting HHT and to establish standardized processes, in order to improve the quality of commercial traditional herbal formula.
Kim, Deok-Won;Park, Ji-Su;Oh, Eun-Ji;Yoo, Jin;Kim, Deok-Hyeon;Chung, Keun-Yook
Journal of Environmental Science International
/
v.30
no.11
/
pp.945-956
/
2021
In this study, the effects of single and binary heavy metals toxicity on the growth and phosphorus removal ability of Bacillus sp.. known as be a phosphorus-removing microorganism, were quantitatively evaluated. Cd, Cu, Zn, Pb, Ni were used as heavy metals. As a result of analysis of variance of the half of inhibition concentration and half of effective concentration for each single heavy metal treatment group, the inhibitory effect on the growth of Bacillus sp. was Ni < Pb < Zn < Cu < Cd. And the inhibitory effect on phosphorus removal by Bacillus sp. was Ni < Pb < Zn < Cu < Cd. When analyzing the correlation between growth inhibition and phosphorus removal efficiency of a single heavy metal treatment group, a negative correlation was found (R2 = 0.815), and a positive correlation was found when the correlation between IC50 and EC50 was analyzed (R2 = 0.959). In all binary heavy metal treatment groups, the interaction was an antagonistic effect when evaluated using the additive toxicity index method. This paper is considered to be basic data on the toxic effects of heavy metals when phosphorus is removed using phosphorus removal microorganisms in wastewater.
Objectives In this study, we investigated the clinical effect of Imoyongsutang and Imoyongsutang plus Maduryong on the viscosity of mucin solution, the instantly type allergy, the delayed type allergy, the carbon clearance, the pulmonary thromboembolism for the lung damaged rats and mice. Methods The gastric mucin and incubation time, pulmonary thromboembolism induced by sodium arachidonic acid, the pulmonary thromboembolism induced by ADP, vascular permeability response, non inhibitory effects, the delayed type hypersensitivity response to picryl chloride, serum $Na^+$ level, $K^+$ and $Cl^-$ level, ${\alpha}-index$ in phagocytic activity were measured. Results 1. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong gave some high significance results on the gastric mucin and incubation time on the viscosity of mucin solution in rats, and both groups had similar result. 2. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed feeble effect on the pulmonary thromboembolism induced by sodium arachidonic acid in mice, and both groups had similar result. 3. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed feeble effect on the pulmonary thromboembolism induced by ADP in mice, and after medication, the value was increased than the before one. 4. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were recognized. significance on vascular permeability response induced by histamine in rats. And the significance of the Imoyongsutang plus Maduryong is rather higher than that of Imoyongsutang. 5. The extract of Imoyongsutang recognized no significance symptoms on vascular permeability response induced by serotonin in rats, but the solid extract of Imoyongsutang plus Maduryong resulted recognized significance. 6. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed non inhibitory effects on the 48 hour homologous PCA in rats provoked by the IgE-like antibody against the egg albumin. 7. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were remarkably revealed inhibitory effect on the delayed type hypersensitivity response to picryl chloride in mice. And the significance of the latter is rather higher than that of the former. 8. The solid extract of Imoyongsutang was revealed inhibitory eects on the delayed type hypersensitivity response to SRBC in mice, but thffe solid extract of Imoyongsutang plus Maduryong recognized significance. 9. The solid extract of Imoyongsutang was recognized significance on the lung TBA value of $O_3$ intoxicated rats, but the solid extract of Imoyongsutang plus Maduryong recognized no significance. 10. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong was recognized significance on serum $Na^+$ level in $O_{3}-intoxicated$ rats. And the significance of the latter is rather higher than that of the former. 11. Both the solid extracts of Imoyongsutang and Imoyongsutang plus Maduryong were revealed non inhibitory effects on serum $K^+$ and $CL^-$ level $O_{3}-intoxicated$ Rats 12. The solid extracts Imoyongsutang was recognized significance on K-index in phagocytic activity in mice, but the solid extract of Imoymgsutang plus Maduryong recognized no significance. 13. The solid extract Imoyongsutang was recognized on significance on ${\alpha}-index$ in phagocytic activity in mice. but the solid extract of Imoyongsutang plus Maduryong recognized significance. Conclusions According to the above findings, it is suggested that the sold extract of Imoyongsutang and Imoyongsutang plus Maduryong were revealed effects on asthma cough or dyspnea caused by the abnormal rising of lung-allergy and throat discomfort so that they retain effectiveness on the instantly and delayed type allergy, the pulmonary thromboembolism and the lung damages in rats and mice.
This work was designed as basic studies on the development of diet for the treatment of obesity. The effect of alginic acid which is the major component of brown algae was investigated by comparing with agar, cellulose, carboxymethylcellulose (CMC), chitin, and lignin as dietary fibers. These dietary fibers ($10\%$) supplemented to basic diet were fed ad libitum to Sprague Dawley rat for 4 weeks, and the inhibitory effects on obesity were evaluated by measuring body weight gain and feed efficiency, the content of glucose and cholesterol in serum, lipase activity in serum, lipid content in liver, adipose tissue around epididymis and ovarium, and Lee index etc. Among the inhibitory effect of these dietary fibers on obesity, lignin was the most effective (p<0.001), followed by Na-alginate (p<0.01) for body weight gain, but lignin was the most effective, followed by CMC, and followed by Na-alginate for feed efficiency (p<0.001). In the inhibitory effects on lipid accumulation in liver and adipose tissue around epididymis and ovarium, lignin and Na-alginate group among these dietary fibers were more effective than others, but there was no significant difference between male and female. The inhibitory effect on obesity evaluated by Lee index was effective in the order of Na-alginate>lignin>CMC>chitin>cellulose (p<0.001). The decreasing effects of lipid content in liver by dietary fibers were found in the order of agar>CMC>cellulose>Na-alginate>chitin>lignin (p<0.001). Glucose content in serum was significantly decreased in cases of CMC, lignin and Na-alginate, whereas a slight difference was found in chitin, but cholesterol content in serum was decreased for all dietary fibers examined except cellulose group. The increasing effect of lipase activity in plasma was found in cases of Na-alginate and chitin, while cellulose, CMC and lignin groups were decreased.
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