Tacrine-induced Cytotoxicity Research Articles

모링가 잎 추출물의 항당뇨, 알코올 대사 및 간 보호 활성

본 연구에서는 비타민과 단백질이 풍부하여 높은 영양가를 가지고 있으며, 콜레스테롤 제거 및 간 손상 방지와 염증, 심장병 등의 치료 효과가 있는 것으로 알려진 모링가 잎 추출물의 새로운 소재로서의 가능성을 검토하고자 항산화 활성과 항당뇨, 항염증 및 알코올분해능을 탐색하였다. 모링가열수 및 에탄올 추출물의 총페놀 함량은 각각 45.49와 63.06 mg TAE/g으로 나타났다. 1,1-Diphenyl-2-picrylhydrazyl radical 소거능은 1 mg/mL 농도의 열수 및 에탄올 추출물에서 각각 60.81%와 71.29%로 에탄올 추출물의 소거능이 높게 나타났다. 모링가 열수 및 에탄올 추출물의 superoxide dismutase 유사 활성은 농도 의존적으로 증가하였으며, 5 mg/mL 농도의 열수 및 에탄올 추출물에서 각각 2.82%와 7.40%로 에탄올 추출물의 활성이 높은 것으로 나타났다. 모링가 추출물의 혈당 강하 효과를 확인하기 위해 실시한 α-glucosidase 활성 억제 효과는 5 mg/mL 농도의 열수 및 에탄올 추출물에서 45.19%와 88.14%로 에탄올 추출물의 저해 활성이 유의적으로 높게 나타났다. 숙취 해소능을 알아보기 위해 alcohol dehydrogenase 및 acetaldehyde dehydrogenase 활성을 측정한 결과 두 효소 모두 모링가 열수 및 에탄올 추출물의 농도에 의존적으로 증가하였다. Lipopolysaccharide(LPS)에 의하여 유도된 NO 합성은 열수 및 에탄올 추출물 1 mg/mL 농도에서 28.50%와 7.90%로 LPS 처리군(41.96%)보다 각각 32.1%와 81.2% 현저히 감소하였으며, 모링가 열수 및 에탄올 추출물이 tacrine으로 유도된 Hep3B 간암 세포주에 대하여 유의적인 보호 활성을 나타냈다. 이상의 결과에서와 같이 모링가 잎 열수 및 에탄올 추출물은 우수한 항당뇨, 항염증, 숙취 해소 효과 및 간세포 보호 효과가 있는 것으로 나타났기에 기능성 소재로서의 활용도가 높을 것으로 판단된다.

산겨릅나무 줄기 추출물의 항당뇨, 알코올 대사 효소 및 간 보호 활성

This study was carried out to investigate the antidiabetic, alcohol metabolism, anti-inflammatory, and hepatoprotective effects of Acer tegmentosum extracts (ATE). A. tegmentosum has been traditionally used as a folk medicine to treat hepatic disorders. The antioxidative activities of ATE were measured by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and superoxide (SOD) assay. DPPH radical scavenging and SOD activities of ATE were about 89% and 82.9% at 0.5 μg/mL, respectively. Alcohol dehydrogenase and acetaldehyde dehydrogenase activities were 118.0% and 177% at 2 mg/mL, respectively. α-Glucosidase inhibitory activity of ATE was 75% higher at 50 μg/mL and remarkably increased in a dose-dependent manner. Nitric oxide productions in macrophage RAW 264.7 cells stimulated by lipopolysaccharide was reduced to 16.7% by addition of ATE at 1 mg/mL. ATE showed significant protective effects against tacrine-induced cytotoxicity in Hep G2 cells at 100 μg/mL. Based on our results, we conclude that ATE may be used as a major pharmacological agent and anti-diabetic, anti-hepatitis, and anti-inflammatory remedy.

A new phenyl glycoside from the aerial parts of Equisetum hyemale

A new phenyl glycoside, 2-(sophorosyl)-1-(4-hydroxyphenyl)ethanone (9), was isolated from the ethanolic extract of the aerial parts of Equisetum hyemale L., together with eight known compounds (1–8). The structures of these compounds were elucidated using a combination of spectroscopic analyses and chemical method. Of these nine compounds, 4 and 7 showed hepatoprotective effects towards tacrine-induced cytotoxicity in Hep 3B cells with EC50 values of 42.7 ± 1.5 and 132.6 ± 2.8 μM, respectively.

Effects of White Radish (Raphanus sativus) Enzyme Extract on Hepatotoxicity.

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The IC50 values of REE in human liver derived HepG2 cells was over 5,000 μg/ml in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrineinduced cytotoxicity and the EC50 value was 1,250 μg/ml. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activitiy at 100 μg/ml. Moreover, we tested the effect of REE on carbon tetrachloride (CCl4)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to CCl4-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by CCl4. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or CCl4.

상황버섯(Phellinus pini)의 라디칼 소거작용

Phellinus pini (CY001) 추출물에서의 페놀류성분의 농도는 P. pini (CY001)분획 g 당 GAEs mg으로 나타내었고, P. pini의 EtOAc 분획 (436.5 mg GAEs/g)이 다른 분획에 비해 가장 높은 함량을 나타내었다. 환원력과 같은 항산화 활성을 screening 하기 위해 몇 가지 생화학적 시험이 수행되었고, 그것은 2, 2-diphenyl-1-picrylhydrazyl(DPPH) 라디칼 소거작용, NBT/XO superoxide system, DCF/AAPH peroxyl radicals 저해능 등이다. 여섯 개의 버섯추출물 분획 중에서 EtOAc 분획이 DPPH, superoxide 라디칼, peroxyl 라디칼 소거작용이 뛰어났고, <TEX>$IC_{50}$</TEX> values는 각각 <TEX>$11.49\;{\mu}g/ml$</TEX>, <TEX>$8.32\;{\mu}g/ml$</TEX>, and <TEX>$1.91\;{\mu}g/ml$</TEX>이었다. P. pini (CY001)의 EtOAc 분획은 중요한 효소적 지질과산화 저해와 cytotoxicity 없이 RAW 264.7 macrophages의 LPS 유도 NO 생성을 효과적으로 감소시켰다. 또한 EtOAc 분획이 HepG2 cell의 타크린 유도 cytotoxicity에서 간 보호 작용을 나타내었다. 이러한 결과를 바탕으로 P. pini (CY001)가 라디칼 소거작용을 하는 성분을 함유한 천연 항산화제로써의 잠재력을 갖고 있는 것으로 사료된다. The concentration of phenolics in Phellinus pini (CY001) extracts, expressed as mg of GAEs per g of P. pini fractions, and the EtOAc fraction (436.5 mg GAEs/g) of P. pini had a higher phenolic content than other fractions. Several biochemical assays were used to screen antioxidant properties such as reducing power, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, NBT/XO superoxide system and inhibition of DCF/AAPH peroxyl radicals. Among the six mushroom extracts, the EtOAc fraction from P. pini (CY001) showed the most potent DPPH radical, superoxide radical, and peroxyl radical scavenging activities, with <TEX>$IC_{50}$</TEX> values of <TEX>$11.49\;{\mu}g/ml$</TEX>, <TEX>$8.32\;{\mu}g/ml$</TEX>, and <TEX>$1.91\;{\mu}g/ml$</TEX>, respectively. The EtOAc fraction of P. pini (CY001) significantly inhibited enzymatic lipid peroxidation and effectively attenuated LPS-induced NO production of RAW 264.7 cells without cytotoxicity. We also found that the EtOAc fraction had a significant hepato-protectant effect on tacrine-induced cytotoxicity in HepG2 cells. These findings suggest that P. pini (CY001) may have potential as a natural antioxidant, which contains compound(s) with radical scavenging activity.

Tribuli fructus constituents protect against tacrine-induced cytotoxicity in HepG2 cells

A new phenolic amide, tribulusimide D (4-hydroxy-N-[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propen-1-yl]-3-methoxybenzamide) (1), together with a known phenolic amide, terrestriamide ((E)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-oxoethyl]-prop-2-enamide) (2) and a flavonol glycoside, quercetin-3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (3) were isolated from the H2O extract of Tribuli Fructus. Compounds 1 and 3 showed significant hepatoprotective activities, with EC50 values of 13.46 +/- 0.2 and 7.06 +/- 0.7 microM, respectively, against tacrine-induced cytotoxicity in HepG2 cells.

Chromone glycosides and hepatoprotective constituents of Hypericum erectum

Two chromone glycosides, hyperimone A [7-(beta-D-glucopyranosyloxy)-5-hydroxy-2-(1-methylethyl)-4H-1-benzopyran-4-one (1)] and hyperimone B [7-(beta-D-glucopyranosyloxy)-5-hydroxy-3-methyl-4H-1-benzopyran-4-one (2)], together with six known compounds were isolated from the methanolic extract of the whole plant of Hypericum erectum. 1,3,5,6-Tetrahydroxyxanthone (5) and I3, II8-biapigenin (6) showed moderate hepatoprotective activity with EC(50) values of 160.2 +/- 0.6 microM and 217.7 +/- 1.3 microM, respectively, against tacrine-induced cytotoxicity in HepG2 cells.

In Vitro hepatoprotective compounds from Suaeda glauca

Bioassay-guided fractionation of the MeOH extract of Suaeda glauca yielded four phenolic compounds, methyl 3,5-di-O-caffeoyl quinate (1) and 3,5-di-O-caffeoyl quinic acid (2), isorhamnetin 3-O-beta-D-galactoside (3), and quercetin 3-O-beta-D-galactoside (4). Compounds 1 and 2 were hepatoprotective against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells with the EC(50) values of 72.7+/-6.2 and 117.2+/-10.5 microM, respectively. Silybin as a positive control showed an EC(50) value of 82.4+/-4.1 microM.

Cytoprotective constituent of hoveniae lignum on both hep G2 cells and rat primary hepatocytes

A phytochemical investigation of the EtOH extract of Hoveniae Lignum yielded four phenolic compounds, phloretin (1), 5-(4'-hydroxyphenyl)-gamma-valerolactone (2), (-)-epiafzelechin (3), and maesopsin (4). Compound 1 was hepatoprotective against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells with an EC50 value of 37.55 +/- 0.42 microM. Compound 1 (0.4-200 microM) also significantly reduced tert-butyl hydroperoxide-induced cytotoxicity in rat primary hepatocytes as measured by the cellular leakage of lactate dehydrogenase and the level of aspartate transaminase.

Hepatoprotective Compounds of the Roots of Cudrania tricuspidata on Tacrine-Induced Cytotoxicity in Hep G2 Cells

The bioassay-guided fractionation of the MeOH extract of the root barks of Cudrania tricuspidata furnished three hepatoprotective compounds, gerontoxanthone A (2), cudraflavone B (4), gericudranin E (5), together with four prenylated xanthones, cudraxanthone B (3), isocudraxanthone K (6), cudraxanthone C (7), cudraxanthone H (8), and a prenylated flavanone, euchrestaflavanone C (1). Compounds 4 and 5 showed significant hepatoprotective effects with the EC50 values of 37.39+/-0.4 and 39.87+/-0.7 microM, respectively, and compound 2 showed moderate hepatoprotective effect with an EC50 value of 125.9+/-1.5 microM, against tacrine-induced cytotoxicity in Hep G2 cells. Silybin as positive control showed an EC50 value of 84.76+/-0.5 microM. Isocudraxanthone K (6) is a new compound.

Hepatoprotective constituents of the edible brown alga Ecklonia stolonifera on tacrine-induced cytotoxicity in Hep G2 cells.

In this study, ethanolic extracts from 18 seaweed variants were assessed for hepatoprotective activity against tacrine-induced cytotoxicity in Hep G2 cells. Only one of these, Ecklonia stolonifera Okamura (Laminariaceae), a member of the brown algae, exhibited promising hepatoprotective activity. Bioassay-guided fractionation of the active ethyl acetate (EtOAc) soluble fraction obtained from the ethanolic extract of E. stolonifera, resulted in the isolation of several phlorotannins [phloroglucinol (1), eckstolonol (2), eckol (3), phlorofucofuroeckol A (4), and dieckol (5)]. Compounds 2 and 4 were determined to protect Hep G2 cells against the cytotoxic effects of tacrine, with EC50 values of 62.0 and 79.2 microg/mL, respectively. Silybin, a well characterized hepatoprotective agent, was used as a positive control, and exhibited an EC50 value of 50.0 microg/mL. It has been suggested that the phlorotannins derived from marine brown algae might prove useful sources in the development of novel hepatoprotective agents.

Hepatoprotective constituents ofcudrania tricuspidata

Phytochemical investigation of the MeOH extract of the root barks of Cudrania tricuspidata Bureau (Moraceae), as guided by hepatoprotective activity in vitro, furnished four isoprenylated xanthones, cudratricusxanthone A (1), cudraxanthone L (2), cudratricusxanthone E (3), and macluraxanthone B (4). All of these compounds showed the significant hepatoprotective effect on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. Compounds 1, 2, and 4 also exhibited the significant hepatoprotective effect on nitrofurantoin-induced cytotoxicity in human liver-derived Hep G2 cells.

Phenolic Constituents of Galla Rhois with Hepatoprotective Effects on Tacrine- and Nitrofurantoin-Induced Cytotoxicity in Hep G2 Cells

The bioassay-guided fractionation of the MeOH extract of Galla Rhois furnished two hepatoprotective compounds, an equilibrium mixture of 3-galloyl-gallic acid and 4-galloyl-gallic acid isomers (3), 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (4), and two inactive phenolic compounds, gallic acid methyl ester (1) and gallic acid (2). Compounds 3 and 4 showed significant hepatoprotective effects with EC50 values of 70.39+/-5.4 and 29.51+/-0.7 microM, respectively, against tacrine-induced cytotoxicity, and 150.9+/-6.4 and 23.81+/-0.5 microM, respectively, against nitrofurantoin-induced cytotoxicity in Hep G2 cells.

Hepatoprotective and free radical scavenging activities of phenolic petrosins and flavonoids isolated from Equisetum arvense

Hepatoprotective activity-guided fractionation of the MeOH extract of Equisetum arvense L. (Equisetaceae) resulted in the isolation of two phenolic petrosins, onitin ( 1) and onitin-9- O-glucoside ( 2), along with four flavonoids, apigenin ( 3), luteolin ( 4), kaempferol-3- O-glucoside ( 5), and quercetin-3- O-glucoside ( 6). Among these, compounds 1 and 4 exhibited hepatoprotective activities on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells, displaying EC 50 values of 85.8 ± 9.3 μM and 20.2 ± 1.4 μM, respectively. Silybin, used as a positive control, showed the EC 50 value of 69.0 ± 3.3 μM. Compounds 1 and 4 also showed superoxide scavenging effects (IC 50 = 35.3 ± 0.2 μM and 5.9 ± 0.3 μM, respectively) and DPPH free radical scavenging effect (IC 50 of 35.8 ± 0.4 μM and 22.7 ± 2.8 μM, respectively). These results support the use of this plant for the treatment of hepatitis in oriental traditional medicine.

Hepatoprotective phenolic constituents of Rhodiola sachalinensis on tacrine-induced cytotoxicity in Hep G2 cells.

Two hepatoprotective phenolic compounds, kaempferol (2) and salidroside (4), were isolated from the roots of Rhodiola sachalinensis together with two inactive compounds cinnamyl alcohol (1) and daucosterol (3) based on the hepatoprotective activity against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC(50) values of compounds 2 and 4 were 33.5 and 51.3 micro m, respectively. Silybin as a positive control showed an EC(50) value of 68.4 micro m.

Hepatoprotective and free radical scavenging activities of prenylflavonoids, coumarin, and stilbene from Morus alba.

Chemical investigation of the EtOH extract of Morus alba L. (Moraceae), as guided by free radical scavenging activity, furnished 5,7-dihydroxycoumarin 7-methyl ether (1), two prenylflavones, cudraflavone B (2) and cudraflavone C (3), and oxyresveratrol (4). Compounds 1 and 4 showed superoxide scavenging effects with the IC(50) values of 19.1 +/- 3.6 and 3.81 +/- 0.5 microM, respectively. Compound 4 exhibited a DPPH free radical scavenging effect (IC(50) = 23.4 +/- 1.5 microM). Compounds 2 and 4 showed hepatoprotective effects with EC(50) values of 10.3 +/- 0.42 and 32.3 +/- 2.62 micro, respectively, on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells.

Sesquiterpenes with hepatoprotective activity from Cnidium monnieri on tacrine-induced cytotoxicity in Hep G2 cells.

Bioassay-guided fractionation of the EtOH extract of Cnidium monnieri (Apiaceae) furnished two hepatoprotective sesquiterpenes, torilin (1) and torilolone (2), together with a new derivative, 1-hydroxytorilin (3). Compounds 1 and 2 showed hepatoprotective effects on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC50 values of compounds 1 and 2 were 20.6 +/- 1.86 (P < 0.01) and 3.6 +/- 0.1 (P < 0.01) microM, respectively. Silybin as a positive control showed an EC50 value of 69.0 +/- 3.4 microM.

Bakuchiol: a hepatoprotective compound of Psoralea corylifolia on tacrine-induced cytotoxicity in Hep G2 cells.

Bioassay-guided fractionation of the H(2)O extract of the seeds of Psoralea corylifolia furnished one hepatoprotective compound, bakuchiol (1), together with two moderately active compounds, bakuchicin (2) and psoralen (3), on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells. The EC(50) values of compounds 1 - 3 are 1.0, 47.0, 50.0 microg/ml, respectively. Silymarin as a positive control showed the EC(50) value with 5.0 microg/ml.