Toxicity Effects of Chinese Herbal ‘Five-seeds’ Formulation on Human Kidney HEK-293 and Chang Liver Cells

‘Five-seeds’ formulation (Lycium barbarum, Cuscuta chinensis Lam, Rubus idaeus, Schisandra chinensis, Plantago asiatica) have been used by Chinese medicine practitioner for the treatment of male infertility for a long time. The present study aims to investigate the potential toxicity effects of the individual herb used in ‘five-seeds’ formulation and as a concoction on human HEK293 and Chang liver cells, using cell viability MTT assay and SubG1 flow cytometry analysis. Percentage of cell viability from samples (1, 25, 50, 75, 100 mg/mL) decreased as the concentration increased. Half maximal inhibitory concentration (IC50) values indicated that Cuscuta chinensis, Rubus idaeus and Schisandra chinensis are among the most toxic herb samples on HEK293 cells, with the IC50 values less than 22 mg/mL. On the other hand, Rubus idaeus (IC50 value 20.1 mg/mL) and Schisandra chinensis (IC50 value 17.8 mg/mL) were found to have the highest toxicity effect on Chang liver cells. Plantago asiatica and Lycium barbarum (IC50 more than 67 mg/mL) are the least toxic herbs tested on both human HEK293 kidney and Chang liver cells. ‘Five-seeds’ herbal formulation had IC50 values of 33 mg/mL and 38.5 mg/mL on HEK293 and Change liver cells respectively, suggesting that ‘five seeds’ formulation has modulated the toxicity effect of the mixed herbs used in this formula. Apoptotic cells in SubG1 phase were also found to be significantly low for HEK293 (13.08%) and Chang liver cells (10.17%) with the treatment of 25 mg/mL of ‘five seeds’ formulation. Toxicity effect of five-seeds’ herbal formulation has seemingly been modulated when all the five herbs mixed as a concoction, and potentially non-toxic as a concoction to HEK293 kidney and Chang liver cells. However, more investigations should be done to draw a solid conclusion.

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Micropillar/Microwell Chip Assessment for Detoxification of Bisphenol A with Korean Pear (Pyrus pyrifolia)

Micromachines ◽

10.3390/mi11100922 ◽

2020 ◽

Vol 11 (10) ◽

pp. 922

Author(s):

Dong Lee ◽

Moo-Yeal Lee ◽

Sukkil Koh ◽

Mihi Yang

Keyword(s):

Bisphenol A ◽

Liver Cells ◽

Pyrus Pyrifolia ◽

Endocrine Disrupting Chemical ◽

Protein Levels ◽

Ic50 Value ◽

Endocrine Disrupting ◽

Cultured Liver Cells ◽

Ic50 Values ◽

Hep3b Cells

A micropillar/microwell chip platform with 3D cultured liver cells has been used for HTP screening of hepatotoxicity of bisphenol A (BPA), an endocrine-disrupting chemical. We previously found the hepatotoxicity of BPA is alleviated by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase 2 (ALDH2). In this study, we have tested potential BPA detoxification with Korean pear (Pyrus pyrifolia) extract, stimulators of ADH and ALDH, as well as arbutin, a reference compound in the pears, on the micropillar/microwell chip platform with human liver cells. Surprisingly, the toxicity of BPA was reduced in the presence of Korean pear extract, indicated by significantly increased IC50 values. The IC50 value of BPA with Korean pear extract tested against HepG2 cells was shifted from 151 to 451 μM, whereas those tested against Hep3B cells was shifted from 110 to 204 μM. Among the tested various concentrations, 1.25, 2.5, and 5 mg/mL of the extract significantly reduced BPA toxicity (Ps < 0.05). However, there was no such detoxification effects with arbutin. This result was supported by changes in protein levels of ADH in the liver cells.

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Inhibition by Glaucocalyxin A of Aggregation of Rabbit Platelets Induced by ADP, Arachidonic Acid and Platelet-Activating Factor, and Inhibition of [3H]-PAF Binding

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648470 ◽

1992 ◽

Vol 67 (04) ◽

pp. 458-460 ◽

Cited By ~ 12

Author(s):

Zhang Bin ◽

Long Kun

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Platelet Activating Factor ◽

Northeastern China ◽

Ethereal Extract ◽

Ic50 Value ◽

Rabbit Platelets ◽

Ic50 Values ◽

Induced Aggregation

SummaryGlaucocalyxin A is a new diterpenoid isolated from the ethereal extract of the leaves of Rabdosia japonica (Burm f) Hara var glaucocalyx (Maxim) Hara (Labiatae) collected in the northeastern China. When it was incubated with washed rabbit platelets, glaucocalyxin A inhibited ADP- or arachidonic acid-induced platelet aggregation with IC50 values of 4.4 μmol/1, 14.1 μmol/1 respectively. Glaucocalyxin A also inhibited PAF-induced aggregation of rabbit platelets which were refractory to ADP and arachidonic acid with an IC50 value of 13.7 μmol/1. Analysis of [3H]-PAF binding showed that glaucocalyxin A prevented [3H]-PAF binding to intact washed rabbit platelets with an IC50 value of 8.16 μmol/1, which was consistent with its inhibition of PAF-induced platelet aggregation.

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Inhibition of Protein Tyrosine Phosphatase 1B by Lutein Derivatives isolated from Mexican Oregano (Lippia graveolens)

Phytothérapie ◽

10.3166/phyto-2018-0074 ◽

2018 ◽

Vol 17 (3) ◽

pp. 134-139

Author(s):

R.M. Perez-Gutierrez

Keyword(s):

Protein Tyrosine Phosphatase ◽

Inhibitory Activity ◽

Spectroscopic Data ◽

Methanol Extract ◽

Tyrosine Phosphatase ◽

Positive Control ◽

Protein Tyrosine Phosphatase 1B ◽

Protein Tyrosine ◽

Ic50 Value ◽

Ic50 Values

Methanol extract from Lippia graveolens (Mexican oregano) was studied in order to identify inhibitory bioactives for protein tyrosine phosphatase 1B (PTP1B). Known flavone as lutein (1), and another flavone glycoside such as lutein-7-o-glucoside (2), 6-hydroxy-lutein-7-ohexoside (3) and lutein-7-o-ramnoide (4) were isolated from methanol extract of aerial parts of the Lippia graveolens. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR, MS and compared with spectroscopic data previously reported. These flavones were evaluated for PTP1B inhibitory activity. Among them, compounds 1 and 3 displayed potential inhibitory activity against PTP1B with IC50 values of 7.01 ± 1.25 μg/ml and 18.4 μg/ml, respectively. In addition, compound 2 and 4 showed moderate inhibitory activity with an IC50 value of 23.8 ± 6.21 and 67.8 ± 5.80 μg/ml respectively. Among the four compounds, luteolin was found to be the most potent PTP1B inhibitor compared to the positive control ursolic acid, with an IC50 value of 8.12 ± 1.06 μg/ml. These results indicate that flavonoids constituents contained in Lippia graveolens can be considered as a natural source for the treatment of type 2 diabetes.

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Synthesis and Assessment of Novel Anti-chlamydial Benzylidene Acylhydrazides Derivatives

Letters in Drug Design & Discovery ◽

10.2174/1570180814666170526170227 ◽

2018 ◽

Vol 15 (1) ◽

pp. 31-36 ◽

Cited By ~ 5

Author(s):

Xiaofeng Bao ◽

Ying Xue ◽

Chao Xia ◽

Yin Lu ◽

Ningjing Yang ◽

...

Keyword(s):

Inhibitory Effect ◽

Dependent Manner ◽

Iron Starvation ◽

Hydrochloride Salt ◽

Obligate Intracellular ◽

Biphasic Life Cycle ◽

Ic50 Value ◽

Ic50 Values ◽

Dose Dependent ◽

Better Than

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

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Synthesis and Structure−Activity Relationship Studies of N-monosubstituted Aroylthioureas as Urease Inhibitors

Medicinal Chemistry ◽

10.2174/1573406416999200818152440 ◽

2020 ◽

Vol 16 ◽

Author(s):

Wei-Wei Ni ◽

Hai-Lian Fang ◽

Ya-Xi Ye ◽

Wei-Yi Li ◽

Li Liu ◽

...

Keyword(s):

Regression Analysis ◽

Mammalian Cells ◽

Intact Cell ◽

Linear Regression Analysis ◽

Positive Control ◽

Acetohydroxamic Acid ◽

Urease Inhibitors ◽

Ic50 Value ◽

Ic50 Values ◽

Low Cytotoxicity

Background: Thiourea is a classical urease inhibitor usually as a positive control, and many N,N`-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N`-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thioureas with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated viasurface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed IC50 value of 0.060 ±0.004μM against cell-free urease, which bound to urea binding site with a very low KDvalue (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11was also demonstrated having very low cytotoxicity to mammalian cells. Conclusion: These results revealed that N-monosubstituted aroylthioureas clearly bind the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by ure-ase-containing pathogens.

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Staurosporine Induces Telophase Arrest and Apoptosis Blocking Mitosis Exit in Human Chang Liver Cells

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1997.6985 ◽

1997 ◽

Vol 236 (3) ◽

pp. 594-598 ◽

Cited By ~ 13

Author(s):

Myint Swe ◽

K.H. Sit

Keyword(s):

Liver Cells ◽

Chang Liver

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Studies on Thymidine Kinase, Thymidylate Kinase, and Deoxycytidylate Deaminase of Chang Liver Cells

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)93537-4 ◽

1968 ◽

Vol 243 (8) ◽

pp. 1979-1984

Author(s):

P Eker

Keyword(s):

Thymidine Kinase ◽

Liver Cells ◽

Thymidylate Kinase ◽

Chang Liver

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Novel photochromic inhibitor for mitotic kinesin Eg5 which forms multiple isomerization states

The Journal of Biochemistry ◽

10.1093/jb/mvab035 ◽

2021 ◽

Author(s):

Islam Md Alrazi ◽

Kei Sadakane ◽

Shinsaku Maruta

Keyword(s):

Inhibitory Activity ◽

Molecular Motor ◽

The Novel ◽

Precise Control ◽

Atpase Assay ◽

Ic50 Value ◽

Motor Activities ◽

Ic50 Values ◽

Kinesin Eg5 ◽

Mitotic Kinesin Eg5

Abstract The mitotic kinesin Eg5 is a plus-end directed homotetrameric molecular motor essential for the formation of bipolar spindles during cell division. Kinesin Eg5 is overexpressed in cancer cells and hence considered as a target for cancer therapy; the inhibitors specific for Eg5 have been developed as anticancer drugs. In this study, we synthesized a novel functional photoresponsive inhibitor composed of spiropyran and azobenzene derivatives to control Eg5 function with multistage inhibitory activity accompanied by the formation of different isomerization states. The photochromic inhibitor spiropyran-sulfo-azobenzene (SPSAB) exhibited three isomerization states: spiro (SP)-trans, merocyanine (MC)-cis and MC-trans, upon exposure to visible light, ultraviolet and in the dark, respectively. SPSAB-induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with photoisomerization among the three states. Among the three isomerization states of SPSAB, the SP-trans isomer showed potent inhibitory activity at an IC50 value of 30 µM in the basal ATPase assay. MC-trans and MC-cis exhibited less inhibitory activity at IC50 values of 38 and 86 µM, respectively. The results demonstrated that the novel photochromic inhibitor enabled precise control of Eg5 function at three different levels using light irradiation.

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Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Acta Endocrinologica ◽

10.1530/eje.0.1410035 ◽

1999 ◽

pp. 35-39 ◽

Cited By ~ 21

Author(s):

M Gallo ◽

M Aragno ◽

V Gatto ◽

E Tamagno ◽

E Brignardello ◽

...

Keyword(s):

Lipid Peroxidation ◽

Protective Effect ◽

Human Liver ◽

Antioxidant Properties ◽

Liver Cells ◽

Threshold Concentration ◽

Blue Staining ◽

Lag Phase ◽

Human Liver Cell ◽

Chang Liver

OBJECTIVE: Dehydroepiandrosterone (DHEA) is a widely studied steroid hormone with multi-functional properties. Reports suggest that some of the many activities of DHEA are due to its protective effect against lipid peroxidation. Nevertheless, the antioxidant properties of DHEA are still the subject of debate. The aim was to evaluate whether its two opposed effects on lipid peroxidation reported in the literature may be dependent on schedule and doses used. METHODS: Chang liver cells, a line derived from normal human liver, were grown in media containing either no steroids (control) or DHEA at concentrations ranging from 0.1 micromol/l to 50 micromol/l. At specific times, cultures were halted and cells received a pro-oxidant stimulus (cumene (CuOOH) 0.5 mmol/l), at which time cell viability (by trypan blue staining and lactate dehydrogenase (LDH) release) and thiobarbituric acid reactive substances (TBARS) concentration (spectrophotometrical assay) were evaluated. RESULTS: At concentrations ranging from 0.1 micromol/l to 1 micromol/l, DHEA protects Chang liver cells against lipid peroxidation and/or death induced by cumene. This effect disappears if the concentration is increased to 10 micromol/l; at higher concentrations (50 micromol/l) a pro-oxidant/cytotoxic effect of DHEA appears. CONCLUSIONS: DHEA exhibits two opposed effects on lipid peroxidation; depending on its concentration it acts either to limit or to induce oxidative stress. The threshold concentration at which the pro-oxidant activity of DHEA prevails is not far in excess of that having an antioxidant effect. Either effect of DHEA on lipid peroxidation is only evident after a 'lag-phase'.

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