scholarly journals Drug-Drug Interaction Potential, Cytotoxicity, and Reactive Oxygen Species Production of Salix Cortex Extracts Using Human Hepatocyte-Like HepaRG Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
João Victor Dutra Gomes ◽  
Corinna Herz ◽  
Simone Helmig ◽  
Nadja Förster ◽  
Inga Mewis ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Enzyme Activity ◽  
Drug Interaction ◽  
Drug Interactions ◽  
Interaction Potential ◽  
Reactive Oxygen ◽  
Human Hepatocyte ◽  
Oxygen Species ◽  
Heparg Cells ◽  
Cyp450 Enzyme

Herbal preparations of willow bark (Salix cortex) are available in many countries as non-prescription medicines for pain and inflammation, and also as dietary supplements. Currently only little information on toxicity and drug interaction potential of the extracts is available. This study now evaluated the effects of two Salix cortex extracts on human hepatocyte-like HepaRG cells, in view of clinically relevant CYP450 enzyme activity modulation, cytotoxicity and production of reactive oxygen species (ROS). Drug metabolism via the CYP450 enzyme system is considered an important parameter for the occurrence of drug-drug interactions, which can lead to toxicity, decreased pharmacological activity, and adverse drug reactions. We evaluated two different bark extracts standardized to 10 mg/ml phenolic content. Herein, extract S6 (S. pentandra, containing 8.15 mg/ml total salicylates and 0.08 mg/ml salicin) and extract B (industrial reference, containing 5.35 mg/ml total salicylates and 2.26 mg/ml salicin) were tested. Both Salix cortex extracts showed no relevant reduction in cell viability or increase in ROS production in hepatocyte-like HepaRG cells. However, they reduced CYP1A2 and CYP3A4 enzyme activity after 48 h at ≥25 μg/ml, this was statistically significant only for S6. CYP2C19 activity inhibition (0.5 h) was also observed at ≥25 μg/ml, mRNA expression inhibition by 48 h treatment with S6 at 25 μg/ml. In conclusion, at higher concentrations, the tested Salix cortex extracts showed a drug interaction potential, but with different potency. Given the high prevalence of polypharmacy, particularly in the elderly with chronic pain, further systematic studies of Salix species of medical interest should be conducted in the future to more accurately determine the risk of potential drug interactions.

scholarly journals Vigor difference during storage and germination in Indian mustard explained by reactive oxygen species and antioxidant enzymes

2020 ◽  
Vol 44 (6) ◽  
pp. 577-588
Author(s):  
Nipa BISWAS ◽  
Sangita YADAV ◽  
Shiv Kumar YADAV ◽  
Ravish CHOUDHARY ◽  
Navinder SAINI ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Enzyme Activity ◽  
Erucic Acid ◽  
Antioxidant Enzyme ◽  
Indian Mustard ◽  
Reactive Oxygen ◽  
Antioxidant Enzyme Activity ◽  
Oxygen Species ◽  
Double Zero ◽  
Low Erucic Acid

Canola-type genotypes in Indian mustard (Brassica juncea) are a new kind of quality resource developed for their low levels of erucic acid (<2%) and glucosinolate (<30 μmole/g defatted meal) contents. Single-zero (low erucic acid) and double-zero (low erucic acid and glucosinolate content) genotypes of Indian mustard have less vigor. Conventional genotypes (high erucic acid and glucosinolate contents) havea significantly higher seedling vigor index-II (SVI-II) and single-zero genotypes have a significantly higher SVI-I, whereas double-zero genotypes have been observed to have a significantly lower SVI-I and SVI-II. To know the possible reasons for the differences in vigor, the seed quality parameters, reactive oxygen species (ROS) contents (superoxide radicals (O2−·) and hydrogen peroxide), lipid peroxidation, and antioxidant enzyme activity were examined. In the dry seeds, the conventional genotypes revealed lower ROS contents and higher catalase and peroxidase enzyme activity. This trend was reversed in the double-zero genotypes, which could be the reason why they were more susceptible to oxidative damage. During seed germination, an increase in the ROS contents, and corresponding increase in antioxidant enzyme activity, was noticed, which was highest in the conventional genotypes, followed by the single-zero genotypes. Double-zero genotypes showed the lowest increase in ROS contents and antioxidant enzyme activity during this period. This meant that the required attributes were met for maintaining oxidative balance within the cells and triggering physiological activities to reach high vigor. This study proposed 2 causes for the poor vigor of the double-zero genotypes; first, in the dry seeds, the ROS remained high due to low antioxidant activity (ROS scavengers) and the second was less generation of O2−· during germination.

Reactive oxygen species production and antioxidant enzyme activity during epididymal sperm maturation in Corynorhinus mexicanus bats

2016 ◽  
Vol 16 (1) ◽  
pp. 78-86 ◽  
Author(s):  
Arenas-Ríos Edith ◽  
Rosado García Adolfo ◽  
Cortés-Barberena Edith ◽  
Königsberg Mina ◽  
Arteaga-Silva Marcela ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Enzyme Activity ◽  
Antioxidant Enzyme ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Antioxidant Enzyme Activity ◽  
Sperm Maturation ◽  
Oxygen Species ◽  
Epididymal Sperm ◽  
Species Production

scholarly journals Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

2017 ◽  
Vol 42 (2) ◽  
pp. 685-696 ◽  
Author(s):  
Xiaoxv Dong ◽  
Jing Fu ◽  
Xingbin Yin ◽  
Changhai Qu ◽  
Chunjing Yang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Viability ◽  
Reactive Oxygen ◽  
Mitochondrial Pathway ◽  
Phase Cell ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Heparg Cell Line ◽  
Heparg Cells ◽  
Aloe Emodin

Background/Aims: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), an anthraquinone active compounds, is isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. The aim of this study was to determine potential cytotoxic effects of aloe-emodin on HepaRG cells and to define the underlying mechanism. Methods: MTT was used to evaluate cell viability. Apoptotic cell death was analyzed via Annexin V-FITC/PI double staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were determined by flow cytometry, while the expression of apoptosis-related proteins was determined by Western blot analysis. Results: Treatment with aloe-emodin significantly reduced cell viability and induced apoptosis in HepaRG cells in a dose- and time-dependent manner. It provoked ROS generation and depolarization of MMP in HepaRG cells when compared with controls. Aloe-emodin dose-dependently increased release of mitochondrial cytochrome c, and levels of Fas, p53, p21, Bax/Bcl-2 ratio, as well as activation of caspase-3, caspase-8, caspase-9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). It also induced S-phase cell cycle arrest by increasing the expression of p21 and cyclin E proteins while significantly decreasing the expression of cyclin A and CDK2. Conclusion: These results suggest that aloe-emodin inhibits cell proliferation and induces apoptosis in HepaRG cells, most probably through a mechanism involving both Fas death pathway and the mitochondrial pathway by generation of ROS. These findings underscore the need for risk assessment of human exposure to aloe-emodin.

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