Emodin reverses CCl<sub>4</sub> induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The <i>in vivo</i> evidence

Bhadauria, Monika; Nirala, Satendra Kumar; Shrivastava, Sadhana; Sharma, Abhilasha; Johri, Sonia; Chandan, B. K.; Singh, B.; Saxena, Ajit Kumar; Shukla, Sangeeta

doi:10.1111/j.1872-034x.2008.00380.x

Cited by 22 publications

(7 citation statements)

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“…Lee et al demonstrated that emodin might be valuable for the protection of CCl 4 ‐induced liver injury by reducing lipid peroxidation and by positively modulating inflammation (Lee et al ., ). Emodin also had the ability to prevent CCl 4 ‐induced liver damage through reversing hepatic oxidative insults, CYP enzymatic activity and ultrastructural changes (Bhadauria et al ., ). In addition, emodin at a dose of 30 mg/kg (po) possessed optimum hepatoprotective ability against acetaminophen (APAP)‐induced toxicity via diminishing oxidative stress (Bhadauria, ).…”

Section: Pharmacologymentioning

confidence: 97%

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Dong

Yin

et al. 2016

Phytotherapy Research

569

365

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Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum. Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations. Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation. This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Pharmacologymentioning

confidence: 97%

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Dong

Yin

et al. 2016

Phytotherapy Research

569

365

View full text Add to dashboard Cite

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“…In addition, emodin and scopoletin are not P-gp substrates [ 45 , 46 ], so it would not be reduced because of the change of P-gp. Moreover emodin can also reverse CCl 4 -induced hepatic CYP enzymatic of hepatic drug-metabolizing enzymes [ 47 ], which could partly explain unchanged pharmacokinetic behavior. The causes and effects of the pharmacokinetic changes of components in YCHT still need further investigation.…”

Section: Resultsmentioning

confidence: 99%

Development and Application of an UHPLC‐MS/MS Method for Comparative Pharmacokinetic Study of Eight Major Bioactive Components from Yin Chen Hao Tang in Normal and Acute Liver Injured Rats

Wang

Xing

Cao

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Yin Chen Hao Tang (YCHT) is one of the most famous hepatoprotective herbal formulas in China, but its pharmacokinetic investigation in model rats has been rarely conducted. In this study, the hepatic injury model was caused by intraperitoneal injections of carbon tetrachloride (CCl4), and YCHT was orally administered to the model and normal rats. An ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was established to analyze the plasma pharmacokinetics of eight major bioactive ingredients from YCHT in both the normal and liver injured rats. The calibration curves presented good linearity (r > 0.9981) in the concentration range. The relative standard deviation (RSD%) of inter- and intraday precision was within 9.55%, and the accuracy (RE%) ranged from -10.72% to 2.46%. The extraction recovery, matrix effect, and stability were demonstrated to be within acceptable ranges. The lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were around 0.1 ng/mL and 0.5 ng/mL, respectively, which were much lower than those in other related researches. Results reveal that there are significant differences in the pharmacokinetics of scoparone, geniposide, rhein, aloe-emodin, physcion, and chrysophanol in hepatic injured rats as compared to those in control except for scopoletin and emodin. Our experimental results provide a meaningful reference for the clinical dosage of YCHT in treating liver disorders, and the improvement of LLOD and LLOQ can also broaden the range of our method's application, which is very suitable for quantitating these eight compounds with low levels.

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“…The histological observations in the present study were consistent with these previous results, which indicated the protective effect of Sal B on mice against the liver injury induced by CCl 4 ; 30 mg/kg Sal B had a strong protective effect on acute and chronic liver injury. Hepatocellular damage can be triggered by CCl 4 and the CYP450 enzyme system is predominantly responsible for the metabolism of CCl 4 to form free radicals (35). Highly reactive radicals generated from CCl 4 , such as trichloromethyl and trichloromethyl peroxyl, which destroy the respiratory chain on the mitochondrial membrane (36), then accumulate ROS in the cells to produce oxidative stress (37).…”

Section: Discussionmentioning

confidence: 99%

Salvianolic acid B protects against acute and chronic liver injury by inhibiting Smad2C/L phosphorylation

et al. 2021

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Salvianolic acid B (Sal B) has strong antioxidant and anti-fibrosis effects, which are related to the transforming growth factor β/Smad signaling pathway. However, how Sal B affects this antioxidant pathway and the phosphorylation (p-) of Smad2 at both the COOH-terminal (pSmad2C) and linker region (pSmad2L) are unknown. The aims of the present study were to investigate the underlying mechanisms of Sal B on acute and chronic liver injury induced by CCl 4 and H 2 O 2 , and its effects on p-Smad2C/L. In in vivo experiments, acute and chronic liver injury models were induced by CCl 4 , and the oxidative damage cell model was established in vitro with H 2 O 2. Liver histopathology was assessed using hematoxylin and eosin and Van Gieson's staining. Moreover, serum biochemical indicators were analyzed using specific assay kits. Furthermore, the present study evaluated the oxidant/antioxidant status in acute and chronic liver injury models by oxidative stress parameters such as malondialdehyde, glutathione and superoxide dismutase. In addition, western blot analysis was performed to analyze the protein expression levels of pSmad2C, pSmad2L, nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). It was found that Sal B improved liver histology, decreased the levels of aminotransferase and attenuated oxidative stress in acute and chronic liver injury models. Additionally, the protein expression levels of pSmad2C and pSmad2L were decreased, but Nrf2 and HO-1 expression levels were increased both in vivo and in vitro. Collectively, the present results suggested that Sal B may protect against acute and chronic liver injury via inhibition of Smad2C/L phosphorylation, and the Nrf2/HO-1 signaling pathway may play an important role in this process.

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Emodin reverses CCl₄ induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence

Abstract: By reversal CYP activity and ultrastructural changes, emodin shows a strong hepatoprotective abilities.

Cited by 22 publications

References 35 publications

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Development and Application of an UHPLC‐MS/MS Method for Comparative Pharmacokinetic Study of Eight Major Bioactive Components from Yin Chen Hao Tang in Normal and Acute Liver Injured Rats

Salvianolic acid B protects against acute and chronic liver injury by inhibiting Smad2C/L phosphorylation

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Emodin reverses CCl4 induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence

Abstract: By reversal CYP activity and ultrastructural changes, emodin shows a strong hepatoprotective abilities.

Cited by 22 publications

References 35 publications

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Emodin: A Review of its Pharmacology, Toxicity and Pharmacokinetics

Development and Application of an UHPLC‐MS/MS Method for Comparative Pharmacokinetic Study of Eight Major Bioactive Components from Yin Chen Hao Tang in Normal and Acute Liver Injured Rats

Salvianolic acid B protects against acute and chronic liver injury by inhibiting Smad2C/L phosphorylation

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Emodin reverses CCl₄ induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence