Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity

Wang, Kunpeng; Bai, Yu; Wang, Jian; Zhang, Jin-Zhen

doi:10.3892/mmr.2014.2004

Cited by 11 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MAPKs, including ERK, JNK and p38, are part of the IGF-IR signaling pathway and convert extracellular stimuli into a wide range of cellular responses. These proteins serve important roles in cell proliferation, differentiation, metabolism, survival and death (87,88), as well as in oxidative damage (77,78). JNK is primarily involved apoptosis and is activated by oxidative damage, whereas ERK regulates cell growth and differentiation, is activated by oxidative damage, and acts as a cell death suppression signal to maintain homeostasis (89).…”

Section: Discussionmentioning

confidence: 99%

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

2019

View full text Add to dashboard Cite

Acetaminophen (APAP) is a widely used analgesic and antipyretic. It is safe at normal treatment doses; however, APAP overdose is a major cause of acute liver and kidney failure. A variety of methods to reduce the damage caused by APAP overdose have previously been evaluated. The protein-rich seaweed Pyropia yezoensis has antioxidant, antitumor and anti-inflammatory activities, and protects against cytotoxicity. However, little is known regarding the protective effects of P. yezoensis peptide against APAP-induced hepatotoxicity. The present study investigated the ability of P. yezoensis peptide (PYP1-4) to ameliorate the damage caused by APAP-induced hepatotoxicity using HepG2 as the model cell line in addition to the signaling pathways involved. Briefly, cell viability, nitric oxide, reactive oxygen species and apoptosis assays were performed in conjunction with western blot analysis and reverse transcription-quantitative PCR. First, the present study revealed the minimum toxic concentration of APAP (15 mM) and the resting concentration of PYP1-4 (0-500 ng/ml). Administration of PYP1-4 to APAP-induced cells decreased the nitric oxide and reactive oxygen species levels, and restored the levels of antioxidant-associated proteins (catalase, heme oxygenase 1, superoxide dismutase 2 and quinone oxidoreductase 1). PYP1-4 increased the translocation of nuclear factor, erythroid 2 like 2 to the nucleus and the activities of glycogen synthase kinase-3β, Akt and AMP-activated protein kinase. In addition, APAP induced apoptosis; however, PYP1-4 inhibited apoptosis by modulating the levels of pro-apoptotic markers (Bad), anti-apoptotic markers (Bcl-2 and BH3 interacting domain death agonist), caspases and poly (ADP-ribose) polymerase 1. Subsequently, the insulin-like growth factor 1 receptor signaling pathway was investigated to determine whether PYP1-4 treatment restored the levels of cell growth-associated factors during APAP-induced hepatotoxicity. PYP1-4 treatment impacted the levels of components of the insulin receptor substrate 1/PI3K/Akt and Ras/Raf/ERK signaling pathways, and promoted cell survival. Therefore, the P. yezoensis peptide PYP1-4 may be useful for preventing APAP-induced hepatotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

2019

View full text Add to dashboard Cite

show abstract

“…Recently evidence has been accumulated that those side effects like nephrotoxicity and hepatotoxicity are closely related to the activity of reactive oxygen species (ROS) (Gurocak et al, 2013;Rodrigues et al, 2014;Wang et al, 2014). ROS including superoxide anion radical (O 2 ·-), hydroxyl radical (·OH), hydrogen peroxide (H 2 O 2 ), singlet oxygen ( 1 O 2 ) and nitric oxide (NO), which are directly involved in oxidative damage of cellular macromolecules such as lipids, proteins and nucleic acids in tissues.…”

Section: Introductionmentioning

confidence: 99%

Pu-erh Tea Powder Preventive Effects on Cisplatin-Induced Liver Oxidative Damage in Wistar Rats

Zheng¹,

Wang²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Asian Pac J Cancer Prev, 15 (17), 7389-7394 IntroductionChemotherapy is one of the major means for malignancy. It seeks to shrink tumors, decrease cancerrelated symptoms, advance quality of life, lengthen life spans of patients, and so on. Many studies have shown the effectiveness and feasibility of chemotherapy for cancers species involving the lung, pancreas, liver, large intestine, and so on. Conversely, treatment with anticancer drugs can also do harm to patients' normal tissues and organs, and those toxicities may lead to a worsened quality of life and shortened survival.Cisplatin (cis-diamminedichloroplatinumⅡ, CDDP) is one of the main chemotherapeutics, which is widely used for the treatment of various malignant solid tumors such as ovarian, lung, testicular and head and neck cancers (Pfister et al., 2010;Dimri et al., 2013; Dua et al., 2013;Besse et al., 2014 AbstractBackground: Chemotherapy is one of the major means for control of malignancies, with cisplatin (CDDP) as one of the main agents, widely used for the treatment of various malignant solid tumors. However, prevention of hepatotoxicity from cisplatin is one of the urgent issues in cancer chemotherapy. In this study, we aimed to investigate the effects of pu-erh tea on hepatotoxicity through body weight and tissue antioxidant parameters like, liver coefficient, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde(MDA) and glutathione (GSH) levels, and light microscopic evaluation by histological findings. Materials and Methods: The rats were randomly divided into five groups: Control (n=10), cisplatin (3 mg/kg p.i., n=10), cisplatin+pu-erh (0.32 g/kg/day i.g., n=10), cisplatin+pu-erh (0.8 g/kg/day i.g., n=10) and cisplatin+pu-erh (1.6 g/kg/day i.g., n=10). Pu-erh tea powder was administrated for 31 consecutive days. The rats were sacrificed at the end on the second day after a single dose of cisplatin treatment for measuring indices. Results: Pu-erh tea powder exhibited a protective effect by decreasing MDA and GSH and increasing the SOD and GSH-PX levels and GSH-PX/MDA ratio in camparison with the control group. Besides, pu-erh tea was also able to alleviate the pathological damage to some extent. Conclusion: Pu-erh tea powder is protective against cisplatin-induced liver oxidative damages, especially at the medium dosage (0.8 g/kg/d).

show abstract

“…Recently, it has been reported that inhibition of c-Jun N-terminal kinase signaling pathway is involved in the liver protective effect of SCE in mice with acetaminophen-induced liver injury. 59 Moreover, SCE or its components can inhibit nuclear transcription factor-κB and mitogen-activated protein kinase signaling pathways, contributing to its beneficial effects. 80 , 83 , 84 Moreover, the RNA interfering efficiency may change, contributing to these varying effects.…”

Section: Discussionmentioning

confidence: 99%

“…Previous preclinical studies have found that SCE and its major active lignanoids protected the liver in various liver-injured models, with different mechanisms involved in its hepatoprotective activities. 43 – 59 These include antioxidation, inhibition of cytokine production, inhibition of apoptosis, activation of Nrf2, and other possible mechanisms. 51 – 59 However, the mechanism is not fully understood, and the role of Nrf2 in the hepatoprotection of SCE is not elucidated.…”

Section: Introductionmentioning

confidence: 99%

“… 43 – 59 These include antioxidation, inhibition of cytokine production, inhibition of apoptosis, activation of Nrf2, and other possible mechanisms. 51 – 59 However, the mechanism is not fully understood, and the role of Nrf2 in the hepatoprotection of SCE is not elucidated. In this study, we aimed to examine the role of Nrf2 in the modulating effects of SCE on important DMEs and drug transporters in human hepatocellular liver carcinoma (HepG2) cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway

Zhou

Yin

et al. 2014

DDDT

View full text Add to dashboard Cite

Drug metabolizing enzymes (DMEs) and drug transporters are regulated via epigenetic, transcriptional, posttranscriptional, and translational and posttranslational modifications. Phase I and II DMEs and drug transporters play an important role in the disposition and detoxification of a large number of endogenous and exogenous compounds. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a critical regulator of a variety of important cytoprotective genes that are involved in disposition and detoxification of xenobiotics. Schisandra chinensis (SC) is a commonly used traditional Chinese herbal medicine that has been primarily used to protect the liver because of its potent antioxidative and anti-inflammatory activities. SC can modulate some DMEs and drug transporters, but the underlying mechanisms are unclear. In this study, we aimed to explore the role of Nrf2 in the regulatory effect of SC extract (SCE) on selected DMEs and drug transporters in human hepatocellular liver carcinoma cell line (HepG2) cells. The results showed that SCE, schisandrin A, and schisandrin B significantly increased the expression of NAD(P)H: Nicotinamide Adenine Dinucleotide Phosphate-oxidase or:quinone oxidoreductase 1, heme oxygenase-1, glutamate–cysteine ligase, and glutathione S-transferase A4 at both transcriptional and posttranscriptional levels. Incubation of HepG2 cells with SCE resulted in a significant increase in the intracellular level of glutathione and total glutathione S-transferase content. SCE significantly elevated the messenger ribonucleic acid and protein levels of P-glycoprotein and multidrug resistance-associated protein 2 and 4, whereas the expression of organic anion transporting peptide 1A2 and 1B1 was significantly downregulated by SCE. Knockdown of Nrf2 by small interfering ribonucleic acid attenuated the regulatory effect of SCE on these DMEs and drug transporters. SCE significantly upregulated Nrf2 and promoted the translocation of Nrf2 from cytoplasm to the nuclei. Additionally, SCE significantly suppressed the expression of cytosolic Kelch-like ECH-associated protein 1 (the repressor of Nrf2) and remarkably increased Nrf2 stability in HepG2 cells. Taken together, our findings suggest that the hepatoprotective effects of SCE may be partially ascribed to the modulation of DMEs and drug transporters via Nrf2-mediated signaling pathway. SCE may alter the pharmacokinetics of other coadministered drugs that are substrates of these DMEs and transporters and thus cause unfavorable herb–drug interactions.

show abstract

Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity

Cited by 11 publications

References 27 publications

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

Pu-erh Tea Powder Preventive Effects on Cisplatin-Induced Liver Oxidative Damage in Wistar Rats

Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway

Contact Info

Product

Resources

About

Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity

Cited by 11 publications

References 27 publications

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

Pu-erh Tea Powder Preventive Effects on Cisplatin-Induced Liver Oxidative Damage in Wistar Rats

Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of&nbsp;Nrf2-mediated signaling pathway

Contact Info

Product

Resources

About

Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway