Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice

Jiang, Wenping; Huang, Shyh-Shyun; Matsuda, Yoshikazu; Saitō, Hiroshi; Uramaru, Naoto; Ho, Hui-Ya; Wu, Jin‐Bin; Huang, Guan‐Jhong

doi:10.3390/molecules22050830

Cited by 35 publications

(31 citation statements)

References 59 publications

(76 reference statements)

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“…The increase of the liver enzymes by high dose of paracetamol is similar to findings of other studies [ 5 20 ]. As albumin is mainly synthesized in the liver, the reduction of serum albumin and total protein by paracetamol overdose is another indication of liver injury.…”

Section: Discussionsupporting

confidence: 91%

Evaluation of antiproteinuric and hepato-renal protective activities of propolis in paracetamol toxicity in rats

Menyiy

Al-Waili

et al. 2018

Nutr Res Pract

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BACKGROUND/OBJECTIVESPropolis has a rich source of bioactive compounds and has renal and hepatic protective properties. The purpose of this study was to investigate the beneficial effect of hydro-ethanolic extract of propolis against paracetamol-induced liver damage and impairment of kidney function, as well as hematological changes in rats.MATERIALS AND METHODSSix groups of rats were used; the first group was served as a control; the second and third groups were treated by propolis extract at a dose of 50 and 100 mg/kg.B.WT. respectively; the fourth group was treated by paracetamol (200 mg/kg.B.WT.); the fifth group was treated by propolis (50 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days; and the sixth group was treated with propolis (100 mg/kg.B.WT.) for eight days and then received similar dose of propolis for following seven days with paracetamol at a dose of 200 mg/kg.B.WT. daily for the seven days. All the animals were treated for a period of 15 days. At the end of the experimental period, blood samples were collected for measurement of the liver enzymes, serum albumin, protein and creatinine, blood urea nitrogen, hematological parameters, and urine volume, protein and albumin.RESULTSParacetamol over dose significantly lowered hemoglobin, serum total protein, albumin, and uric acid, while it significantly increased blood creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, white blood cells, and platelet count as compared to the control. However, these alterations were significantly attenuated by the use of propolis extract and the effect was dose dependent. Interestingly, propolis prevented paracetamol induced proteinuria, low hemoglobin and body weight loss.CONCLUSIONSPropolis significantly prevented paracetamol induced renal, hepatic and hematological toxicity and might be useful in the management of liver and renal diseases particularly proteinuria.

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Section: Discussionsupporting

confidence: 91%

Evaluation of antiproteinuric and hepato-renal protective activities of propolis in paracetamol toxicity in rats

Menyiy

Al-Waili

et al. 2018

Nutr Res Pract

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“…The MAPK pathway consists of three routes viz extracellular regulated kinase (ERK), JNK, and p38MAPK. It is reported that the MAPK pathway is involved in the expression of NF- κ B in the nuclei and subsequent cytokine proteins such as iNOS and COX-2 as well as the pro-inflammatory cytokines such as TNF- α , IL-6, and IL-1 β [ 35 ]. Thus, the effect of Ugonin M on the phosphorylation of ERK, JNK, and p38MAPK was further evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…HO-1 serves as a rate-limiting enzyme that catalyzes heme to antioxidant and anti-inflammatory substances viz biliverdin, carbon monoxide, and iron and subsequently ameliorates symptoms of APAP-induced liver injury [ 35 , 43 ]. The expression of HO-1 will rapidly be up-regulated by oxidative stress conditions such as the administration of APAP [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Further, a previous report showed that COX-2, but not COX-1, was induced in livers of APAP-treated mice. There was an association of oxidative stress and inflammation in APAP-induced hepatotoxicity [ 35 , 46 ]. The results of this study discovered that Ugonin M could down-regulate the level of COX-2 and pro-inflammatory cytokines including TNF- α , IL-6, and IL-1 β , indicating that Ugonin M could mitigate the inflammatory response induced by APAP ( Figure 6 and Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

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Hepatoprotective Effect of Ugonin M, A Helminthostachys zeylanica Constituent, on Acetaminophen-Induced Acute Liver Injury in Mice

Kuo

et al. 2018

Molecules

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The present study aimed to discover the possible effectiveness of Ugonin M, a unique flavonoid isolated from Helminthostachys zeylanica—a traditional Chinese medicine used as anti-inflammatory medicine—and to elucidate the potential mechanisms of Ugonin M in the acute liver injury induced by acetaminophen (APAP). In this study, Ugonin M significantly ameliorated APAP-induced histopathological changes and the typical liver function biomarkers (i.e., alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (T-Bil)). It also affected APAP-induced abnormal lipid metabolism including total cholesterol (TC) and triglyceride (TG) in the serum. In inflammatory pharmacological action, Ugonin M suppressed the pro-inflammatory mediators such as nitric oxide (NO) and the lipid peroxidation indicator malondialdehyde (MDA). In addition, Ugonin M reinforced hemeoxygenase-1 (HO-1) protein expression and the production of antioxidant enzymes viz superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). Furthermore, inflammation-associated cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β as well as proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were decreased by the pretreatment of Ugonin M. Moreover, this study found that pretreatment of Ugonin M apparently decreased nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation via inhibition of the degradation of NF-κB, inhibitory κB-α (IκB-α), extracellular regulated kinase (ERK), c-Jun-N-terminal (JNK), and p38 active phosphorylation. In conclusion, Ugonin M significantly showed a protective effect against APAP-induced liver injury by reducing oxidative stress and inflammation. Thus, Ugonin M could be one of the effective components of H. zeylanica that plays a major role in the treatment of inflammatory disorders.

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“…for 6 days ICR mice, 400 mg/kg i.p. ↑SOD, CAT and GPx;↓NO, TNF-α, IL-1β [52] Methanol extract of Dicranopteris linearis L. leaves 50–500 mg/kg p.o. for 7 days Sprague-Dawley rats, 3 g/kg ↑SOD, CAT [132] Methanol extract of black ginseng 300–600 mg/kg i.g.…”

Section: Targeting Mitochondrial Oxidative Stress and Dysfunction Formentioning

confidence: 99%

Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions

et al. 2018

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Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed. To this end, it is necessary to better understand the mechanisms of APAP hepatotoxicity. Up to now, in addition to mitochondrial oxidative stress, many other cellular processes, including phase I/phase II metabolism, endoplasmic reticulum stress, autophagy, sterile inflammation, microcirculatory dysfunction, and liver regeneration, have been identified to be involved in the pathogenesis of AILI, providing new targets for developing more effective therapeutic interventions against APAP-induced liver injury. In this review, we summarize intracellular and extracellular events involved in APAP hepatotoxicity, along with emphatic discussions on the possible therapeutic approaches targeting these different cellular events.

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Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice

Cited by 35 publications

References 59 publications

Evaluation of antiproteinuric and hepato-renal protective activities of propolis in paracetamol toxicity in rats

Evaluation of antiproteinuric and hepato-renal protective activities of propolis in paracetamol toxicity in rats

Hepatoprotective Effect of Ugonin M, A Helminthostachys zeylanica Constituent, on Acetaminophen-Induced Acute Liver Injury in Mice

Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions

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