Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF-β signaling pathways in carbon tetrachloride (CCl<sub>4</sub>)-induced liver fibrosis in rats

Mohseni, Roohollah; Karimi, Jamshid; Tavilani, Heidar; Khodadadi, Iraj; Hashemnia, Mohammad

doi:10.1080/08923973.2019.1566926

Cited by 36 publications

(15 citation statements)

References 29 publications

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“…Previous studies have shown that CCl4 injection is associated with fibrosis, decreased body weight, and enhanced liver weight in rats. Consistent with the present findings, CAR treatment helped to prevent body weight loss following CCl4 exposure [39]. In contrast, administration of ibuprofen for 28 days decreased body weight compared to healthy rats, showing a clear divergence from other models.…”

Section: Discussionsupporting

confidence: 90%

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats

Lee

Yeom

Shim

et al. 2020

Korean J Physiol Pharmacol

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Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 90%

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats

Lee

Yeom

Shim

et al. 2020

Korean J Physiol Pharmacol

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“…Interestingly, in our recent study, TAZ expression in the liver tissue with SS, consistent with changing the level of HH ligands, was significantly lower than that of the control group (9). In some previous studies, it was suggested that the induction of TAZ expression is not a common feature of chronic liver disorders, and its expression is largely limited to those that are associated with steatosis, inflammation, and fibrosis (19,20). In this regard, it was reported that inhibiting TAZ expression in hepatocytes leads to a reduction in the histological characteristics of NASH, along with a reduction in the expression of fibrogenic and inflammatory genes.…”

Section: Yap/taz Signaling Pathwaysupporting

confidence: 67%

Signaling in Simple Steatosis and Non-alcoholic Steatohepatitis Cirrhosis: TGF-β1, YAP/TAZ, and Hedgehog Pathway Activity

Mohagheghi

Khajehahmadi

Tavilani

2018

Avicenna J Med Biochem

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Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of fat in the liver tissue that is usually associated with metabolic disorders. Traditionally, the disease is regarded as a spectrum of pathological conditions ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH) and hepatic fibrosis with progression to cirrhosis. However, so far, there is no available explanation for the disease progression. Several signaling pathways such as transforming growth factor (TGF)-β, hedgehog (HH), and yes-associated protein 1 (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling are attributed to the NAFLD pathogenesis. TGF-β1 pathway component expression aligns with HH pathway ligands expression elevate in NASH cirrhosis while they decrease in SS. YAP and TAZ are two transcriptional co-activators from the Hippo signaling pathway. Similarly, the TAZ level (but not YAP1) is higher in NASH cirrhosis compared to SS. In addition, these three signaling pathways have little molecular similarity but their changes are totally similar in SS and NASH cirrhosis. The present review discusses the main changes in the expression of TGF-β, HH, and YAP/TAZ pathway components in SS and NASH cirrhosis. It is hoped that these data provide a better understanding of the mechanisms that underlie the pathophysiology of NAFLD.

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“…Other natural anti-adipogenic substances, like cyanidin and carvacrol, Pompei et al (2012) and Spalletta et al (2018) may also restrain adipose tissue fibrosis, as recently seen for liver fibrosis. In particular cyanidin has been proven to be effective in antagonizing the oxidative stress, the inflammatory response and HSC activation; while carvacrol has been found to be particularly successful in inhibiting the TGFβ signaling pathway, by downregulating not only the TGF-β levels but also the protein levels of the related Hippo cascade mediators such as TAZ and YAP (Cho et al, 2014;Jiang et al, 2015;Hussein et al, 2017;Mohseni et al, 2019). Blockade of these signaling pathways could inhibit EMT and ameliorate fat fibrosis, as well as the associated metabolic dysfunctions such as insulin resistance.…”

Section: Adipose Tissue Fibrosismentioning

confidence: 99%

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

Gregorio

Robuffo

Spalletta³

et al. 2020

Front. Cell Dev. Biol.

102

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Fibrosis is a chronic and progressive disorder characterized by excessive deposition of extracellular matrix, which leads to scarring and loss of function of the affected organ or tissue. Indeed, the fibrotic process affects a variety of organs and tissues, with specific molecular background. However, two common hallmarks are shared: the crucial role of the transforming growth factor-beta (TGF-β) and the involvement of the inflammation process, that is essential for initiating the fibrotic degeneration. TGF-β in particular but also other cytokines regulate the most common molecular mechanism at the basis of fibrosis, the Epithelial-to-Mesenchymal Transition (EMT). EMT has been extensively studied, but not yet fully explored as a possible therapeutic target for fibrosis. A deeper understanding of the crosstalk between fibrosis and EMT may represent an opportunity for the development of a broadly effective anti-fibrotic therapy. Here we report the evidences of the relationship between EMT and multi-organ fibrosis, and the possible therapeutic approaches that may be developed by exploiting this relationship.

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Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF-β signaling pathways in carbon tetrachloride (CCl₄)-induced liver fibrosis in rats

Cited by 36 publications

References 29 publications

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats

Signaling in Simple Steatosis and Non-alcoholic Steatohepatitis Cirrhosis: TGF-β1, YAP/TAZ, and Hedgehog Pathway Activity

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

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Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF-β signaling pathways in carbon tetrachloride (CCl4)-induced liver fibrosis in rats

Cited by 36 publications

References 29 publications

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats

Signaling in Simple Steatosis and Non-alcoholic Steatohepatitis Cirrhosis: TGF-β1, YAP/TAZ, and Hedgehog Pathway Activity

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

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Product

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Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF-β signaling pathways in carbon tetrachloride (CCl₄)-induced liver fibrosis in rats