4-O′-methylhonokiol protects from alcohol/carbon tetrachloride-induced liver injury in mice

Patsenker, E.; Chicca, Andrea; Petrucci, Vanessa; Moghadamrad, Sheida; Gottardi, Andrea De; Hampe, Jochen; Gertsch, Jürg; Semmo, Nasser; Stickel, Felix

doi:10.1007/s00109-017-1556-y

Cited by 6 publications

(5 citation statements)

References 53 publications

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“…Magnolol also attenuated ConA-induced liver fibrosis and suppressed human LX2 HSC activation, which was closely related to inhibiting Th17 cell differentiation by suppressing IL-17A generation [ 141 ]. In addition, other honokiol derivatives, such as 4′-O-methylhonokiol, also prevented from HSC activation and induced apoptosis via regulation of Bak1 and Bcl-2 expression [ 142 ].…”

Section: Lignansmentioning

confidence: 99%

A Comprehensive Review of Natural Products against Liver Fibrosis: Flavonoids, Quinones, Lignans, Phenols, and Acids

Pan

Jiang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Liver fibrosis resulting from continuous long-term hepatic damage represents a heavy burden worldwide. Liver fibrosis is recognized as a complicated pathogenic mechanism with extracellular matrix (ECM) accumulation and hepatic stellate cell (HSC) activation. A series of drugs demonstrate significant antifibrotic activity in vitro and in vivo. No specific agents with ideally clinical efficacy for liver fibrosis treatment have been developed. In this review, we summarized the antifibrotic effects and molecular mechanisms of 29 kinds of common natural products. The mechanism of these compounds is correlated with anti-inflammatory, antiapoptotic, and antifibrotic activities. Moreover, parenchymal hepatic cell survival, HSC deactivation, and ECM degradation by interfering with multiple targets and signaling pathways are also involved in the antifibrotic effects of these compounds. However, there remain two bottlenecks for clinical breakthroughs. The low bioavailability of natural products should be improved, and the combined application of two or more compounds should be investigated for more prominent pharmacological effects. In summary, exploration on natural products against liver fibrosis is becoming increasingly extensive. Therefore, natural products are potential resources for the development of agents to treat liver fibrosis.

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Section: Lignansmentioning

confidence: 99%

A Comprehensive Review of Natural Products against Liver Fibrosis: Flavonoids, Quinones, Lignans, Phenols, and Acids

Pan

Jiang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…In particular, the cannabinoid receptors CB1 and CB2 are upregulated in almost all chronic liver diseases, as well as cirrhosis and related disorders, and these receptors can be therapeutically antagonized[26-28]. Previous studies revealed that the CB2 agonists JWH-133 and 4′-O-methylhonokiol showed protective effects, such as decreased hepatocyte steatosis, inflammation, and liver regeneration[29-31]. In this study, we noted higher levels of CEA during the process of liver fibrosis, representing continuously increased concentrations of a CB2 agonist against CCl 4 -induced liver damage.…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes of key metabolites during liver fibrosis in rats

Chen

et al. 2019

WJG

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BACKGROUND Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease. Established non-invasive tests for monitoring fibrosis are lacking, and new biomarkers of liver fibrosis and function are needed. AIM To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis progression. METHODS CCl 4 was used to establish the rat liver fibrosis model. Liver fibrosis process was measured by liver chemical tests, liver histopathology, and Masson’s trichrome staining. The expression levels of two fibrotic markers including α-smooth muscle actin and transforming growth factor β1 were assessed using immunohistochemistry and real-time polymerase chain reaction. Dynamic changes in metabolic proﬁles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS To investigate the dynamic changes of metabolites during the process of liver fibrosis, sera from control and fibrosis model rats based on pathological results were analyzed at five different time points. We investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine, L-threonine, indoleacrylic acid, β-muricholic acid (β-MCA), cervonoyl ethanolamide (CEA), phosphatidylcholines, and lysophosphatidylcholines. Two metabolites, CEA and β-MCA, differed significantly in the fibrosis model rats compared to controls ( P < 0.05) and showed prognostic value for fibrosis. ROC curve analyses performed to calculate the area under the curve (AUC) revealed that CEA and β-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8, and can clearly differentiate early stage from late stage fibrosis or cirrhosis. CONCLUSION This study identified two novel biomarkers of fibrosis, CEA and β-MCA, which were effective for diagnosing fibrosis in an animal model.

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“…In highfat diet-fed mice, MHK prevents fibrosis, organ injury, and lipid accumulation in liver, heart, and kidney [101,184,185]. Remarkably, MHK significantly downregulated CB 1 R overexpression and increased the hepatic concentrations of several N-acetylethanolamines, including AEA, OEA, and PEA [186].…”

Section: Cb 2 R-pparγmentioning

confidence: 96%

Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System

Lago-Fernandez¹,

Zarzo-Arias²,

Jagerovic³

et al. 2021

IJMS

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Cannabinoids have shown to exert their therapeutic actions through a variety of targets. These include not only the canonical cannabinoid receptors CB1R and CB2R but also related orphan G protein-coupled receptors (GPCRs), ligand-gated ion channels, transient receptor potential (TRP) channels, metabolic enzymes, and nuclear receptors. In this review, we aim to summarize reported compounds exhibiting their therapeutic effects upon the modulation of CB1R and/or CB2R and the nuclear peroxisome proliferator-activated receptors (PPARs). Concomitant actions at CBRs and PPARα or PPARγ subtypes have shown to mediate antiobesity, analgesic, antitumoral, or neuroprotective properties of a variety of phytogenic, endogenous, and synthetic cannabinoids. The relevance of this multitargeting mechanism of action has been analyzed in the context of diverse pathologies. Synergistic effects triggered by combinatorial treatment with ligands that modulate the aforementioned targets have also been considered. This literature overview provides structural and pharmacological insights for the further development of dual cannabinoids for specific disorders.

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4-O′-methylhonokiol protects from alcohol/carbon tetrachloride-induced liver injury in mice

Cited by 6 publications

References 53 publications

A Comprehensive Review of Natural Products against Liver Fibrosis: Flavonoids, Quinones, Lignans, Phenols, and Acids

A Comprehensive Review of Natural Products against Liver Fibrosis: Flavonoids, Quinones, Lignans, Phenols, and Acids

Dynamic changes of key metabolites during liver fibrosis in rats

Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System

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