Herbal medicines for the liver: from bench to bedside

Vargas-Pozada, Eduardo E.; Muriel, Pablo

doi:10.1097/meg.0000000000001485

Cited by 11 publications

(6 citation statements)

References 95 publications

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“…Moreover, decreased mortality in alcohol-and nonalcohol-induced cirrhosis patients treated with silibinin was reported [75]. Thus, evidence indicates that ROS produced in response to chronic hepatic damage induced by various causes can trigger fibrogenesis and that antioxidants, most of which originate from herbal medicines, are effective in preventing and in some cases reverting liver fibrosis [4,76].…”

Section: Attenuating Oxidative Stress Produces An Antifibrotic Effectmentioning

confidence: 99%

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Ramos‐Tovar¹,

2020

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Activated hepatic stellate cells (HSCs) and myofibroblasts are the main producers of extracellular matrix (ECM) proteins that form the fibrotic tissue that leads to hepatic fibrosis. Reactive oxygen species (ROS) can directly activate HSCs or induce inflammation or programmed cell death, especially pyroptosis, in hepatocytes, which in turn activates HSCs and fibroblasts to produce ECM proteins. Therefore, antioxidants and the nuclear factor E2-related factor-2 signaling pathway play critical roles in modulating the profibrogenic response. The master proinflammatory factors nuclear factor-κB (NF-κB) and the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome may coordinate to produce and activate profibrogenic molecules such as interleukins 1β and 18, which effectively activate HSCs, to produce large amounts of fibrotic proteins. Furthermore, the NLRP3 inflammasome activates pro-caspase 1, which is upregulated by NF-κB, to produce caspase 1, which induces pyroptosis via gasdermin and the activation of HSCs. ROS play central roles in the activation of the NF-κB and NLRP3 signaling pathways via IκB (an inhibitor of NF-κB) and thioredoxin-interacting protein, respectively, thereby linking the molecular mechanisms of oxidative stress, inflammation and fibrosis. Elucidating these molecular pathways may pave the way for the development of therapeutic tools to interfere with specific targets.

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Section: Attenuating Oxidative Stress Produces An Antifibrotic Effectmentioning

confidence: 99%

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Ramos‐Tovar¹,

2020

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“…On the other hand, increasing evidence indicates that caffeine can protect the liver from various types of acute and chronic damage (Arauz et al 2017;Ramos-Tovar and Muriel 2019;Vargas-Pozada and Muriel 2020). Previous studies have suggested that caffeine may have therapeutic potential against NASH; however, no studies have demonstrated the efficacy of caffeine in this disease, and its mechanism of action is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

The antioxidant and anti-inflammatory activities of caffeine effectively attenuate nonalcoholic steatohepatitis and thioacetamide-induced hepatic injury in male rats

Vargas-Pozada

Ramos‐Tovar²,

Acero-Hernández

et al. 2023

Can. J. Physiol. Pharmacol.

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The antioxidant effect of caffeine, associated with its ability to upregulate the nuclear factor-E2-related factor-2 (Nrf2)-signaling pathway, was explored as a possible mechanism for the attenuation of liver damage. Nonalcoholic steatohepatitis (NASH) was induced in rats by the administration of a high-fat, high-sucrose, high-cholesterol diet (HFSCD) for 15 weeks. Liver damage was induced in rats by intraperitoneal administration of thioacetamide (TAA) for six weeks. Caffeine was administered orally at a daily dose of 50 mg/kg body weight during the period of NASH induction to evaluate its ability to prevent disease development. Meanwhile, rats received TAA for three weeks, after which 50 mg/kg caffeine was administered daily for three weeks with TAA to evaluate its capacity to interfere with the progression of hepatic injury. HFSCD administration induced hepatic steatosis, decreased Nrf2 levels, increased oxidative stress, induced the activation of nuclear factor-κB (NF-κB), and elevated proinflammatory cytokine levels, leading to hepatic damage. TAA administration produced similar effects, excluding steatosis. Caffeine increased Nrf2 levels; attenuated oxidative stress markers, including malondialdehyde and 4-hydroxynonenal; restored normal, reduced glutathione levels; and reduced NF-κB activation, inflammatory cytokine levels, and damage. Our findings suggest that caffeine may be useful in the treatment of human liver diseases.

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“…The NLRP3 inflammasome plays a pivotal role in NASH progression [ 8 ], making it an attractive target for the treatment of NASH. Caffeine has been shown to protect the liver from acute and chronic damage of diverse etiologies through antioxidant, anti-inflammatory, antifibrotic, and antisteatotic mechanisms [ 8 , 9 , 12 ]. However, the role of caffeine in the NLRP3 inflammasome signaling pathway had not yet been investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Caffeine is a natural compound with beneficial effects on the liver [ 12 , 13 ]. Caffeine administration to experimental animals ameliorates liver scar tissue deposition, and frequent coffee consumption may reduce hepatic injury in patients with NASH [ 14 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Caffeine Inhibits NLRP3 Inflammasome Activation by Downregulating TLR4/MAPK/NF-κB Signaling Pathway in an Experimental NASH Model

Vargas-Pozada

Ramos‐Tovar²,

Rodríguez-Callejas

et al. 2022

IJMS

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Caffeine elicits protective effects against liver diseases, such as NASH; however, its mechanism of action involving the pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway remains to be elucidated. This study aimed to evaluate the effect of caffeine on the NLRP3 inflammasome signaling pathway in a rat model of NASH. NASH was induced by feeding rats a high-fat, -sucrose, and -cholesterol diet (HFSCD) for 15 weeks along with a weekly low dose (400 mg/kg, i.p.) of CCl4. Caffeine was administered at 50 mg/kg p.o. The effects of HFSCD+CCl4 and caffeine on the liver were evaluated using biochemical, ultrastructural, histological, and molecular biological approaches. The HFSCD+CCl4-treated rats showed fat accumulation in the liver, elevated levels of inflammatory mediators, NLRP3 inflammasome activation, antioxidant dysregulation, and liver fibrosis. Caffeine reduced necrosis, cholestasis, oxidative stress, and fibrosis. Caffeine exhibited anti-inflammatory effects by attenuating NLRP3 inflammasome activation. Moreover, caffeine prevented increases in toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) protein levels and mitigated the phosphorylation of mitogen-activated protein kinase (MAPK). Importantly, caffeine prevented the activation of hepatic stellate cells. This study is the first to report that caffeine ameliorates NASH by inhibiting NLRP3 inflammasome activation through the suppression of the TLR4/MAPK/NF-κB signaling pathway.

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Herbal medicines for the liver: from bench to bedside

Cited by 11 publications

References 95 publications

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver

The antioxidant and anti-inflammatory activities of caffeine effectively attenuate nonalcoholic steatohepatitis and thioacetamide-induced hepatic injury in male rats

Caffeine Inhibits NLRP3 Inflammasome Activation by Downregulating TLR4/MAPK/NF-κB Signaling Pathway in an Experimental NASH Model

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