Caffeine in liver diseases: Pharmacology and toxicology

Abstract

We have previously shown that adenosine A1AR antagonists, adenosine A2aAR antagonists, and caffeine have significant inhibitory effects on the activation and proliferation of hepatic stellate cells in alcoholic liver fibrosis. Many recent studies have found that moderate coffee consumption is beneficial for various liver diseases. The main active ingredient of coffee is caffeine, which is a natural non-selective adenosine receptor antagonist. Moreover, numerous preclinical epidemiological studies and clinical trials have examined the association between frequent coffee consumption and the risk of developing different liver diseases. In this review, we summarize and analyze the prophylactic and therapeutic effects of caffeine on various liver diseases, with an emphasis on cellular assays, animal experiments, and clinical trials. To review the prevention and treatment effects of caffeine on different liver diseases, we searched all literature before 19 July 2022, using “caffeine” and “liver disease” as keywords from the PubMed and ScienceDirect databases. We found that moderate coffee consumption has beneficial effects on various liver diseases, possibly by inhibiting adenosine binding to its receptors. Caffeine is a potential drug for the prevention and treatment of various liver diseases.

Single cell G‐protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21

“…These findings complement an existing body of literature describing the roles of A 2A receptors in fibrogenesis (Herman‐de‐Sousa et al, 2022; Kim et al, 2022; Perez‐Aso et al, 2014; Shaikh et al, 2016; J. Zhang et al, 2017) and the effects of caffeine on tissue fibrosis. For instance, caffeine has been reported to inhibit the activation of BHK‐21 kidney fibroblasts induced by hypoxia (Nilnumkhum et al, 2019) and it has also been reported to attenuate fibrosis of the liver (Modi et al, 2010; Shan et al, 2022) and lungs (Tatler et al, 2016). Conversely, however, caffeine worsened fibrosis in a mouse model of cystic kidney disease (Meca et al, 2019), activation of A 2A receptors attenuated fibrosis in experimental glomerulonephritis (Garcia et al, 2011), and a dual‐acting A 2A receptor agonist and A 3A receptor antagonist (LJ‐4459) reduced tubulointerstitial fibrosis in UUO mice (Pak et al, 2021).…”

“…Zhang et al, 2017) and the effects of caffeine on tissue fibrosis. For instance, caffeine has been reported to inhibit the activation of BHK-21 kidney fibroblasts induced by hypoxia (Nilnumkhum et al, 2019) and it has also been reported to attenuate fibrosis of the liver (Modi et al, 2010;Shan et al, 2022) and lungs (Tatler et al, 2016).…”

Does caffeine have a double-edged sword role in inflammation and carcinogenesis in the colon?

“…Moderate coffee intake has been suggested to have beneficial effects (hepatoprotective effect) on various liver diseases, including alcoholic liver disease, 50 nonalcoholic fatty liver disease, 51,52 liver cirrhosis, 53 hepatitis caused by hepatitis B virus, 54 and hepatitis C virus, 55 possibly by inhibiting the binding of adenosine to its receptor. 56,57 Furthermore, espresso coffee has been shown to have no beneficial effect on liver disease, particularly nonalcoholic fatty liver disease. 58 This may be due to the effect of the addition of sucrose, which is composed of glucose and fructose, to the coffee, which may counteract the effect.…”

Current therapeutic targets and multifaceted physiological impacts of caffeine

“…Caffeine, which belongs to the methylxanthines family, exhibits dose‐dependent desirable effects at lower doses (≤400 mg), but shows adverse effects and health issues across multiple organ systems at concentrations higher than this dose of ingestion (Lopes et al, 2019; Shan et al, 2022). Thus, several mechanisms have been suggested for the caffeine pharmacological impact on various organs and systems, including antioxidant and anti‐inflammatory activities; some of the elucidated mechanisms or pathways adopted by caffeine to exhibit therapeutic potency in different diseases of the same organ via different receptors or pathways are also briefed in Table 2.…”