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Review
. 2024 Feb 3;29(3):709.
doi: 10.3390/molecules29030709.

Proanthocyanidins-Based Synbiotics as a Novel Strategy for Nonalcoholic Fatty Liver Disease (NAFLD) Risk Reduction

Wasitha P D W Thilakarathna  1 , H P Vasantha Rupasinghe  1   2
Affiliations
Review

Proanthocyanidins-Based Synbiotics as a Novel Strategy for Nonalcoholic Fatty Liver Disease (NAFLD) Risk Reduction

Wasitha P D W Thilakarathna et al. Molecules. .

Abstract

Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, is a spectrum of liver abnormalities ranging from steatosis to nonalcoholic steatohepatitis (NASH) characterized by excessive lipid accumulation. The prevalence of NAFLD is predicted to increase rapidly, demanding novel approaches to reduce the global NAFLD burden. Flavonoids, the most abundant dietary polyphenols, can reduce the risk of NAFLD. The majority of dietary flavonoids are proanthocyanidins (PACs), which are oligomers and polymers of the flavonoid sub-group flavan-3-ols. The efficacy of PAC in reducing the NAFLD risk can be significantly hindered by low bioavailability. The development of synbiotics by combining PAC with probiotics may increase effectiveness against NAFLD by biotransforming PAC into bioavailable metabolites. PAC and probiotic bacteria are capable of mitigating steatosis primarily through suppressing de novo lipogenesis and promoting fatty acid β-oxidation. PAC and probiotic bacteria can reduce the progression of steatosis to NASH mainly through ameliorating hepatic damage and inflammation induced by hepatic oxidative stress, endoplasmic reticulum stress, and gut microbiota dysbiosis. Synbiotics of PAC are superior in reducing the risk of NAFLD compared to independent administration of PAC and probiotics. The development of PAC-based synbiotics can be a novel strategy to mitigate the increasing incidence of NAFLD.

Keywords: flavonoids; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; proanthocyanidins; probiotic bacteria; steatosis; synbiotics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Hepatic lipid metabolism. ACC, acetyl-CoA carboxylase; ChREBP, carbohydrate response element-binding protein; FAS, fatty acid synthase; LPL, lipoprotein lipase; SREBP-1, sterol regulatory element binding protein-1; VLDL, very-low-density lipoprotein (created with BioRender.com, a license purchased, accessed on 14 November 2023).
Figure 2
Figure 2
Mechanisms of steatosis pathogenesis. The red arrows indicate the increased or decreased expression/production under hepatic steatosis. ACC, acetyl-CoA carboxylase; ACLY, adenosine triphosphate citrate lyase; CD36, cluster of differentiation 36; ChREBP, carbohydrate response element-binding protein; ER, endoplasmic reticulum; FAS, fatty acid synthase; FATP, fatty acid transport protein; FXR, farnesoid X receptor; GLUT4, glucose transporter type 4; LPS, lipopolysaccharide; LXR, liver X receptor; MAM, mitochondria-associated ER membrane; PPAR, peroxisome proliferator-activated receptor; p-PEPCK, phosphorylated phosphoenolpyruvate carboxylase; SREBP-1, sterol regulatory element binding protein-1 (created with BioRender.com, a license purchased, accessed on 14 November 2023).
Figure 3
Figure 3
Mechanisms of steatosis progression to nonalcoholic steatohepatitis. The red arrows indicate the increased or decreased expression/production under nonalcoholic steatohepatitis. ApoB, apolipoprotein B; ATF6α, activating transcription factor-6α; CCL2, C-C motif chemokine ligand 2; CD36, cluster of differentiation 36; CHOP, CCAAT-enhancer-binding protein-homologous protein; DAMPs, damage-associated molecular patterns; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; FXR, farnesoid X receptor; IL, interleukin; IRE1α, inositol-requiring enzyme-1α; JNK, c-Jun-N-terminal kinase; LPS, lipopolysaccharide; MAM, mitochondria-associated ER membrane; MAPK, mitogen-activated protein kinase; MTP, microsomal triglyceride transfer protein; NF-κB, nuclear factor-kappa-light-chain-enhancer of activated B cells; NLRP3, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasomes; PERK, protein kinase R-like ER kinase; ROS, reactive oxygen species; TGR5, Takeda G protein-coupled receptor 5; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor-α; UPR, unfolded protein response; VLDL, very-low density lipoprotein (created with BioRender.com, license purchased, accessed on 14 November 2023).
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Grants and funding

This research received funds from the Discovery Grant of the Natural Sciences and Engineering Research Council (NSERC) of Canada (RGPIN2016 05369) to H.P.V.R.