Table 1 MOA of polyphenols against aging-associated adipogenesis

Pro-Inflammatory Adipokines

Rutin

Cumaric acid

Ruta graveolens

Malus domestica

Enhanced the production of adiponectin while reducing the levels of leptin, PPARγ, and C/EBPα.

[32]

Resveratrol

Vitis vinifera

dose-dependently decreased leptin secretion, significantly reduced ATP levels in adipocytes

[33]

EGCG

Camellia sinensis

suppresses TNF-α, IL-1β, and IL-6 expression, increases SOD activity, decreases ROS expression

[36]

Epigenetic changes

Resveratrol

Vitis vinifera

Mitigates aging effects by enhancing H3K9ac and H3K27ac levels.

Modifies NRF2 pathway methylation to lower oxidative stress and fat accumulation.

[52]

Genistein,

EGCG

Glycine max

Camellia sinensis

potentially reverse DNA hypermethylation and restore silenced genes

[57, 160, 162]

TGF-β Signaling Pathway

EGCG

Camellia sinensis

inhibited the activity of the TGF/SMAD pathway,

restore autophagic activity in cells treated with TGF-β1, indicating that autophagic regulation is a key mechanism in EGCG’s action against TGF-β1-induced transformation. EGCG has the potential to slow down cellular aging, and the inflammatory processes induced by senescence

[62, 69, 163]

Ellagic acid

Punica granatum

Inhibits abnormal cell division and induce programmed cell death (apoptosis). Research suggests that EA may exert these effects by influencing the TGF-β/Smads signaling pathway, potentially leading to cell cycle arrest

[71]

Senescent cell accumulation

Resveratrol, quercetin,

curcumin, epigallocatechin-3-gallate (EGCG)

Vitis vinifera

Allium cepa

Curcuma longa

Camellia sinensis

Possess senolytic effects,

mitigate oxidative stress, reduce inflammation, and inhibit telomere shortening, while simultaneously enhancing DNA repair mechanisms and selectively eliminating senescent cells

[76, 161, 164]

Resveratrol

Vitis vinifera

induces cell senescence through the p53–p21 pathway, which is associated with both senescence and prolonged cessation of the cell cycle, alongside the p16/Rb pathway

[79]

Procyanidin C1,

Resveratrol,

Curcumin

Cinnamomum verum

Vitis vinifera

Curcuma longa

possess anti-aging properties by modulating p53/p21cip1

[81]

Quercetin

Allium cepa

Inhibit cellular proinflammatory pathways such as (ERK1/2)/P13K/AKT, (JNK)/P38 and MAPK

[71, 86]

AMPK Signaling

Genistein

Glycine max

Activates AMPK, leading to reduced expression of C/EBPα, apoptosis in mature adipocytes, inhibition of P38 MAPK phosphorylation, and prevention of adipocyte development.

[165]

Protocatechuic acid (PCA)

Prunus domestica

increases the expression of genes linked to longevity, including sir-2.1 and daf-16

[93, 166]

Resveratrol

Vitis vinifera

activates AMPK, thereby enhancing the effectiveness of the ROS defense mechanism.

Reduces mitochondrial dysfunction and oxidative stress through the LKB1/AMPK signaling pathway.

[96, 100]

Quercetin

Allium cepa

boosts UCP1 expression, suggesting heightened activity in BAT and browning of WAT

[98]

Oxidative stress

Quercetin

Allium cepa

Activates the Nrf2/NRF1 transcription pathway, enhancing the expression of antioxidant peroxiredoxins and providing protection against oxidative stress

[107]

Resveratrol

Vitis vinifera

prevented DNA fragmentation and apoptosis induced by 4-HNE

[167]

EGCG

Camellia sinensis

reduced the formation of free radical adducts, including 4-HNE adducts

[109]

PPAR-γ Transcription factor

Kaempferol

Pyrus malus

Proven effective in decreasing fat and lipid buildup linked to obesity. It works by boosting the levels of PPARα and PPARδ, along with their target genes, which helps to stimulate autophagy and improve fatty acid absorption.

[120]

Quercetin

Allium cepa

Boosts the conversion of WAT to brown fat and stimulates BAT by activating the β3-adrenergic receptor (β3AR) and the PKA/AMPK/PPARγ/PGC1α pathways. This activation results in higher levels of uncoupling protein 1 (UCP1) and ABCA1, which enhances ATP production and reduces fat accumulation.

[122]

Curcumin

Curcuma longa

stimulates PPARγ production, which in turn regulates insulin sensitivity and glucose homeostasis, while also reducing levels of inflammatory cytokines.

[124]

Hesperidin

Citrus sinensis

inhibits PPARγ, CCAAT-enhancer-binding protein β (C/EBPβ), SREBP1-C, and perilipin, demonstrating antiadipogenic and delipidating effects.

[125]

EGCG

Camellia sinensis

Inhibits the expression of genes associated with fat cell formation, such as PPARγ and C/EBPα, and blocks the development of preadipocytes into mature fat cells.

[126]

C/EBP Transcription factor

Genistein

Glycine max

inhibit FAS, SREBP 1, and aP2 in primary human adipocytes,

promoting mitochondrial biogenesis, inducing adipocyte beigeing, and upregulating UCP1 and cellular oxygen consumption

[130, 132]

cis-guggulsterone

Commiphora mukul

downregulates C/EBPβ, C/EBPα, and PPARγ2

[168]

EGCG

Camellia sinensis

Lower body weight and plasma lipid levels, while decreasing the expression of key genes involved in fat storage like PPARγ, C/EBPα, SREBP1, aP2, LPL, and FAS. At the same time, increase the expression of genes essential for breaking down fats, β-oxidation, and generating heat, which helps to prevent the formation of fat tissue.

[124]

Resveratrol

Vitis vinifera

Decreased lipid buildup and lowered the levels of LPL, FAS, C/EBPα, and SREBP-1c by activating AMPK

[124]

Sirtuins

Epicatechin

Camellia sinensis

reduces plasma triglyceride levels and increased expression of SIRT1, PGC-1α, and UCP1 in WAT

[135]

Resveratrol

Vitis vinifera

Directly interacts with the SIRT1 isoform, boosting its protective effects by regulating antioxidant responses.

[136, 137, 139, 141, 143]

Wnt Signaling Pathway

Flavonoids

Ginkgo biloba

Stimulate the Wnt pathway, which could prevent adipose stem cells from turning into fat cells.

[147]

Resveratrol

Vitis vinifera

stimulate Wnt/β-catenin signaling pathway

[147]

EGCG

Camellia sinensis

enhancing β-catenin levels while suppressing key genes involved in adipogenesis

[149]

Genistein

Glycine max

activate the Wnt pathway through ERK/JNK signaling and LEF/TCF4 coactivation, processes dependent on estrogen receptors.

[150]

Anti-inflammatory adipokines

EGCG

Camellia sinensis

provides anti-obesity benefits in humans by reducing ghrelin release and increasing adiponectin levels

[152]

Catechins

Camellia sinensis

significantly and dose-dependently increased adiponectin secretion

[153]

Chlorogenic acid

Coffea arabica

raise adiponectin levels in visceral adipose tissue and enhance the expression of AdipoR2 protein

[154]

Resveratrol

Vitis vinifera

Reduced the levels of vaspin gene expression in adipose tissue

[155]