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Review
. 2024 Aug 10;13(8):974.
doi: 10.3390/antiox13080974.

Mechanistic Insights into the Biological Effects and Antioxidant Activity of Walnut (Juglans regia L.) Ellagitannins: A Systematic Review

Letiția Mateș  1 , Roxana Banc  2 , Flaviu Andrei Zaharie  3 , Marius Emil Rusu  4 , Daniela-Saveta Popa  1
Affiliations
Review

Mechanistic Insights into the Biological Effects and Antioxidant Activity of Walnut (Juglans regia L.) Ellagitannins: A Systematic Review

Letiția Mateș et al. Antioxidants (Basel). .

Abstract

Walnuts (Juglans regia L.) are an important source of ellagitannins. They have been linked to positive effects on many pathologies, including cardiovascular disorders, neurodegenerative syndromes, and cancer. The limited bioavailability of ellagitannins prevents them from reaching significant circulatory levels, despite their antioxidant, anti-inflammatory, and chemopreventive properties. Urolithins are ellagitannin gut microbiota-derived metabolites. They have better intestinal absorption and may be responsible for the biological activities of ellagitannins. Recent evidence showed that walnut ellagitannins and their metabolites, urolithins, could have positive outcomes for human health. This study aims to synthesize the current literature on the antioxidant activity and mechanistic pathways involved in the therapeutic potential of walnut ellagitannins and their metabolites. In the eligible selected studies (n = 31), glansreginin A, pedunculagin, and casuarictin were the most prevalent ellagitannins in walnuts. A total of 15 urolithins, their glucuronides, and sulfate metabolites have been identified in urine, blood, feces, breast milk, and prostate tissue in analyzed samples. Urolithins A and B were associated with antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anticarcinogenic, and anti-aging activities, both in preclinical and clinical studies. Despite the promising results, further well-designed studies are necessary to fully elucidate the mechanisms and confirm the therapeutic potential of these compounds in human health.

Keywords: anti-cancer; anti-inflammatory; biological activity; cardiometabolic health; clinical studies; ellagic acid; in vitro; in vivo; oxidative stress; urolithins.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram of study selection.
Figure 2
Figure 2
The main metabolites of ETs and EA formed after walnut (J. regia L.) intake by intestinal microbiota (created with BioRender.com).
Figure 3
Figure 3
The mechanisms of ellagitannins, ellagic acid, and urolithins and their multiple beneficial health effects after walnut consumption (AGEs—advanced glycation end products; BDNF—brain-derived neurotrophic factor; CA2—carbonic anhydrase 2; CAT—catalase; CRC—colorectal cancer; CPS1—carbamoylphosphate synthetase; CREB—cAMP-response element binding protein; CSCs—cancer stem cells; EA—ellagic acid; ETs—ellagitannins; HOC—hippocampal occupancy score; HOMA-IR—Homeostatic Model Assessment for Insulin Resistance; ICAM-1—intracellular adhesion molecule 1; IL—interleukin; INF-γ—interferon gamma; LDL-c—low-density lipoprotein cholesterol; MDA—malondialdehyde; NAFLD—non-alcoholic fatty liver disease; NF-κB—nuclear factor kappa-light-chain-enhancer of activated B cells; NASH—non-alcoholic steatohepatitis; ORAC—oxygen radical absorbance capacity; PCa—prostate cancer; PKA—protein kinase A; ROS—reactive oxygen species; SCFA—short-chain fatty acids; SOD—superoxide dismutase; TG—triglycerides; TNFα—tumor necrosis factor-α; T-AOC—total antioxidant capacity; UM—urolithin metabotypes; Uros—urolithins; VCAM-1—vascular cell adhesion molecule 1; WAT—white adipose tissue; ↑—increases; ↓—decreases).
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