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. 2022 Feb 25;11(3):462.
doi: 10.3390/antiox11030462.

Potential Valorization of Edible Nuts By-Products: Exploring the Immune-Modulatory and Antioxidants Effects of Selected Nut Shells Extracts in Relation to Their Metabolic Profiles

Mohamed A Salem  1 , Nora M Aborehab  2 , Ahmed A Al-Karmalawy  3 , Alisdair R Fernie  4   5 , Saleh Alseekh  4   5 , Shahira M Ezzat  6   7
Affiliations

Potential Valorization of Edible Nuts By-Products: Exploring the Immune-Modulatory and Antioxidants Effects of Selected Nut Shells Extracts in Relation to Their Metabolic Profiles

Mohamed A Salem et al. Antioxidants (Basel). .

Abstract

The immune system is a potent army that defends our body against various infections and diseases through innate and adaptive immunity. Herbal medicine is one of the essential sources for enhancing immunity because of affordability, availability, minor side effects, and consumers' preferences. Hazelnuts, walnuts, almonds, and peanuts are among the most widespread edible nuts that are rich in phenolics, fats, fibers, vitamins, proteins, and minerals. The potential of nut shells in phytoremediation has attracted increasing attention as a sustainable solution for waste recycling. Here, we determined the in vitro immune-modulatory activity as well as the metabolite profile of the four nut shell extracts. The addition of the extracts to LPS-stimulated macrophages, especially peanut and walnut shells, has downregulated the gene expression of AP-1, TNF-α, IL-8, iNOS, and COX-2 expression levels. Significant antioxidant capabilities and immune-modulatory effects have been traced for peanut shells. UPLC-MS metabolic profiling of the four nut shell extracts allowed the detection of a relatively high level of phenolic compounds in peanut shells. Intriguingly, a significant correlation between the antioxidant capacity and the total phenolic content was found, indicating the contribution of the phenolic compounds to the antioxidant properties and hence the immune-modulatory activity. Furthermore, molecular docking and structure-activity relationship (SAR) studies revealed kaempferol rutinoside and proanthocyanidin A5' as potential iNOS inhibitors.

Keywords: SAR; by-products; immune-modulatory; metabolomics; molecular docking; nuts; shells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Evaluation of the total phenolics contents and antioxidant potential of nut shell extracts.
Figure 2
Figure 2
The biochemical effect of different nut shell extracts on NF-KB, Cox-2, iNOS and SP-1 expression levels. # Significant from Positive control at p < 0.0001, @ Significant from Peanut shells at p < 0.0001.
Figure 3
Figure 3
The biochemical effect of different nut shell extracts on AP-1 expression level. # Significant from Positive control at p < 0.0001, @ Significant from Peanut shells at p < 0.0001.
Figure 4
Figure 4
Total ion chromatogram (TIC) and extracted ion chromatograms (EIC) of the peak at 575.12024 m/z representing proanthocyanidin A2 measured by UPLC/MS in negative ionization mode with schematic diagram showing the production of fragment ions during MS/MS analysis.
Figure 5
Figure 5
Principal component analysis (PCA) scores plot (A) and hierarchical cluster analysis (HCA) (B) of nut shell extracts based on the UPLC/MS data.
Figure 6
Figure 6
Metabolites with significant accumulation in peanut shell extract. The y-axis represents the scaled and log10-transformed values of metabolite abundance.
Figure 7
Figure 7
Structure–Activity relationship (SAR) study of the selected compounds of the studied four nut shell extracts as potential iNOS inhibitors.
Figure 8
Figure 8
Suggested molecular mechanism of peanut shells bioactive metabolites as immunomodulatory.
See this image and copyright information in PMC

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