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.
