Phoenix dactylifera L. (date palm) is an essential agricultural crop in most arid regions
of the world and have been used in traditional medicine to treat illnesses. The extracts of P.
dactylifera pulps and seeds are reported to possess valuable pharmacological attributes including
antioxidant, anti-fungal and anti-inflammatory activity. However, there is still a lack of
scientific data to support the potency of P. dactylifera in treating inflammation. Thus, the
primary purpose of this study is to fill in the current research gap concerning the mechanism
underlying the anti-inflammatory effects of this fruit crops. There are many date varieties
available in the market with various phenotypic features, consumers’ preferences and price ranges.
Eighteen varieties of dates from two date producing countries were selected including
Algerian Lahmira (LM), Timjouhert (TM), Adham Talmine (AT), Deglet Talmine (DT), Adam Boullah
(AB), Tinasser (TN), Deglet (DG), Deglet Nour (DN) and Takerbouch (TB) along with Saudi
varieties of Berni (BR), Halaoua (HL), Shalabi (SB), Sogaai (SG), Sukkari (SK), Nebtat
Ali (NB), Anbara (AN), Ajwa (AJ) and Medjoul (MJ). The quality was evaluated based on the
metabolite composition, physico-chemical characteristics and biological activities which include
nitric oxide (NO) inhibition via the cell-based approach and NO scavenging abilities. The
correlation between the phytochemicals and biological activities was achieved via ¹H nuclear
magnetic resonance (NMR) based metabolomics approach. Algerian Deglet and Saudi Ajwa
showed the most promising NO inhibition as compared to the rest of date varieties. The current
study was then focusing on the variation in phytochemicals and biological activities between the
seeds and pulps of P. dactylifera. The information on chemical constituents was further strengthen
utilizing ultra-high performance liquid chromatography mass spectrometry (UHPLC-MS)
technique. The multi-platforms metabolomics of MS and NMR methods were adopted in exploring
differences between the phytochemical in seed and pulp extracts. The seed of Algerian Deglet
revealed a significantly lower IC50 values of NO inhibitory and DPPH scavenging with the IC50
values of 107.99 µg/mL and 12.58 µg/mL, respectively. Among the metabolites that prominently contributed
towards the observed bioactivities as suggested by Partial Least Squares analysis
including catechin, ascorbic acid and serine. The proposed metabolic pathway indicated the
higher amount of several metabolites in date seeds as compared to the pulps. The variation between
the extracellular metabolites of RAW 264.7 cells from different passage numbers was determined
along with the impact of different harvesting protocols on the intracellular metabolites. The
trypsinized RAW cells from lower passage groups gave higher intensities of several
metabolites including asparagine, serine and tryptophan. The Principal Component Analysis
revealed variation between cells from different passage and harvesting methods as indicated by the
formation of clusters in the score plot. The current study is the first to report on the passage
and harvesting dependent effects using metabolomics workflow for the murine macrophage, RAW
264.7 cells. The overall bio-markers from the cell metabolome of the induced and treated
cells and also bio-active compounds in date extracts linking to the anti-inflammatory property was
obtained in the present study. The acquired data adds up to the existing knowledge on
anti-inflammatory effects of date seed extracts by highlighting their capacity to assist the
inversion of activated RAW 264.7 cells back to the normal state. This work demonstrated
the potential application of metabolomics approaches as tools in evaluating quality of
plant
materials and also in providing better insight into cells biology
