## 4 Discussion
While compounds with CA ratios > 1 are more likely to exert biological effects at attainable plasma levels, considering previous studies indicating that lycopene exerts biological activity at nanomolar concentrations [53, 54, 55], particularly within membrane-rich environments or lipid rafts where its accumulation is higher [56, 57], it is likely that other lycopene targets with CA ratios < 1 can potentially be involved in its pharmacodynamic effects. Protein-protein interaction network analysis further identified a subset of targets with significant biological relevance. We identified 32 high-interaction and 9 significant-interaction proteins, with some of these targets (_TRIM24_, _GRIN1_, _NTRK1_, _FGFR1_, and _NTRK3_) exhibiting binding affinities below 10 uM. Although their CA ratios remained low (<0.03), these targets may act as secondary effectors or are relevant in tissues with higher lycopene accumulation, such as the prostate, liver, and adrenal glands [16, 52]. _TRIM24_, _GRIN1_, _NTRK1_, _ FGFR1_, _NTRK3_, _CHRNB4_, and _PIK3 CD_ are key proteins with diverse biological roles, many of which are relevant to disease pathogenesis and potential pharmacological targeting [58, 59, 60]. _TRIM24_ is a transcriptional co-regulator that modulates nuclear receptor signalling and chromatin remodelling. It plays a critical role in cell proliferation and apoptosis and has been implicated in the development of several cancers, particularly breast and liver malignancies [61, 62]. GRIN1 encodes a core subunit of NMDA receptors essential for calcium ion influx during synaptic transmission. It is central to learning, memory, and neural development, and its dysregulation is associated with neurodegenerative diseases consequence to excitotoxicity [63, 64]. Alterations in _NTRK1_ is linked to various cancers and sensory disorders, while _NTRK3_ is associated with breast carcinoma and congenital fibrosarcoma [65, 66]. _FGFR1_, by mediating pathways involved in growth, angiogenesis, and tissue repair, contributes to developmental syndromes and several cancers, while _CHRNB4_ is critical for synaptic transmission in the nervous system and is implicated in neurological conditions such as epilepsy, schizophrenia, and nicotine dependence [67, 68, 69]. _PIK3 CD_ is predominantly expressed in immune cells and regulates pathways central to immune function, and its mutations are associated with primary immunodeficiencies like Activated PI3K-Delta Syndrome [70]. Hence, _PIK3 CD_ is a target of interest in autoimmunity and cancer therapy. These novel observations in our study on the diverse pathophysiological role of lycopene targets identified are consistent with several clinical investigations and reports on the potential use of lycopene for healthcare [21; 71; 72]. Expression profiling of the highest-affinity targets provided further insight into the tissue-specific pharmacodynamics of lycopene. Except for _SLC6A5_, whose protein expression data is unavailable, the remaining high-affinity targets showed expression in a range of tissues. _MAP2K2_, _SCN3A_, _TOP2A_, and _TRIM24_ are functionally involved in oncogenic signalling, neuronal excitability, and DNA repair, offering diverse but interconnected avenues for pharmacological intervention. Particularly, _MAP2K2_, _SCN3A_, _TOP2A_, and _TRIM24_ were co-expressed in reproductive and endocrine tissues (seminal vesicle, adrenal gland, and cervix). These results are consistent with past transcriptomic studies that observed the upregulation of lycopene-responsive genes in prostate and mammary tissues [57; 73; 74]. Consistent with our observation, a recent study also demonstrated _MAPK_ pathway to be a target of lycopene in alleviating renal ischemia-reperfusion injury in an animal model [34]. _MAP2K2_ is a critical component of the _MAPK/ERK_ signalling pathway, which regulates cell proliferation, differentiation, and survival.