## 4 Discussion  
In recent years, dietary phytochemicals and botanicals received the scientific community's attention regarding their potential use as a complementary and alternative therapy to either prevent, manage, or treat several diseases, including stress and depressive symptoms, with minimum side effects, in comparison to allopathic treatments, known to exert several adverse effects such as gastrointestinal problems, sleep disturbances, sexual dysfunction, congenital disabilities, seizures, and even death, among others [8]. Dietary phytochemicals are a part of our daily diet, easy to find, and cheap. Additionally, they have a safe \"green image\" that may potentially help to prevent and alleviate MDD symptoms. In this respect, many studies and experiments demonstrated that several polyphenols might produce an antidepressant-like effect [26]. The Chinese Health Ministry has recorded safflower formulations as a drug against cardiovascular diseases [27]. Safflower is one of the plants that has been used in traditional and modern medicine for years in several countries. Many studies illustrated the protective effect and other health benefits on musculoskeletal and cardiovascular systems and reproductive organs [12]. Safflower is known for its bioactivities such as anti-inflammatory, antioxidant, and antitumor effects [28]. Precisely, the water extract of safflower is considered an anticoagulant, vasodilating, antihypertensive, antioxidative, neuroprotective, immunosuppressive, and anticancer agent [12]. Our study demonstrated that safflower dried petals hot water extract exerts an antidepressant effect in mice subjected to TST and FST-induced stress, as shown by the improvement in the percentage of spontaneous alternation in YMSAT. The tail suspension test is an inexpensive and easy-to-use behavioral test used to detect depression-related behaviors and measure the potentiality of antidepressants on mice since the 1980s. TST has advantages over other behavioral tests in overcoming motor dysfunction of the mice and hypothermia issues [29]. A forced swimming test is also another widely used, easy, inexpensive, and fast behavioral test that could be used along with TST. TST and FST both use immobility as a measurement that represents depressive behavior. FST contributes to depression research, especially in genetic analysis, where immobility in FST is determined by heritable traits [30]. The Y maze test could easily assess the memory and learning patterns of mice, which allows continuous spontaneous alternation. During this test, the hippocampus is hugely involved in retrieving essential information for building a mental map [31]. Fluoxetine (C17H18F3 NO) is a high CNS penetration, orally administrated, and widely used drug, which is a selective serotonin reuptake inhibitor (SSRI) antidepressant [32]. Chromotagraphic analysis showed that oleamide (9-octadecemamide) would be the main active ingredient extracted in high yield in water than in hydro-alcoholic solvent. Moreover, we report for the first time the optimum procedure of extraction that yielded 46% oleamide-rich tea by soaking safflower in water at 115 \({}^{\circ}\)C for 1 min. Olamide is known as a hypnotic and sedative chemical entity that naturally accumulates in human and mammals cerebrospinal fluid during sleeping deprivation as a natural modulator to induce sleeping and/or to reduce psychological excitement through the interaction with the cannabinoid receptor [33]. Additionally, oleamide was reported to interact with several neurotransmitter-receptor systems, including serotonin and GABA [34]. Moreover, oleamide provides anti-inflammatory activity along with other pharmacological properties such as human monoamine oxidase B enzyme inhibitor and TRPV1 vanilloid receptors activator [35]. Our study reports for the first-time safflower extract-administered mice 'hippocampus transcriptomic profiling. Transcriptome analysis, including highly reproducible and significant target genes (\(p<0.001\)), resulted in a pool of 22 genes.