## 4 Discussion
Interestingly, some of the genes are highly relevant to MDD, anxiety, and neurobehavior. A study on rats has revealed that NcoR (nuclear receptor corepressor) expression reduction within the developing amygdala is associated with a significant increase in anxiety-like behavior during the juvenile period in both genders [36]. On the contrary, hippocampal NcoR1 was upregulated in the control group with an average of 1.33 log2 for the three replicates, while a significant reduction in expression level was detected in SFPWH (50 mg/kg) group with \(-1.4\) log2 fold. However,no significant difference was detected in SFPWH (150 mg/kg) and fluoxetine (10 mg/kg) groups. The gene ontology enrichment analysis showed that NeoR1 involves in the thyroid hormone signaling pathway (33.15-fold enrichment, FDR 0.0030). Noting that an adequate level of thyroid hormone is essential for the brain to function normally [37]. Apoptosis plays an important role in the development of the brain and the peripheral nervous system as well [38]. There is a link between apoptosis and major depressive disorder and other neurodegenerative diseases such as Parkinson's and Alzheimer's disease [38]. Casp9 is one of the differentially expressed genes in the SFPWH (50 mg/kg)-treated group and the enrichment analysis revealed involvement in several pathways, including apoptosis and neurodegeneration. Interestingly, casp9 was highly expressed in SFPWH (50 mg/kg) group (2.67 log2 fold) in comparison with the control group (\(-\)1.27 log2 fold). Glutamate is a neurotransmitter that has an excitatory effect [39]. Glutamate system abnormalities and behavior that lead to several disorders, including MDD, were linked [39]. In our study, Grik1 (glutamate receptor, ionotropic, kainate 1) was significantly downregulated (\(-\)1.29 log2 fold) in SFPWH (50 mg/kg) group. It has been reported that female patients with MDD showed a significantly higher expression level of the Grik1 gene in the dorsolateral prefrontal cortex [39]. Ube2j2 gene is predicted to be involved in protein polyubiquitination and ubiquitin-dependent endoplasmic reticulum-associated protein degradation pathway [40]. Endoplasmic reticulum stress has a major role in the pathophysiology of depression, where an abnormal function is linked with triggering apoptosis signals [41]. In our study, Ube2j2 was significantly downregulated in SFPWH (50 mg/kg) group (\(-\)2.06 log2 fold) compared to the control group. Transcriptomic analysis revealed two transcripts of the Dctn6 gene that were expressed differently. However, Dctn6-202 is the transcript that encodes the protein Dynactin subunit 6. The function of Dctn6 involves enabling dynein complex binding activity [42]. It has been reported that chronic stress reduces the dynein motor protein expression in the rat hippocampus [43]. In SFPWH (50 mg/kg) group, the Dctn6-206 transcript was downregulated (\(-\)1.90 log2 fold) while the transcript Dctn6-202 was upregulated (1.84 log2 fold). Tuba1c is another significantly downregulated gene detected in SFPWH (50 mg/kg) group. It is predicted that Tuba1c, which encodes Tubulin alpha-1C chain protein, enables GTP binding activity and structural constituent of the cytoskeleton [44]. Cytoskeletal (microtubules) post-translation modification is linked with several neuropsychiatric diseases [45]. In our study, the data analysis showed that Tuba1c is involved with several pathways, including neurodegeneration, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and apoptosis pathways. Cacna1h gene was significantly downregulated in the fluoxetine-treated group with an average of \(-\)1.42 log2 fold. It has been reported that mice deficient in CaV3.2 channels, which is encoded by the Cacna1h gene, showed an increase in anxiety-like behavior [46], where safflower hot water extract-treated and control groups were not significantly different.