## 4 Discussion
In the current study, the GMP treatment decreased the levels of IFN-\(\gamma\) in AD mice and reduced the production of IL-17 in PI-stimulated EL4 cells, suggesting that GMP can also modulate the activities of Th1/Th17 cells to improve the AD symptoms. ADHD is one of the most prevalent neuropsychiatric comorbidities in AD patients. The severity of AD may result in emotional and behavioral problems, contributing to an increased incidence of ADHD [41; 42]. In this study, AD mice exhibited ADHD-like symptoms, as inferred from the increased total distance travel and speed in the OFT. The hyperactivity in AD mice was also indicated by a moderate increase in the distance in open arms of the EPM. In contrast, treatment with GMP could attenuate the hyperlocomotion behavior in AD mice, indicating the beneficial effects of GMP on psychiatric comorbidities of AD. Neuroinflammation plays an important role in the development of ADHD [43]. Several immune cells, such as microglia, astrocytes, and mast cells are involved in the development of neuroinflammation by secreting inflammatory cytokines, such as TNF-\(\alpha\), IL-6, and IL-18 [44; 45]. In the present study, the level of TNF-\(\alpha\) in PFC was increased in the AD mice, and the TNF-\(\alpha\) level positively correlated with hyperactivity behavior. This was reduced by the GMP treatment, suggesting that GMP improved behavioral changes in AD mice by inhibiting neuroinflammation. Typical steroids are commonly used to treat AD because they can reduce inflammation and itching symptoms in dermatitis [46]. On the other hand, long-term skin treatment of these steroids might result in various adverse effects such as skin atrophy, impaired skin barrier function, and drug resistance [47]. The results showed that some biomarkers were improved by the DEX treatment, but the overall clinical severity was worsened in the DEX group compared to the GMP group. The GMP group did not have any side effects, even after long-term treatment, highlighting the safety of GMP for AD treatment. HPLC showed that quassin is a major component of GMP. A previous study indicated the anti-inflammatory activity of quassin by suppressing the expression of inflammatory molecules, including iNOS2, TNF-\(\alpha\), IL-10, and IL-12 in murine macrophages [48]. In addition, quassin exerted neuroprotective effects by increasing the viability of SH-SYSY neuroblastoma cells under H\({}_{2}\)O\({}_{2}\) stimulation [49]. These findings suggest that quassin might improve the therapeutic effects of GMP against DNCB-induced skin inflammation and behavioral changes in mice. This study still had some limitations that can be improved in future studies. Several other behavioral tests for evaluation of other psychiatric symptoms in AD mice, such as depression (sucrose preference test, tail suspension test) should be conducted for a more detailed conclusion about AD-associated psychiatric disorders in the mouse model. The effects of GMP on signaling pathways related to AD can also be examined to investigate the underlying mechanisms. Therefore, further studies should be performed to provide more scientific evidence for the efficacy of GMP for AD treatment.