Abstract: BACKGROUND: Immunosuppressants such as cyclophosphamide impair immune function, leading to cognitive impairment. Herbal cake-separated moxibustion and moxa-stick moxibustion effectively modulate immune function and improve cognitive dysfunction; however, their mechanisms of action remain incompletely understood.
OBJECTIVE: To investigate potential mechanisms by which different moxibustion methods influence cognitive impairment in immunosuppressed rats.
METHODS: Forty SD rats were randomly divided into a blank control group, a model group, a cake-separated moxibustion group, and a moxa-stick moxibustion group, with 10 rats in each group. Cyclophosphamide (30 mg/kg) was intraperitoneally injected for 3 consecutive days to induce immunosuppression rat models, in the latter three groups. Following modeling, rats in the cake-separated moxibustion group and moxa-stick moxibustion groups received corresponding interventions for 10 consecutive days. After intervention, cognitive function was assessed using the open field test. Serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α, as well as brain tissue levels of interleukin-18, were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining and immunohistochemistry were used to observe morphological changes and detect nuclear factor κB expression in brain tissue, respectively.
RESULTS AND CONCLUSION: (1) Compared with the blank control group, the number of rearings, total travel distance, distance traveled in the central zone, and time spent in the central zone in the open field test were decreased (P < 0.01); serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly decreased (P < 0.01, P < 0.001, P < 0.001, respectively); nuclear factor κB expression and IL-18 levels in brain tissue were significantly increased (P < 0.001); and hippocampal neurons exhibited disorganized alignment, with some nuclei showing deep staining due to nuclear condensation and lymphocytic infiltration in the model group. (2) Compared with the model group, the number of rearings, total travel distance, distance traveled in the central zone, and time spent in the central zone in the open field test were significantly increased (P < 0.05); serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were significantly elevated (P < 0.05, P < 0.01, P < 0.01), while nuclear factor κB expression was significantly reduced (P < 0.05); brain tissue IL-18 levels in brain tissue were significantly decreased (P < 0.01); and hippocampal neuronal alignment was more orderly, lymphocytic infiltration was reduced, and nuclear condensation and vacuolation were markedly less pronounced in the cake-separated moxibustion group. (3) Compared with the model group, total travel distance and time spent in the central zone in the open field test were significantly increased (P < 0.05), with no significant difference in the number of rearings and distance traveled in the central zone; and serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α significantly increased (P < 0.05), while no significant difference in nuclear factor κB and interleukin-18 levels were found in brain tissues in the moxa-stick moxibustion group. (4) Compared with the moxa-stick moxibustion group, interleukin-18 levels in brain tissue significantly reduced (P < 0.05), with no significant differences in other indicators in the cake-separated moxibustion group. These results suggest that herb cake-separated moxibustion may alleviate neuroinflammation by inhibiting nuclear factor-κB signaling pathway activation, thereby improving cognitive function in immunosuppressed rats. The cake-separated moxibustion shows superior therapeutic efficacy for immunosuppression to moxa-stick moxibustion.

Key words: immunosuppression, cake-separated moxibustion, moxa-stick moxibustion, nuclear factor κB pathway, neuroinflammation, cognitive function, cyclophosphamide, interleukin, tumor necrosis factor