Hemp seed oil mediates injury mitigation and anti-inflammation in radiated splenic T cells

Abstract

Background: Exposure to acute radiation results in hematopoietic damage, immune defects, and organ injury, ultimately leading to severe lethality. However, few drugs or compounds have been reported to effectively mitigate the injuries induced by high-dose ionizing radiation.

Methods: To elucidate the radioprotective mechanisms of hemp seed oil against acute radiation, lethal radiation was applied to evaluate the radio-protective function. The survival rates of mice were recorded, and the immune populations, particularly T cells, in the spleen were analyzed using flow cytometry. The expression of inflammation-related cytokines was detected for proving the anti-inflammatory function of hemp seed oil. Single-cell RNA sequencing was employed to explore the mechanisms underlying the radio-protective effects of hemp seed oil. In addition, we integrated HPLC-based phytochemical profiling with network pharmacology to identify bioactive constituents and characterize their molecular targets and signaling pathways.

Results: Hemp seed oil exhibited outstanding radio-protecting function, raising the survival ratio to above 50 % in mice exposed to lethal irradiation. Additionally, hemp seed oil preserved the immune populations, especially T cells, in the spleen. Single-cell RNA sequencing demonstrated that hemp seed oil alleviated oxidative stress, apoptosis, and inflammation-related features in T cells. Treatment with hemp seed oil enhanced the expression of inflammation-suppressing genes and promoted the differentiation of naïve CD4 T cells towards Treg cells. Further analyses indicated that the enhanced differentiation of Treg cells induced by hemp seed oil might be contributed by signals from fibroblasts through upregulated Itgb8. Meanwhile, HPLC analysis characterized 10 bioactive compounds in hemp seed oil. Integrating network pharmacology with in silico molecular docking revealed statistically significant correlations between these phytochemicals and key pathways regulating immune response and inflammatory processes, suggesting multitargeted immunomodulatory effects.

Conclusions: This research demonstrated a strong role of hemp seed oil in increasing survival rates and protecting splenic lymphocytes in mice facing acute irradiation. These findings offer a promising alternative for radioprotective medications and provide insights into the mechanisms underlying the radio-protective effects of hemp seed oil.

Keywords: Hemp seed oil; Inflammation; Network pharmacology; Radiation injury; T cell.