Immunopharmacology and immunotoxicology · 2025
Beta-sitosterol alleviates inflammatory culprits and disease severity in arthritic irradiated rat's model: role of brain-spleen axis.
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El Bakary Nermeen M, Thabet Noura Magdy, Rashed Laila A, Azab Khaled Sh, Helal Hamed, Maarouf Rokaya E, Abdel-Rafei Mohamed K
Аннотация
BACKGROUND: The complex interaction between the adaptive immune system and innate immunological components causes rheumatoid arthritis (RA), a systemic autoimmune disorder that involves synovitis and joint deformity. Brain- spleen axis is a reciprocal cross-communicative circuit serves a crucial role in maintaining immunomodulation and homeostasis. RA complicates extra-articular manifestations in spleen and brain. Exposure to ionizing radiation might exacerbate the severity of RA. Recently, beta- sitosterol (BS), which is a promising phytosterols, has shown efficacy against various inflammatory models.
OBJECTIVE: Here, we aim at exploring the immunomodulatory effect of BS on the inflammatory responses in arthritic and arthritic-irradiated rats involving articular and extra-articular manifestation implicated in the brain-spleen axis.
MATERIALS AND METHODS: Adjuvant- induced arthritic rats were subjected to fractionated doses of γ-radiation (2 Gy/fraction once per week for 4 successive weeks, up to a total dose of 8 Gy) and either treated with BS (40 mg/kg b.wt./day, p.o.) or the standard anti-RA drug, methotrexate (MTX) (0.5 mg/kg; twice weekly, i.p).
RESULTS: BS ameliorated the arthritic clinical signs, improved histopathological insults, and osteopathological damage as revealed by X- radiography. Moreover, a notable alleviation in key inflammatory culprits was observed in ankle joints. Also, BS modulated apelin-13/APJ and protein kinase C (PKC)/AMP-activated protein kinase (AMPK)/nuclear factor erythroid-2-related factor-2 (Nrf2) signaling pathways in spleen and brain, as well as reduced oxidative stress, augmented antioxidant defenses, and diminished pro-inflammatory cytokines in serum, spleen, and brain that was supported histopathologically.
CONCLUSION: BS exhibited an immunomodulatory effect involving the brain-spleen axis in arthritic and arthritic-irradiated rats.
OBJECTIVE: Here, we aim at exploring the immunomodulatory effect of BS on the inflammatory responses in arthritic and arthritic-irradiated rats involving articular and extra-articular manifestation implicated in the brain-spleen axis.
MATERIALS AND METHODS: Adjuvant- induced arthritic rats were subjected to fractionated doses of γ-radiation (2 Gy/fraction once per week for 4 successive weeks, up to a total dose of 8 Gy) and either treated with BS (40 mg/kg b.wt./day, p.o.) or the standard anti-RA drug, methotrexate (MTX) (0.5 mg/kg; twice weekly, i.p).
RESULTS: BS ameliorated the arthritic clinical signs, improved histopathological insults, and osteopathological damage as revealed by X- radiography. Moreover, a notable alleviation in key inflammatory culprits was observed in ankle joints. Also, BS modulated apelin-13/APJ and protein kinase C (PKC)/AMP-activated protein kinase (AMPK)/nuclear factor erythroid-2-related factor-2 (Nrf2) signaling pathways in spleen and brain, as well as reduced oxidative stress, augmented antioxidant defenses, and diminished pro-inflammatory cytokines in serum, spleen, and brain that was supported histopathologically.
CONCLUSION: BS exhibited an immunomodulatory effect involving the brain-spleen axis in arthritic and arthritic-irradiated rats.