Apigenin Mitigates Intervertebral Disc Degeneration through the Amelioration of Tumor Necrosis Factor α (TNF-α) Signaling Pathway

Abstract

BackgroundIntervertebral disc degeneration (IDD) is a common spinal disease affected by environmental and lifestyle factors that has a significant pathological cascade toward inflammation and partial disability. There is currently no therapy that can completely restore the cellular derangement in IDD. Hence, in this study, the therapeutic effects of apigenin on IDD were evaluated using a rat model.Material/MethodsAnimals were separated into 4 groups: Grp 1, sham-operated control; Grp 2, IDD-induced; Grp 3, IDD-induced+apigenin treatment; Grp 4, apigenin control. The animals were assessed for inflammatory cytokines, chemokines, and prostaglandin signaling.ResultsThere were significant increases in the inflammatory cytokines IL-1β, IL-2, IL-6, IL-8 and IL-17 in the IDD-induced group compared to that of control. Moreover, with increased levels of MMP-3, MMP-9, ADAMTS-4, and syndecan-4, the levels of TNF-α, IFN-γ, prostaglandin E2, and cyclooxygenase 2 were directly increased in the IDD-induced group. In contrast, apigenin protectively restored levels of prostaglandin signaling and reduced cytokine levels. In addition, nucleus pulposus cells cultured separately with either TNF-α inhibitor or apigenin significantly attenuated the levels of extracellular matrix proteins.ConclusionsThe reduction of cytokine levels under apigenin treatment suggests it may be a promising target drug therapy for the treatment of deleterious IDD conditions.