Harpagophytum procumbens Inhibits Iron Overload-Induced Oxidative Stress through Activation of Nrf2 Signaling in a Rat Model of Lumbar Spinal Stenosis
Abstract
Lumbar spinal stenosis (LSS) is a common degenerative spinal condition in older individuals that causes impaired walking and other disabilities due to severe lower back and leg pain. Ligamentum flavum hypertrophy is a major LSS cause that may result from oxidative stress caused by degenerative cascades, including imbalanced iron homeostasis that leads to excessive reactive oxygen species production. We investigated the effects of Harpagophytum procumbens (HP) on iron‐induced oxidative stress associated with LSS pathophysiology. Primary spinal cord neuron cultures were incubated in FeSO4‐containing medium, followed by addition of 50, 100, or 200 μg/mL HP. Cell viability was assessed by CCK‐8 and live/dead cell assays and by propidium iodide‐live imaging. In an in vivo rat model of LSS, HP were administered at 100, 200, and 400 mg/kg, and disease progression was monitored for up to 3 weeks. We investigated the in vitro and in vivo effects of HP on iron‐induced neurotoxicity by immunochemistry, real‐time PCR, and flow cytometry. HP exerted neuroprotective effects and enhanced neurite outgrowths of iron‐injured rat primary spinal cord neurons in vitro. HP treatment significantly reduced necrotic cell death and improved cells’ antioxidative capacity via the NRF2 signaling pathway in iron‐treated neurons. At 1 week after HP administration in LSS rats, the inflammatory response and oxidative stress markers were substantially reduced through regulation of excess iron accumulation.…
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