Honokiol and hexafluoro-honokiol significantly increased neuronal networks and fiber density in enteric neurons and increased levels of neuronal nitric oxide synthase and Choline acetyltransferase mRNA. The effect of honokiol and hexafluoro-honokiol was assessed on neuronal phenotype, fiber density, differentiation, and pyroptosis. We used a previously established model of mouse primary enteric neuronal cells and an enteric neuronal cell line treated with palmitate (PA) and lipopolysaccharide (LPS) to induce mitochondrial dysfunction and enteric neuronal cell death. We studied the effects of honokiol and its fluorinated analog, hexafluoro-honokiol, on enteric neuronal differentiation and survival. Its role in modulating enteric neuron-specific neurodegeneration is unknown. Honokiol, a naturally occurring compound, is an activator of Sirtuin-3 (SIRT3) that has antioxidant activity. Enteric neuron degeneration has been observed during aging, and in individuals with metabolic dysfunction including obesity and diabetes.
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