Neuroprotective effects of xylopic acid on lipopolysaccharide-induced neuroinflammation

Oxidative stress and neuroinflammation are implicated in several central nervous system (CNS) disorders. Xylopic acid has CNS effects including anti-neuropathic pain [1], anxiolytic and antidepressant effects [2] while other kaurene diterpenes have protective effect against MPP⁺-induced neuronal death [3]. This study evaluates a possible neuroprotective effect of xylopic acid to help explain its myriad CNS effects. 8-week old mice received either xylopic acid (3, 10 or 30 mg/kg), fluoxetine (3, 10 or 30 mg/kg) or distilled water 10 ml/kg for 14 days. Neuroinflammation was then induced by intraperitoneal injection of 830 µg/kg lipopolysaccharide (LPS) [4]. 24h post LPS injection, sucrose preference test, forced swim and social interaction tests were performed to assess neurologic functions. Mice brain were remove 48h after LPS injection for antioxidant enzymes assay and staining for degenerating neurons. Brain derived neurotropic factor was also measured using ELISA. Xylopic acid attenuated LPS-induced depressive-like symptoms by reducing immobility, increasing sucrose preference and enhancing social interaction (F _{3, 35}= 56.14, P < 0.001). Oxidizing enzyme myeloperoxidase was significantly (F _{7, 32}= 7.251, P < 0.001) reduced while antioxidant enzymes superoxide dismutase and catalase activity were elevated along with increased glutathione levels. Lipid peroxidation was also ameliorated as indicated by reduced TBARS in xylopic acid-treated mice. Xylopic acid potently (EC₅₀= 1.72 ± 1.65, Emax = 93.92 ± 12.18) increased brain derived neurotropic factor as well as reduced neurodegeneration. These results indicate neuroprotective effects of xylopic acid which may contribute to its myriad beneficial CNS effects.

References:

[1] Ameyaw et al J Med Biomed Sci 2003; 2: :6 – 12

[2] Biney RP et al Planta Med 2014; 16

[3] Xu J et al Biosci Biotechnol Biochem 2011; 75: 1386 – 1388

[4] O'Connor JC et al Mol Psy 2009; 14: 511 – 522