High-fat diet-induced neuropathy of prediabetes and obesity: effect of PMI-5011, an ethanolic extract of Artemisia dracunculus L

Abstract

Artemisia species are a rich source of herbal remedies with antioxidant and anti-inflammatory properties. We evaluated PMI-5011, an ethanolic extract of Artemisia dracunculus L., on neuropathy in high-fat diet-fed mice, a model of prediabetes and obesity developing oxidative stress and proinflammatory changes in peripheral nervous system. C57Bl6/J mice fed high-fat diet for 16 weeks developed obesity, moderate nonfasting hyperglycemia, nerve conduction deficit, thermal and mechanical hypoalgesia, and tactile allodynia. They displayed 12/15-lipoxygenase overexpression, 12(S)-hydroxyeicosatetraenoic acid accumulation, and nitrosative stress in peripheral nerve and spinal cord. PMI-5011 (500 mg kg(-1) d(-1), 7 weeks) normalized glycemia, alleviated nerve conduction slowing and sensory neuropathy, and reduced 12/15-lipoxygenase upregulation and nitrated protein expression in peripheral nervous system. PMI-5011, a safe and nontoxic botanical extract, may find use in treatment of neuropathic changes at the earliest stage of disease.

Figure 1

Representative Western blot analyses ((a), (c), (e), (g)) and content (densitometry, ((b), (d), (f), (h))) of mouse sciatic nerve ((a)–(d)) and spinal cord ((e)–(h)) 12/15-lipoxygenase expressions after 16-week ((a), (b) and (e), (f)) and 23-week ((c), (d) and (g), (h)) feedings with normal chow or high-fat diet with or without PMI-5011. NC: normal chow, HF: high fat diet, T: treatment. Mean ± SEM, n = 7-8 per group. *^,**P < .05 and < .01 versus mice fed NC.

Figure 2

12(S)-hydroxyeicosatetraenoic acid concentrations in sciatic nerve ((a), (b)) and spinal cord ((c), (d)) after 16-week ((a) and (c)) and 23-week ((b) and (d)) feedings with normal chow or high-fat diet with or without PMI-5011. NC: normal chow, HF: high fat diet, T: treatment. Mean ± SEM, n = 9–13 per group. **P < .01 versus mice fed NC; ^§,§§ P < .05 and < .01 versus the baseline value (16-wk time point); ^£ P < .05 versus mice fed NC (16-wk time point); ^#,## P < .05 and < .01 versus untreated mice fed HFD (23-wk time point).

Figure 3

Representative Western blot analyses ((a), (c), (e), (g)) and content (densitometry, ((b), (d), (f), (h))) of mouse sciatic nerve ((a)–(d)) and spinal cord ((e)–(h)) nitrated protein expressions after 16-week ((a), (b) and (e), (f)) and 23-week ((c), (d) and (g), (h)) feedings with normal chow or high-fat diet with or without PMI-5011. NC: normal chow, HF: high fat diet, T: treatment. Mean±SEM, n = 7-8 per group. *^,**P < .05 and < .01 versus mice fed NC; ^§ P < .05 versus the baseline value (16-wk time point); ^#,## P < .05 and < .01 versus mice fed HFD.