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Berberine ameliorates diabetic neuropathic pain in a rat model: involvement of oxidative stress, inflammation, and μ-opioid receptors

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Abstract

Berberine, a chemical found in plants, is used as a supplement for diabetes. This study aimed to investigate the effects and the underlying molecular regulations of berberine in diabetic neuropathic pain in a rat model of diabetes. Rats were injected with streptozotocin (STZ) to induce diabetes and then were treated with berberine. Blood glucose levels and body weight were measured. Thermal and mechanical nociception were assessed by paw pressure test and hot tail immersion test. Oxidative stress was assessed by lipid peroxidation, production of reactive oxygen species (ROS) and catalase activity. Neuroinflammation was assessed by tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) protein levels. Finally, μ-opioid receptor (MOR) protein and mRNA levels were measured. We found that berberine treatment partially suppressed blood glucose levels and restored body weight in diabetic rats. Berberine also suppressed STZ-induced oversensitivity of mechanical and thermal nociception. Additionally, berberine partially suppressed oxidative stress and inflammation of diabetic rats. Finally, berberine significantly enhanced protein and mRNA expression levels of μ-opioid receptor (MOR). Our findings suggest that berberine is a potential therapeutic alleviating diabetes and diabetic neuropathic pain, probably through suppression of oxidative stress and neuroinflammation that may be mediated by MOR.

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Author contribution statement

Jun Dong and Zhongfu Zuo contributed equally to this work. Jun Dong, Zhongfu Zuo, Wei Yan, and Wenqiang Liu conceived and designed research. Wenqiang Liu, and Qingyu Zheng analyzed data. Jun Dong and Xuezheng Liu wrote the manuscript. All authors read and approved the manuscript.

Funding

The study was supported by the National Natural Science Foundation of China (81571383); China Postdoctoral Science Foundation (2017 M612870); and Program for Liaoning Excellent Talents in University (LJQ2015069).

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Author notes

  1. Jun Dong and Zhongfu Zuo contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, Guangxi, China

    Jun Dong & Xuezheng Liu

  2. Department of Anatomy, Histology and Embryology, Jinzhou Medical University, No 3-40 Songpo Road, Jinzhou, 121001, Liaoning, China

    Jun Dong & Wei Yan

  3. Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Department of Anatomy, Histology and Embryology, Jinzhou Medical University, No 3-40 Songpo Road, Jinzhou, 121001, Liaoning, China

    Zhongfu Zuo, Wenqiang Liu, Qingyu Zheng & Xuezheng Liu

  4. Department of Anatomy, Histology and Embryology, Postdoctoral Research Station, Guangxi Medical University, Nanning, 530021, Guangxi, China

    Zhongfu Zuo

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  1. Jun Dong
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Correspondence to Xuezheng Liu.

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Dong, J., Zuo, Z., Yan, W. et al. Berberine ameliorates diabetic neuropathic pain in a rat model: involvement of oxidative stress, inflammation, and μ-opioid receptors. Naunyn-Schmiedeberg's Arch Pharmacol 392, 1141–1149 (2019). https://doi.org/10.1007/s00210-019-01659-6

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