The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain

Evidence-Based Complementary and Alternative Medicine, Nov 2015

Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 μg BE could inhibit the production of IL-6 and TNF-α in the spinal cord of CIBP rats. Moreover, intrathecal 100 μg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-α and through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP.

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The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain

The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain Shan Hu,1 Yu Chen,2 Zhi-Fu Wang,3 Qi-Liang Mao-Ying,1 Wen-Li Mi,1 Jian-Wei Jiang,1 Gen-Cheng Wu,1 and Yan-Qing Wang1 1Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Shanghai Medical College, Institutes of Brain Science, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China 2Guiyang Medical University, 9 Beijing Road, Guiyang, Guizhou 550004, China 3Department of Anatomy, Integrative Medicine College, Fujian University of Traditional Chinese Medicine, Qiu Yang Road, Minhou, Fuzhou, Fujian 350122, China Received 3 June 2015; Revised 20 September 2015; Accepted 21 September 2015 Academic Editor: Ke Ren Copyright © 2015 Shan Hu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Cancer-induced bone pain (CIBP) is a severe type of chronic pain. It is imperative to explore safe and effective analgesic drugs for CIBP treatment. Baicalein (BE), isolated from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi (or Huang Qin), has been demonstrated to have anti-inflammatory and neuroprotective effects. In this study, we examined the effect of BE on CIBP and the mechanism of this effect. Intrathecal and oral administration of BE at different doses could alleviate the mechanical allodynia in CIBP rats. Intrathecal 100 μg BE could inhibit the production of IL-6 and TNF-α in the spinal cord of CIBP rats. Moreover, intrathecal 100 μg BE could effectively inhibit the activation of p-p38 and p-JNK MAPK signals in CIBP rats. The analgesic effect of BE may be associated with the inhibition of the expression of the inflammatory cytokines IL-6 and TNF-α and through the activation of p-p38 and p-JNK MAPK signals in the spinal cord. These findings suggest that BE is a promising novel analgesic agent for CIBP. 1. Introduction Cancer-induced bone pain (CIBP) results from multiple primary diseases, such as breast, lung, and prostate cancer, and severely impairs the quality of life of patients [1–3]. However, because of the complicated mechanism of CIBP and the lack of a proper animal model for studying CIBP, it remains a serious medical problem [4]. In the past two decades, several animal models have been established to help examine the mechanism of CIBP [5–7]. To date, results from our lab and others have demonstrated that CIBP is a complex pain state involving components of both neuropathic and inflammatory pain [5, 8, 9]. We observed significant levels of activated astrocytes and microglia cells and a subsequent robust increase in the expression of proinflammatory cytokines in the spinal cord of CIBP rats [10–12]. These cellular and molecular changes in the spinal cord are characteristic of neuroinflammation, which is critical for the development of CIBP. Baicalein (BE) is a bioactive flavonoid derived from the root of Scutellaria baicalensis Georgi (or Huang Qin), which is widely used in Chinese herbal medicine [13, 14]. Evidence has shown that BE has many pharmacological effects, including antiallergic, antioxidant, antiapoptotic, antiviral, anti-inflammatory, antitumor, and neuroprotective effects and a modulatory effect on the immune system [15–19]. BE is also known as a nonselective 12/15-lipoxygenase (12/15-LOX) inhibitor that suppresses inflammation and proliferation and induces apoptosis in various cancers [20–22]. Whether BE can attenuate the neuroinflammation in the spinal cord that is characteristic of CIBP needs to be explored. Therefore, the present study characterized the effect of BE on spinal neuroinflammation in CIBP rats. We hypothesized that the analgesic effect of BE is primarily due to the inhibition of the expression of proinflammatory mediators and the excessive activation of related signaling pathways. 2. Materials and Methods2.1. Animals Female Sprague-Dawley (SD) rats weighing 160–180 g were purchased from Shanghai Laboratory Animal Center, Chinese Academy Sciences. All animals were maintained in a climate-controlled room on a 12 h light-12 h dark cycle and were given unrestricted access to food and water. They were acclimatized to this for at least a week before the initiation of the experiments. All experimental procedures were approved by the Animal Care and Use Committee (ACUC) of Fudan University and were consistent with the NIH’s Guide for the Care and Use of Laboratory Animals and the Ethical Issues of the IASP. 2.2. Surgical Procedures Walker 256 rat mammary gland carcinoma cells were prepared as previously described [7, 23]. After the animals were anesthetized with sodium pentobarbital (i.p. 50 mg/kg), suspensions of 4 × 105 tumor cells in 4 μL 0.01 MPBS follo (...truncated)


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Shan Hu, Yu Chen, Zhi-Fu Wang, Qi-Liang Mao-Ying, Wen-Li Mi, Jian-Wei Jiang, Gen-Cheng Wu, Yan-Qing Wang. The Analgesic and Antineuroinflammatory Effect of Baicalein in Cancer-Induced Bone Pain, Evidence-Based Complementary and Alternative Medicine, 2015, 2015, DOI: 10.1155/2015/973524