Analgesic Effect of Boiogito, a Japanese Traditional Kampo Medicine, on Post-Traumatic Knee Osteoarthritis through Inhibition of ERK1/2 Phosphorylation in the Dorsal Horn of the Spinal Cord
Analgesic Effect of Boiogito, a Japanese Traditional Kampo Medicine, on Post-Traumatic Knee Osteoarthritis through Inhibition of ERK1/2 Phosphorylation in the Dorsal Horn of the Spinal Cord
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DOI：
10.3390/app11188421
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
Yusuke Kunieda;Takayuki Okumo;H. Ikemoto;Naoki Adachi;Midori Tanaka;Tarou Kimura;Kanako Yusa;K. Kanzaki;M. Sunagawa
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文献类型：
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作者：
Yusuke Kunieda;Takayuki Okumo;H. Ikemoto;Naoki Adachi;Midori Tanaka;Tarou Kimura;Kanako Yusa;K. Kanzaki;M. Sunagawa
保亿吉托（BO）是一种日本传统草药，已被证实对膝骨关节炎（KOA）相关疼痛具有临床疗效。然而，BO的治疗机制仍不明确。因此，我们利用大鼠膝骨关节炎模型探究了BO的镇痛机制。通过内侧半月板失稳（DMM）诱导大鼠患上膝骨关节炎。将大鼠分为以下四组：对照组、假手术组、DMM组以及DMM + BO组。采用转棒实验评估与疼痛相关的运动功能障碍。在DMM手术后第1天和第28天，通过免疫荧光染色和蛋白质免疫印迹法检测脊髓背角中磷酸化细胞外信号调节激酶1/2（pERK1/2）的表达。鞘内注射丝裂原活化蛋白激酶抑制剂U0126，然后进行转棒实验和蛋白质免疫印迹法检测。转棒实验显示，DMM组大鼠运动功能受损，而给予BO后运动功能显著改善。DMM组中pERK1/2阳性细胞数量增加，而DMM + BO组中该数量显著减少。U0126显著抑制ERK1/2磷酸化，并增加了转棒实验中的行走时间，这表明DMM相关疼痛与脊髓背角中ERK1/2磷酸化有关。总之，给予BO通过抑制ERK1/2磷酸化改善了与疼痛相关的运动功能障碍。
Boiogito (BO), a Japanese traditional herbal medicine, has been proven to be clinically effective against knee osteoarthritis (KOA)-associated pain. However, the therapeutic mechanism of BO remains unclear. Thus, we investigated the analgesic mechanism of BO using a rat KOA model. KOA was induced by destabilization of the medial meniscus (DMM). Rats were allocated into the following four groups: control, sham, DMM, and DMM + BO groups. Rotarod test was performed to evaluate the pain-related locomotive dysfunction. Expression of phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) in the spinal dorsal horn was examined using immunofluorescence staining and Western blotting on days 1 and 28 after DMM surgery. A mitogen-activated protein kinase inhibitor, U0126, was intrathecally injected and rotarod test and Western blotting were performed. The rotarod test revealed hampered locomotive function in the DMM group, which was significantly improved upon BO administration. The number of pERK1/2-positive cells was increased in the DMM group, whereas it was significantly decreased in the DMM + BO group. U0126 significantly inhibited ERK1/2 phosphorylation and increased walking time in the rotarod test, suggesting that the DMM-related pain was associated with ERK1/2 phosphorylation in the spinal dorsal horn. In conclusion, BO administration improved the pain-related locomotive dysfunction by suppressing ERK1/2 phosphorylation.