Journal of Natural Medicines ( IF 2.5 ) Pub Date : 2022-02-18 , DOI: 10.1007/s11418-022-01606-5 Taishi Kondo 1 , Tomoaki Ishida 1 , Ke Ye 1 , Marin Muraguchi 1 , Yohei Tanimura 1 , Masato Yoshida 1 , Kan'ichiro Ishiuchi 1 , Tomoki Abe 2 , Takeshi Nikawa 3 , Keisuke Hagihara 4 , Hidetoshi Hayashi 5 , Toshiaki Makino 1
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Processed aconite root (PA), the tuberous root of Aconitum carmichaelii prepared by autoclaving, is a crude drug used in Japanese traditional Kampo medicine and traditional Chinese medicine for the symptoms of kidney deficiency, that is related to the muscle atrophy in modern medicine. The objective of the present study is to evaluate the effectiveness of PA on muscle atrophy and to find its active ingredients using dexamethasone-induced muscle ring finger protein-1 (MuRF1) mRNA expression in murine myoblast C2C12 cells. Dexamethasone-induced MuRF1 expression was significantly suppressed by methanol-soluble part of boiling water extract of PA in a concentration-dependent manner with its IC50 value of 1.5 mg/ml. By the activity-guided fractionations of PA extract using the partition between organic solvents and its aqueous solution, the activity of PA did not transfer into the fraction containing aconitine-type diterpenoid alkaloids but into BuOH layer. Then, we found higenamine and salsolinol as the active ingredients in PA. Higenamine and salsolinol significantly suppressed dexamethasone-induced MuRF1 expression, and their IC50 values were 0.49 and 50 µM, respectively. The contents of higenamine and salsolinol in the decoctions of commercially available fourteen PA products are 0.12 and 14 µg/ml as the average values, and varied with the coefficient of variation (CV) values of 97 and 63%, respectively. Higenamine also significantly suppressed dexamethasone-induced mRNA expressions of muscle atrophy F-box protein (MAFbx)/atrogin1, casitas B-lineage lymphoma-b (Cbl-b), troponin, branched-chain amino acid aminotransferase 2 (BCAT2), and Bcl-2 binding and pro-apoptotic protein3 (Bnip3). Although the quality control of PA is regulated by the contents of diterpene alkaloids, salsolinol and higenamine can be used as the marker compounds to certificate the pharmacological activities of PA.
Graphical abstract
中文翻译：
炮制附子对地塞米松诱导的肌肉环指蛋白-1表达的抑制作用及其有效成分
附子根（Processed aconite root, PA），通过高压灭菌法制备的乌头的块根，是日本传统汉方医学和中医学中用于治疗肾虚症状的生药，在现代医学中与肌肉萎缩有关。本研究的目的是评估 PA 对肌肉萎缩的有效性，并使用地塞米松诱导的肌肉无名指蛋白 1 (MuRF1) mRNA 在小鼠成肌细胞 C2C12 细胞中的表达来寻找其活性成分。地塞米松诱导的 MuRF1 表达被 PA 沸水提取物的甲醇可溶部分以浓度依赖性方式显着抑制，其 IC 50值为 1.5 毫克/毫升。通过使用有机溶剂及其水溶液之间的分配对 PA 提取物进行活性引导分级，PA 的活性不会转移到含有乌头碱型二萜类生物碱的部分，而是转移到 BuOH 层中。然后，我们在 PA 中发现了去甲乌药碱和 salsolinol 作为活性成分。去甲乌药碱和 salsolinol 显着抑制地塞米松诱导的 MuRF1 表达及其 IC 50值分别为 0.49 和 50 µM。市售 14 种 PA 产品煎剂中去甲乌药碱和红木酚的含量平均值分别为 0.12 和 14 µg/ml，变异系数 (CV) 值分别为 97 和 63%。去甲乌药碱还显着抑制地塞米松诱导的肌肉萎缩 F-box 蛋白 (MAFbx)/atrogin1、casitas B 系淋巴瘤-b (Cbl-b)、肌钙蛋白、支链氨基酸转氨酶 2 (BCAT2) 和 Bcl 的 mRNA 表达-2 结合和促凋亡蛋白 3 (Bnip3)。虽然PA的质量控制受二萜类生物碱含量的影响，但红木酚和去甲乌药碱可以作为标志化合物来证明PA的药理活性。
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