German Sports University Cologne, Department of Molecular and Cellular Sport Medicine, Cologne, Germany; Division of Sports and Rehabilitation Medicine, Center of Medicine, University Hospital Ulm, Ulm, Germany.
German Sports University Cologne, Department of Molecular and Cellular Sport Medicine, Cologne, Germany.
Toxicol Lett. 2023 Aug 15;385:21-28. doi: 10.1016/j.toxlet.2023.08.007. Epub 2023 Aug 19.
Higenamine (Hige), a plant derived alkaloid is classified as β2 agonist by the World Anti-Doping Agency (WADA). However, pharmacologic mechanisms of its performance-enhancing activity have not been investigated so far. Therefore, we investigate the anabolic activity and associated molecular mechanisms of Hige in C2C12 myotubes. In differentiated C2C12 cells dose-dependent effects of Hige on myotube size were analyzed. The mRNA expression of genes involved in hypertrophy was measured. For mechanistic studies, β2-adrenoceptor (ADRB2), androgen receptor (AR), and estrogen receptor (ER) inhibitors and dexamethasone (Dexa) were co-incubated and myotube diameter was evaluated. The interaction of Hige with the AR and ER was investigated. Hige treatment significantly increased myotube diameters and stimulated the mRNA expression of hypertrophy-involved genes. In contrast to the ADRB2 inhibitor (ICI 118551), the ER inhibitor ZK 191703, the AR inhibitor Flutamide (Flu), and treatment with Dexa were able to antagonize the Hige-induced increase of myotube diameter. Hige has antagonistic activity in the AR and ER yeast transactivation assay. Our results demonstrate that Hige induces anabolic effects in C2C12 cells but not via the ADRB2. There are indications for a cross talk between Hige and the AR and ER. Future studies are necessary to investigate the involved molecular mechanisms.
盐酸育亨宾（Hige）是一种植物衍生的生物碱，被世界反兴奋剂机构（WADA）归类为β2 激动剂。然而，其增强性能的药理学机制迄今尚未得到研究。因此，我们研究了 Hige 在 C2C12 肌管中的合成代谢活性及其相关的分子机制。在分化的 C2C12 细胞中，分析了 Hige 对肌管大小的剂量依赖性影响。测量了参与肥大的基因的 mRNA 表达。为了进行机制研究，共孵育了β2-肾上腺素能受体（ADRB2）、雄激素受体（AR）和雌激素受体（ER）抑制剂以及地塞米松（Dexa），并评估了肌管直径。研究了 Hige 与 AR 和 ER 的相互作用。Hige 处理显著增加了肌管直径并刺激了涉及肥大的基因的 mRNA 表达。与 ADRB2 抑制剂（ICI 118551）相反，ER 抑制剂 ZK 191703、AR 抑制剂氟他胺（Flu）和地塞米松处理能够拮抗 Hige 诱导的肌管直径增加。Hige 在 AR 和 ER 酵母转录激活测定中具有拮抗活性。我们的结果表明，Hige 在 C2C12 细胞中诱导合成代谢作用，但不是通过 ADRB2。有迹象表明 Hige 与 AR 和 ER 之间存在串扰。需要进一步的研究来探讨涉及的分子机制。
