Department of Orthopedic Surgery, Wenzhou People's Hospital, Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Third Affiliated Hospital of Shanghai University, No.57 Canghou Street, Wenzhou, Zhejiang, PR China.
Department of Orthopedic Surgery, Mindong Hospital Affiliated to Fujian Medical University, No.89 Heshan Road, Fuan, Fujian, PR China.
Biochem Biophys Res Commun. 2023 Dec 31;689:149235. doi: 10.1016/j.bbrc.2023.149235. Epub 2023 Nov 10.
Salvia miltiorrhiza Bunge is a widely-used traditional Chinese medicine to treat a variety of diseases including muscle disorders. The underlying pharmacological mechanisms of which active component and how it functions are still unknown. Tanshinone IIA (Tan IIA) is the main active lipophilic compound in Salvia miltiorrhiza Bunge. Muscle stem cells (MuSCs) play a crucial role in maintaining healthy physiological function of skeletal muscle. For the purpose of this study, we investigated the effects of Tan IIA on primary MuSCs as well as mechanism. The EdU staining, cell counts assay and RT-qPCR results of proliferative genes revealed increased proliferation ability of MuSCs after Tan IIA treatment. Immunofluorescent staining of MyHC and RT-qPCR results of myogenic genes found Tan IIA contributed to promoting differentiation of MuSCs. In addition, enrichment analysis of RNA-seq data and Western blot assay results demonstrated activated MAPK and Akt signaling after treatment of Tan IIA during proliferation and differentiation. The above proliferative and differentiative phonotypes could be suppressed by the combination of MAPK inhibitor U0126 and Akt inhibitor Akti 1/2, respectively. Furthermore, HE staining found significantly improved myofiber regeneration of injured muscle after Tan IIA treatment, which also contributed to muscle force and running performance recovery. Thus, Tan IIA could promote proliferation and differentiation ability of MuSCs through activating MAPK and Akt signaling, respectively. These beneficial effects also significantly contributed to muscle regeneration and muscle function recovery after muscle injury.
丹参是一种广泛应用于治疗多种疾病的传统中药，包括肌肉疾病。其有效成分的潜在药理机制及其作用方式尚不清楚。丹参酮 IIA（Tan IIA）是丹参中的主要脂溶性活性化合物。肌肉干细胞（MuSCs）在维持骨骼肌的健康生理功能方面起着至关重要的作用。为了进行本研究，我们研究了 Tan IIA 对原代 MuSCs 的影响及其作用机制。EdU 染色、细胞计数和增殖基因的 RT-qPCR 结果表明，Tan IIA 处理后 MuSCs 的增殖能力增强。MyHC 的免疫荧光染色和肌生成基因的 RT-qPCR 结果发现，Tan IIA 有助于促进 MuSCs 的分化。此外，RNA-seq 数据的富集分析和 Western blot 检测结果表明，在增殖和分化过程中，Tan IIA 处理后 MAPK 和 Akt 信号被激活。上述增殖和分化表型可分别被 MAPK 抑制剂 U0126 和 Akt 抑制剂 Akti 1/2 抑制。此外，HE 染色发现，Tan IIA 处理后损伤肌肉的肌纤维再生明显改善，这也有助于肌肉力量和跑步性能的恢复。因此，Tan IIA 可以通过激活 MAPK 和 Akt 信号分别促进 MuSCs 的增殖和分化能力。这些有益作用也显著促进了肌肉损伤后的肌肉再生和肌肉功能恢复。
