Institute of Bioscience & Integrative Medicine, Daejeon University, Daejeon University, Daejeon, 35235, Republic of Korea.
National Institute for Korean Medicine Development, Gyeongsan-si, 38540, Republic of Korea.
J Ethnopharmacol. 2021 Mar 1;267:113470. doi: 10.1016/j.jep.2020.113470. Epub 2020 Oct 14.
Astragalus membranaceus (Fisch.) and Bunge and Paeonia japonica (Makino)Miyabe & H.Takeda have been traditionally used to improve the poor quality of life such as weakness, lack of appetite, fatigue, and malaise which is considered with cachexia condition.
We investigated anti-cachectic effects of a herbal formula composed of Astragalus membranaceus and Paeonia japonica (APX) and the molecular mechanisms of APX in C26 cancer-induced cachexia mice and TNF-a-treated C2C12 myotubes. Additionally synergistic anti-cachectic effects of APX were compared to those of individual herbal extracts and megestrol acetate.
The forty-two BALB/c mice were randomly divided into 6 groups: normal (nontreatment), control (C26 injection), AM (C26 injection with Astragalus membranaceus), PJ (C26 injection with Paeonia japonica), APX (C26 injection with combination of Astragalus membranaceus and Paeonia japonica and MA (C26 injection with megestrol acetate). All mice were orally administered DW (normal and control groups) or 100 mg/kg AM, PJ, APX or MA for 10 days. In the animal model, several tissues were weighed, and muscle tissue and blood were used to measure pro-inflammatory cytokines. C2C12 myotubes were exposed to 100 ng/mL TNF- α with or without 10 μg/mL of AM, PJ, APX or MA for 48 h. The cells were used to immunofluorescence staining and western blot analyses.
C26 injection induced notable body and muscle weight loss while APX administration significantly attenuated these alterations and the decrease of muscle weights and strength. APX also significantly attenuated the abnormal elevations in the concentration of three muscle atrophy-inducible cytokines; serum and muscle TNF-α,muscle TWEAK and IL-6 in C26 tumor-bearing mice. In the TNF-α-treated C2C12 myotube model, TNF-α treatment notably decreased MyH but activated atrophic proteins (MuRF and Fbx32) along with p38 and NFκB while these molecular alterations were significantly ameliorated by APX treatment. These pharmacological actions of APX were supported by the results of immunofluorescence staining to MyH expression and the translocation of NFκB into the nucleus in C2C12 myotubes.
Our data indicate the potential of an herbal formula, APX as an anti-cachexia agent; the effect of APX was superior to that of megestrol acetate overall especially for muscle atrophy. The underlying mechanisms of this herbal formula may involve the modulation of muscle atrophy-promoting molecules including p38, NFκB, TNF-α and TWEAK.
黄芪（膜荚黄芪）和芍药（牡丹）传统上被用于改善生活质量差，如虚弱、食欲不振、疲劳和不适，这些被认为是恶病质的表现。
本研究旨在探讨黄芪和芍药（APX）组成的中草药配方对 C26 癌诱导恶病质小鼠和 TNF-α处理的 C2C12 肌管的抗恶病质作用及其分子机制。此外，还比较了 APX 与单一草药提取物和甲地孕酮的协同抗恶病质作用。
42 只 BALB/c 小鼠随机分为 6 组：正常（未治疗）、对照（C26 注射）、AM（C26 注射加黄芪）、PJ（C26 注射加芍药）、APX（C26 注射加黄芪和芍药）和 MA（C26 注射加甲地孕酮）。所有小鼠连续 10 天口服 DW（正常和对照）或 100mg/kg AM、PJ、APX 或 MA。在动物模型中，称取几种组织的重量，并测量肌肉组织和血液中的促炎细胞因子。用 100ng/ml TNF-α处理 C2C12 肌管 48 小时，同时用 10μg/ml AM、PJ、APX 或 MA 处理。将细胞用于免疫荧光染色和 Western blot 分析。
C26 注射导致显著的体重和肌肉重量减轻，而 APX 给药显著减轻了这些变化以及肌肉重量和强度的降低。APX 还显著降低了肌肉萎缩诱导细胞因子的异常升高；血清和肌肉 TNF-α、肌肉 TWEAK 和 IL-6 在 C26 肿瘤荷瘤小鼠中。在 TNF-α处理的 C2C12 肌管模型中，TNF-α处理显著降低了 MyH，但激活了萎缩蛋白（MuRF 和 Fbx32）以及 p38 和 NFκB，而 APX 处理显著改善了这些分子改变。APX 的这些药理作用得到了 C2C12 肌管中 MyH 表达的免疫荧光染色和 NFκB 向核内易位的结果支持。
我们的数据表明，一种草药配方 APX 作为一种抗恶病质药物具有潜力；APX 的效果总体上优于甲地孕酮，尤其是对肌肉萎缩。该草药配方的作用机制可能涉及调节包括 p38、NFκB、TNF-α和 TWEAK 在内的肌肉萎缩促进分子。
