Abstract
Cachexia causes high mortality, low quality of life, and rapid weight loss in cancer patients. Sarcopenia, a condition characterized by the loss of muscle, is generally present in cachexia and is associated with inflammation. M2 macrophages, also known as an anti-inflammatory or alternatively activated macrophages, have been shown to play a role in muscle repair. Magnoliae Cortex (M.C) is a widely used medicinal herb in East Asia reported to have a broad range of anti-inflammatory activities; however, the effects of M.C on sarcopenia and on M2 macrophage polarization have to date not been studied. This study was designed to investigate whether the oral administration of M.C could decrease cisplatin-induced sarcopenia by modulating M2 macrophage polarization in mice. C57BL/6 mice were injected intraperitoneally with cisplatin (2.5 mg/kg) to mimic chemotherapy-induced sarcopenia. M.C extract (50, 100, and 200 mg/kg) was administered orally every 3 days (for a total of 12 times). M.C (100 and 200 mg/kg) significantly alleviated the cisplatin-induced loss of body mass, skeletal muscle weight, and grip strength. In addition, M.C increased the expression of M2 macrophage markers, such as MRC1, CD163, TGF-β, and Arg-1, and decreased the expression of M1-specific markers, including NOS2 and TNF-α, in skeletal muscle. Furthermore, the levels of like growth factor-1(IGF-1), as well as the number of M2a and M2c macrophages, significantly increased in skeletal muscle after M.C administration. M.C did not interfere with the anticancer effect of cisplatin in colon cancer. Our results demonstrated that M.C can alleviate cisplatin-induced sarcopenia by increasing the number of M2 macrophages. Therefore, our findings suggest that M.C could be used as an effective therapeutic agent to reverse or prevent cisplatin-induced sarcopenia.
Highlights
Sarcopenia is defined as a loss of muscle mass and strength and is one of the features of cachexia
We verified the presence of two major compounds in M.C, honokiol and magnolol, by comparing the retention time and UV spectra of standard compounds using the established high pressure liquid chromatography (HPLC) protocol (Figure 1)
Our results demonstrated that the expression of M1 markers (TNF-α and iNOS) was increased in the cisplatin-treated group; the M.C treatment decreased their expression (Figure 4A,B)
Summary
Sarcopenia is defined as a loss of muscle mass and strength and is one of the features of cachexia. It has been shown that inflammatory cytokines, such as TNF-α, play an important role in muscle wasting in sarcopenia [5]. M1 macrophages by macrophage polarization produce pro-inflammatory cytokines, such as IL-1, TNF-α, and IL-6, causing muscle wasting and increasing protein degradation via the lysis of muscle fibers [10]. M2 macrophages secrete several anti-inflammatory cytokines, such as TGF-β and IL-10, leading to muscle recovery and regeneration, and the acceleration of muscle fiber synthesis. Honokiol has been reported to inhibit the LPS-induced TNF-α secretion in macrophages and to exhibit anti-cancer activity [23]. It is not known whether M.C, which contains magnolol and honokiol, has a therapeutic effect on sarcopenia. We assessed the effect of M.C treatment on cisplatin-induced tumor formation
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