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.

Alzheimer’s disease (AD) is characterized by progressive cognitive and functional loss leading to neurodegeneration. Although the details are unclear, recent substantial literature suggest that neuroinflammation can facilitate or initiate neurodegeneration of AD. We previously reported the therapeutic potential of regulatory T cells (Tregs) modulating neuroinflammation to protect cells against neurodegeneration. This study assessed the impact of regulatory T cells in the context of Alzheimer’s diseases and investigated the therapeutic effects by adoptive cell therapy with Tregs. When regulatory T cells were administered in the 3xTg animal model of AD, cognitive impairment was markedly improved. Microglial activation and reactive astrocyte in AD mice were dramatically abolished after a single injection of adoptive transfer of regulatory T cells. We confirmed these therapeutic potential of adoptive transfer of Tregs in intraventricular amyloid-β-injected mice model. Altogether, our studies suggest that regulatory T cell adoptive transfer may alleviate neurodegeneration of Alzheimer’s disease (AD).

Background Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes cognitive impairment. Neuroinflammation induced by activated microglia exacerbates AD. Regulatory T cells (Tregs) play roles in limiting neuroinflammation by converting microglial polarization. Therefore, adoptive regulatory T cell therapy is considered an attractive option for neurodegenerative disorders. However, the mechanism underlying Treg therapy via microglial modulation is not fully understood. In this study, we sought to determine whether adoptively transferred Tregs were effective when microglia were depleted by CSF-1R inhibition. Methods First, we inhibited microglial proliferation using GW2580, a CSF-1R inhibitor, when Tregs were transferred. Learning and memory were assessed using a passive avoidance test. The accumulation of Aβ and pTAU, a hallmark of AD, was measured using immunofluorescence. Microglial neuroinflammation was assessed using immunofluorescence and RT-PCR. To track adoptively transferred Tregs, Tregs from Thy1.1 mice were transferred to 3xTg-AD Thy1.2 mice and mouse tissues, including brains, were harvested after 3–112 days. Results We found that inhibition of microglial proliferation during Treg transfer did not alter the therapeutic effects of Tregs on cognitive deficits and the accumulation of Aβ and pTAU in 3xTg-AD mice. The expression of pro- and anti-inflammatory markers in the hippocampus of 3xTg mice showed that GW2580 did not affect the inhibition of neuroinflammation by Treg transfer. Additionally, adoptively transferred Tregs were commonly detected in the brain on day 7 after transfer and their levels decreased slowly over 100 days. Conclusions Together, these data suggest that adoptively transferred Tregs can survive longer than 100 days in the brain, suppressing microglial activation and thus alleviating AD pathology. The present study provides valuable evidence to support the prolonged efficacy of adoptive Treg therapy in AD.