Magnolol Attenuates Cisplatin-Induced Muscle Wasting by M2c Macrophage Activation

Abstract

Cancer chemotherapy induces sarcopenia, which is a rapid loss of muscle mass that directly restricts daily activities and leads to poor quality of life and increased mortality. Although hormone-related therapies have been used to improve appetite and nutritional status, current treatments are considered palliative. Thus, the protection of skeletal muscle loss without adverse effects is essential to allow the maintenance of chemotherapy in cancer patients. Magnolol from Magnolia officinalis has several pharmacological effects including anti-cancer and anti-inflammatory activities, but the protection from muscle atrophy is not well-understood. In the present study, we investigated the effects of magnolol on muscle wasting and macrophage subtypes in a cisplatin-induced sarcopenia mouse model. We showed that magnolol significantly attenuated the body weight and the muscle loss induced by cisplatin injection. The diameter of the tibialis anterior muscle was markedly increased after magnolol treatment in cisplatin-treated mice. Importantly, magnolol increased macrophage infiltration into skeletal muscle while not affecting proliferation of macrophages. Magnolol attenuated the imbalance of M1/M2c macrophages by increasing CD206 + CD163 + M2c tissue reparative macrophages. Further, magnolol increased insulin-like growth factor (IGF)-1 expression. This effect was also observed in bone marrow-derived macrophages upon magnolol treatment. Taken together, magnolol may be a promising chemoprotective agent for the prevention of muscle atrophy through the upregulating M2c macrophages, which are a major source of IGF-1.

Crosstalk Between Skeletal Muscle and Immune System: Which Roles Do IL-6 and Glutamine Play?

“…Once monocytes become resident cells, they also express different phenotypes depending on their activation state (Lee et al, 2020). They co-express CD11b and CD206 and participate in tissue repair by secreting chemotactic factors, having low phagocytic property (Dort et al, 2019).…”

“…M2 macrophages are responsible for regulating the tissue repair process (Dort et al, 2019;Wang et al, 2014). In fact, M1 and M2 act in a perfect balance and together are responsible for the skeletal muscle homeostasis (Lee et al, 2020). Lemos et al (2015) showed that skeletal muscle resident M1 and M2 macrophage-produced cytokines modulate the extracellular matrix production through the fibro/adipogenic progenitor cells (FAPs).…”

“…M2 macrophages can be divided into three subsets, each one depending on a specific polarization signal. IL-4 and IL-13 exposure activates M2a macrophages, while M2b polarization happens through Il-1 receptor ligands, and M2c polarization is promoted by IL-10 and glucocorticoids ( Dort et al, 2019 ; Lee et al, 2020 ). M2 macrophages are responsible for regulating the tissue repair process ( Dort et al, 2019 ; Wang et al, 2014 ).…”

“…M2 macrophages are responsible for regulating the tissue repair process ( Dort et al, 2019 ; Wang et al, 2014 ). In fact, M1 and M2 act in a perfect balance and together are responsible for the skeletal muscle homeostasis ( Lee et al, 2020 ).…”

Advance in Drug Delivery for Ageing Skeletal Muscle

“…More importantly, doxorubicin may cause the absent of M1 macrophage during the inflammatory phase . Lee, C. et al found Magnolol, a kind of anti-cancer drug, could attenuate the imbalance of M1/M2c macrophages to inhibit muscle loss (Lee et al, 2020). Further, Liao, Z.H., et al found that regulating the functions of Treg cells would also be an important measure to promote muscle regeneration.…”