Fig 1.
Effects of magnolol on body weight, daily food intake and tumor growth.
The chemical structure of magnolol (A) and the experimental design of this study (B) were shown. The body weight (C) daily food intake (D) and bladder weight (E) in different groups were measured. Data was expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01 versus normal group. #P < 0.05 versus TGC group.
Table 1.
The antibodies used in this study.
Fig 2.
Effects of magnolol on intestinal damage and digestive enzyme dysfunction.
The morphological changes in intestinal structure and the grading score were evaluated (A). The intestinal digestive enzyme activity in different groups was determined (B). Data was expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 versus normal group. #P < 0.05, ##P < 0.01 versus TGC group.
Fig 3.
Effects of magnolol on muscle atrophy, proteasome activity and atrogenic gene expression.
The images of the muscle of limb and the weight of gastrocnemius and soleus muscle were photographed or measured (A). The proteasome activity (B), the levels of myostatin, and activin A (C), and the protein expression of atrogenic genes (D) in muscle were determined. Data was expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 versus normal group. #P < 0.05, ##P < 0.01, ###P < 0.001 versus TGC group.
Fig 4.
Effects of magnolol on atrogenic gene expression and IGF-1-regulated protein synthesis signaling.
The amounts of FoxO3, MuRF-1 and MAFbx determined by immunofluorescence staining (A) and the IGF-1 levels and related protein synthesis signaling pathway in muscle of various groups were determined (B). Data was expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 versus normal group. #P < 0.05, ##P < 0.01, ###P < 0.001 versus TGC group.
Fig 5.
Effects of magnolol on pro-inflammatory cytokine production and NF-κB activation.
The serum levels (A) and the protein expression of pro-inflammatory cytokines, CRP and phospho-NF-κB in muscle (B) were measured. Data was expressed as mean ± SEM (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 versus normal group. #P < 0.05, ##P < 0.01 versus TGC group.
Fig 6.
The proposed schematic diagram of signaling pathways for the anti-cachectic activity of magnolol.
Combined treatment with magnolol inhibits myostatin/activin/FoxO3 cascade, proinflammatory cytokine formation, and NF-κB activation, leading to suppressing ubiquitin E3 (MAFbx and MuRF1) expression, and proteasome activity, which in turn attenuates the muscle protein proteolysis. Meanwhile, enhancing protein synthesis through activation of IGF-1-regulated signaling, and preventing intestinal damage and anorexia may also contribute to its protective effect. Taken together, magnolol may be a potential supplement for reducing muscle atrophy associated with cancer cachexia during chemotherapy.