Cucurbitacin IIb attenuates cancer cachexia induced skeletal muscle atrophy by regulating the IL-6/STAT3/FoxO signaling pathway.

The main features of cancer cachexia include skeletal muscle atrophy, which can significantly reduce the quality of life of patients. Clinical treatment of cancer cachexia is mainly based on nutritional therapy and physical exercise; medication only improves appetite but does not reverse the symptoms of skeletal muscle wasting. In this work, we systematically studied the underlying molecular mechanisms by which cucurbitacin IIb (CuIIb) ameliorates muscle wasting in cancer cachexia both in vitro and in vivo. CuIIb significantly ameliorated the chief features of cancer cachexia in vivo, alleviating weight loss, food intake, muscle wasting, adipose tissue depletion, and organ weight reductions. In vitro, CuIIb (10 and 20 µM) dose-dependently attenuated conditioned medium (CM)-induced C2C12 myotube atrophy. Collectively, our findings demonstrated that CuIIb prevented the upregulation of the E3 ubiquitin ligase muscle atrophy Fbox protein (MAFbx), myosin heavy chain (MyHC), and myogenin (MyoG) and impacted protein synthesis and degradation. In addition, CuIIb decreased the phosphorylation of Tyr705 in STAT3 by regulating the IL-6/STAT3/FoxO pathway to reduce skeletal muscle atrophy in cancer cachexia.

Effect of Songlingxuemaikang on mild essential hypertension in patients: a randomized parallel-controlled study.

OBJECTIVE: To evaluate the effect of songlingxuemaikang (SLXMK) on mild essential hypertension in patients in terms of endothelial function. METHODS: We enrolled 90 patients with mild essential hypertension in Xuanwu Hospital from January 2016 to December 2016. To evaluate the effects of SLXMK, the 90 patients were randomly assigned at a 2∶1 ratio into 2 groups: the SLXMK group (500 mg per capsule, 4500 mg/d, n = 60) and the losartan potassium group (50 mg per table, 50 mg/d, n = 30). The total study period was 12 weeks, and the changes of blood pressure, laboratory test and endothelium function were compared between two groups. RESULTS: After 12 weeks of treatment with SLXMK, blood pressure (BP) and plasma lipid levels significantly improved (P < 0.05). Meanwhile, the reactive hyperemia index (RHI) increased in the SLXMK group (P < 0.05). The results of multivariate logistic regression analyses examining the association of selected variables with showed that high level of oxidized low density lipoprotein (ox-LDL) was positively associated with endothelial dysfunction. CONCLUSION: SLXMK not only effectively decreased BP and plasma lipid levels, but also reduced ox-LDL and RHI in patients with mild essential hypertension. And SLXMK might improve endothelial function through decreasing the circulating ox-LDL.

Daidzein alleviates cisplatin-induced muscle atrophy by regulating Glut4/AMPK/FoxO pathway.

Cisplatin (DDP) is widely used in cancer treatment, but DDP can cause skeletal muscle atrophy and cachexia. This study explored the effect and mechanism of daidzein (DAI) in reducing DDP-induced skeletal muscle atrophy and cachexia in vivo and in vitro. DAI alleviated the weight, food intake, muscle, adipose tissue, kidney weight and forelimb grip of LLC tumour-bearing mice after DDP treatment, and did not affect the antitumour effect of DDP. DAI can reduce the decrease of the cross-sectional area of skeletal muscle fibre-induced by DDP and prevent the change of fibre type proportion. In skeletal muscle, it can inhibit Glut4/AMPK/FoxO pathway, down-regulate the expression of atrogin1 and MuRF1, and inhibit skeletal muscle protein degradation. In DDP treated C2C12 myotubes, DAI could inhibit Glut4/AMPK/FoxO pathway to reduce myotubes atrophy, while AMPK agonist MK-3903 could reverse the protective effect of DAI. These results suggest that DAI can alleviate DDP-induced skeletal muscle atrophy by downregulating the expression of Atrogin1 and MuRF1 through the regulation of Glut4/AMPK/FoxO pathway.

Matrine: A Promising Natural Product With Various Pharmacological Activities.

Matrine is an alkaloid isolated from the traditional Chinese medicine Sophora flavescens Aiton. At present, a large number of studies have proved that matrine has an anticancer effect can inhibit cancer cell proliferation, arrest cell cycle, induce apoptosis, and inhibit cancer cell metastasis. It also has the effect of reversing anticancer drug resistance and reducing the toxicity of anticancer drugs. In addition, studies have reported that matrine has a therapeutic effect on Alzheimer's syndrome, encephalomyelitis, asthma, myocardial ischemia, rheumatoid arthritis, osteoporosis, and the like, and its mechanism is mainly related to the inhibition of inflammatory response and apoptosis. Its treatable disease spectrum spans multiple systems such as the nervous system, circulatory system, and immune system. The antidisease effect and mechanism of matrine are diverse, so it has high research value. This review summarizes recent studies on the pharmacological mechanism of matrine, with a view to providing reference for subsequent research.