Kampo formula hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang, TJ-41) ameliorates muscle atrophy by modulating atrogenes and AMPK in vivo and in vitro.

BACKGROUND: Muscle disuse results in loss of skeletal muscle mass and function. Hochu-ekki-to (TJ-41; Bu-Zhong-Yi-Qi-Tang in Chinese) is an herbal medicinal formulation used to treat patients with frailty, fatigue and appetite loss. It has been suggested that two atrogenes, atrogin-1 and muscle Ring finger 1 (MuRF1), are ubiquitin ligases involved in disuse-induced muscle atrophy and that 5' adenosine monophosphate-activated protein kinase (AMPK) is involved in skeletal muscle metabolism. Effects of TJ-41 on disuse-induced muscle atrophy are unclear. METHODS: We subjected differentiated C2C12 myotubes to serum starvation, then examined the effects of TJ-41 on atrogenes expression, AMPK activity and the morphology of the myotubes. Male C57BL/6J mice were subjected to tail-suspension to induce hindlimb atrophy. We administered TJ-41 by gavage to the control group and the tail-suspended group, then examined the effects of TJ-41 on atrogene expression, AMPK activity, and the muscle weight. RESULTS: Serum starvation induced the expression of atrogin-1 and MuRF1 in C2C12 myotubes, and TJ-41 significantly downregulated the expression of atrogin-1. Tail-suspension of the mice induced the expression of atrogin-1 and MuRF1 in skeletal muscle as well as its muscle atrophy, whereas TJ-41 treatment significantly downregulated the expression of atrogin-1 and ameliorated the loss of the muscle weight. In addition, TJ-41 also activated AMPK and inactivated Akt and mTOR in skeletal muscle in vivo. CONCLUSION: TJ-41 inhibited atrogenes in an Akt-independent manner as well as activating AMPK in skeletal muscles in vivo, further implying the therapeutic potential of TJ-41 against disuse-induced muscle atrophy and other atrogenes-dependent atrophic conditions.

miR-19a-3p Functions as an Oncogene by Regulating FBXO32 Expression in Multiple Myeloma.

BACKGROUND: Multiple myeloma remains a virtually incurable hematologic malignancy, which is featured with the aberrant growth of malignant plasma cells. AIMS: To elucidate the functions of miR-19a-3p in multiple myeloma. STUDY DESIGN: Cell study. METHODS: Cell counting kit-8 assay was performed to detect cell viability, and flow cytometry was conducted to detect cell apoptosis. Bioinformatics analysis predicted miR-19a-3p-associated biological function, pathway, core regulatory network, and target genes. Luciferase reporter assay verified the target sequence of miR-19a-3p regulating FBXO32. RESULTS: miR-19a-3p is upregulated in multiple myeloma cells (p<0.01) and patients with multiple myeloma (p<0.001). Overexpressed miR-19a-3p significantly increased cell viability (p<0.05) and inhibited cell apoptosis (p<0.01). FBXO32 is a target gene of miR-19a-3p (p<0.01). Moreover, FBXO32 is downregulated in MM, and it significantly decreased cell viability (p<0.05) and promoted cell apoptosis (p<0.01). FBXO32 significantly rescued the influence of miR-19a-3p-inhibiting cell apoptosis (p<0.05). CONCLUSION: miR-19a-3p promoted cell proliferation and inhibited cell apoptosis by degrading the target FBXO32 mRNA in multiple myeloma.