To investigate the transport mechanism of isorhynchophylline (IRN) by using the specific inhibitors of organic cation transporters (OCTs) and organic anion transporting polypeptides (OATPs) and attempt illustrate the metabolic mechanism of IRN in the liver. All animals were randomly divided into three groups: control group (only inject IRN), RIF group (inject IRN and rifampicin), and ADR group (inject IRN and adrenalone). The control group was injected with IRN via the caudal vein. The RIF group was injected with rifampicin (RIF) by gavage, and after 1 h, IRN was injected into the caudal vein. Similarly, the ADR group received adrenalone by the caudal vein, and after 0.5 h, IRN was injected into the caudal vein. Thereafter, blood samples were obtained by the heart punctures at 90 min, 180 min, and 300 min following drug administration. Rats were sacrificed at 300 min after drug administration; then, the liver tissue was harvested. The level of IRN was measured by using high-performance liquid chromatography (HPLC), and the Kp values were calculated. After RIF administration (OATPs inhibitors), the Kp value of IRN was slightly decreased when compared with that of the control group. Meanwhile, the Kp value of IRN was dramatically reduced compared to that of the control group following ADR administration (OCTs inhibitors). The results suggested that OCTs have mainly participated in the hepatic uptake process of IRN.

BACKGROUND: Sarcopenia is a symptom of muscle aging characterized by mass loss and strength loss. The disorder is the leading cause of fall incapacity/death in the elderly and the great enemy of healthy aging. Energy deprivation (calorie restriction and exercise) is the most effective means against aging and SIRT1 is a key mediator molecule. OBJECTIVE: The article summarizes and analyzes the mechanisms of SIRT1-mediated energy deprivation against sarcopenia/skeletal muscle aging. METHODS: Literature review. CONCLUSIONS: Exercise and Calorie restriction lead to intermittent and continuous energy deprivation in muscle, respectively, which may contribute to some differences in their effects and mechanisms. SIRT1 may reside centrally in energy deprivation against sarcopenia. AMPK/NAD + is the bridge between energy deprivation and SIRT1 activation. SIRT1 downstream is mainly through four pathways (FOXO1/autophagy, PGC-1α/mitochondrial generation, P53/apoptosis and DNA repair, and NF-κB/inflammation) to antagonize muscle aging/sarcopenia. Future directions to focus on: (1) Difference between the mechanisms of SIRT1 under stresses of exercise and calorie restriction. ( 2) The role of non-transcription factor targets of SIRT1 such as eNOS, LKB1, etc. 3) Exact division of labor involved in several cellular event molecules simultaneously, such as FOXO1, NF-κB and P53.