Atractylodin alleviates cancer anorexia-cachexia syndrome by regulating NPY through hypothalamic Sirt1/AMPK axis-induced autophagy.

Cancer anorexia-cachexia syndrome (CACS) is a complex syndrome associated with loss of muscle and adipose tissue and weight loss, and is a major lethal factor in the later stages of cancer. The mechanism of action of CACS is not fully understood and there are no drugs specifically approved for its treatment. Atractylodin, the main active component of Atractylodes lancea, is widely used in the treatment of digestive disorders and has the ability to reduce IL-1, IL-6 and TNF-α levels. Our results showed that gavage with Atractylodin increased body weight, muscle and fat weight and reduced tumor weight and volume as well as abnormally high serum concentrations of the muscle atrophy-causing cytokines IL-1ß, IL-6 and TNF-α in CACS model mice. RT-PCR data revealed that Atractylodin promoted the expression of the pro-feeding NPY and suppressed the expression of the anorexia POMC in the hypothalamus. Western blot results showed that Atractylodin promoted the expression of Sirt1 and p-AMPK in the hypothalamus, accompanied by an increase in autophagy. Furthermore, the Sirt1 inhibitor EX527 or AMPK inhibitor Compound C (CC) reversed Atractylodin-induced beneficial effects in CACS model mice. In hypothalamic cells subjected to glucose deprivation, Atractylodin increased NPY mRNA expression by enhancing AMPK-modulated autophagy; while EX527 or Compound C blunted Atractylodin-induced autophagy enhancement effect in vitro. In conclusion, Atractylodin can be used as an anti-cachexia drug and the underlying mechanism may involve the promotion of NPY expression by Sirt1/AMPK-regulated autophagy.

Atorvastatin Treatment for Atrial Fibrillation Reduces Serum High-Sensitivity C-Reactive Protein Levels.

We investigated whether serum hs-CRP levels predict the efficacy of atrial fibrillation (AF) treated with atorvastatin. Bibliographic databases were exhaustively searched for studies relevant to the research topic. Newcastle-Ottawa Scale (NOS) criteria, combined with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS), were applied for study quality assessment. Our meta-analysis identified seven cohort studies (2006~2013), providing information on the change in serum hs-CRP levels in AF patients receiving atorvastatin therapy. After atorvastatin treatment, hs-CRP level in AF patients decreased significantly (SMD = 1.02, 95% CI: 0.58-1.47, P < 0.001). Subgroup analysis by country and hs-CRP detection methods suggested a negative relationship between atorvastatin treatment and hs-CRP levels among Chinese AF patients (SMD = 1.34, 95% CI: 1.00-1.69, P < 0.001) and by using ELISA method (SMD = 1.11, 95% CI: 0.51-1.71, P < 0.001), but not among Turkish population and using INA method (all P > 0.05). Egger's test showed no publication bias (P = 0.450). hs-CRP was clearly lowered in AF patients treated with atorvastatin, which may be helpful in the choice of statin agents for AF treatment. However, longer follow-ups are necessary to assess the clinical value of lowering hs-CRP in the clinical setting of AF treatment outcomes.

Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy.

Diabetic nephropathy (DN) is an important diabetic complication, and podocyte apoptosis plays a critical role in the development of DN. In the present study, we examined the preventive effect of the total flavone glycosides of Flos Abelmoschus manihot (TFA) on urinary microalbumin and glomerular podocyte apoptosis in experimental DN rats. The preliminary oral administration of TFA (200 mg/kg/day) for 24 weeks significantly decreased the urinary microalbumin to creatinine ratio and 24-h urinary total protein in streptozotocin-induced DN rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay indicated glomerular cell apoptosis in DN rats was significantly improved by pretreatment with TFA. Furthermore, fluorescence-activated cell sorting and Hoechst 33342 staining suggested preincubation with hyperoside (50 and 200 µg/mL), the major active constituent of TFA, could significantly mitigate cultured podocyte apoptosis induced by the advanced glycation end-products (AGEs). Western blot analysis showed that increased caspase-3 and caspase-8 expressions induced by AGEs were also inhibited by pretreatment with hyperoside at both doses. Our results demonstrate that TFA pretreatment can decrease urinary albumin excretion in early-stage DN, which might be accomplished by preventing renal damage and podocyte apoptosis.