4.6 Article

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

期刊

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.08.011

关键词

Atractylodin; Cancer anorexia-cachexia; Sirt1; AMPK; Autophagy

资金

  1. National Natural Science Founda- tion of China [81804035, 81904121]

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Atractylodin may be used as an anti-cachexia drug, with the underlying mechanism potentially involving the promotion of NPY expression through Sirt1/AMPK-regulated 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-alpha 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-1 beta, IL-6 and TNF-alpha 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.(C) 2022 Elsevier Inc. All rights reserved.

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