Huangqi Guizhi Wuwu Decoction Ameliorates Cachexia in Lung Cancer Mice Through Regulating Amino Acid Metabolism: Insights From Transcriptomics, Metabolomics and Experimental Validation

Abstract

The effects and mechanisms of Huangqi Guizhi Wuwu Decoction (HGWD) in cancer cachexia remain unclear. We generated an in vivo cachexia model by implanting Lewis lung carcinoma cells into mice and treated animals with HGWD. We evaluated muscle function using grip strength and wire-grip tests. We also assayed markers of muscle synthesis and oxidative stress, and assessed tumour growth to evaluate any antitumor effects of HGWD. Finally, we performed transcriptomic and untargeted metabolomic analyses. HGWD increased muscle strength and restored muscle mass in cachectic mice. HGWD improved levels of proteins associated with muscle anabolism and altered oxidative stress–related factors. Treated mice showed modest tumour inhibition and greater food and water intake. Transcriptomic profiling of gastrocnemius muscle revealed significant enrichment of amino acid–related metabolic pathways after HGWD treatment. Untargeted metabolomics indicated that most branched-chain amino acids were upregulated following HGWD intervention. Further validation showed that HGWD increased both gene and protein expression of adenosylmethionine decarboxylase 1 (AMD1) and spermine oxidase (SMOX), while decreasing gene and protein expression of glycine N-methyltransferase (GNMT) in the gastrocnemius of cachectic mice. The anti-cancer cachexia effect of HGWD appears to be associated with promoting the conversion of S-adenosylmethionine (SAM) to spermidine, thereby correcting amino acid metabolic disturbances.