# Extract of Litsea japonica (Thunba.) Jussieu Fruit Reduces Muscle Atrophy in Cancer Cachexia

## TL;DR

Litsea japonica fruit extract, especially the ethanol extract, reduces muscle atrophy in cancer cachexia by targeting myostatin and related proteins.

## Contribution

This is the first study to investigate the effects of Litsea japonica fruit extract on cancer cachexia.

## Key findings

- LJFE-E reduced muscle atrophy in C2C12 myotubes and C26 tumor-bearing mice by inhibiting MSTN, MuRF1, and MAFbx32.
- LJFE-E and LJFE-W activated the Akt–mTOR pathway to promote protein synthesis in myotubes.
- LJFE-E injection lowered MSTN-related gene expression in gastrocnemius muscles of tumor-bearing mice.

## Abstract

Cancer cachexia is a complex syndrome involved in muscle wasting, fat depletion, fatigue, reduced appetite, and unintentional weight loss. Recent studies have suggested that natural products can prevent cancer cachexia; however, there have been no studies on the effects of Litsea japonica fruit extract on cancer cachexia. This study aimed to identify compounds of
L. japonica
fruit extracted from water (LJFE‐W) and those extracted from 30% ethanol (LJFE‐E) for cancer cachexia treatment. In vitro and in vivo models were used for C26 conditioned medium (CM)‐induced C2C12 myotubes and C26 tumor‐bearing mice. We demonstrated that LJFE‐W and LJFE‐E regulated myostatin (MSTN), E3 ligase muscle‐specific RING finger protein‐1 (MuRF1), and muscular atrophy fbox‐1 protein (MAFbx32) expression in a CM‐induced in vitro model. LJFE‐E ameliorated conditioned medium‐induced myotube atrophy in cultured C2C12 myotubes. In contrast, LJFE‐W and LJFE‐E stimulated the Akt–mTOR signaling pathway for protein synthesis in C2C12 myotubes. In animal models, the LJFE‐E‐injected C26 tumor‐bearing group showed lower transcript‐level expression of MSTN, MuRF1, and MAFbx32 in the gastrocnemius muscles than the C26 tumor‐bearing group. LJFE ameliorated muscle atrophy in the cancer cachexia model by inhibiting MSTN. Thus, LJFE can be used as a supplement to cancer cachexia therapy.

This study demonstrated that Litsea japonica fruit extract (LJFE), especially LJFE‐E (30% ethanol extract), alleviated muscle atrophy by modulating myostatin (MSTN) in vitro and in vivo cancer cachexia models. These findings highlight LJFE as a promising supplement for cancer cachexia.