# Systematic Exploration of Molecular Mechanisms and Natural Herbal Therapeutic Strategies for Cancer Cachexia

## TL;DR

This paper reviews how natural herbs can help treat cancer cachexia by targeting inflammation and muscle loss, offering safer alternatives to current drugs.

## Contribution

The paper systematically explores molecular mechanisms and natural herbal strategies for cancer cachexia, emphasizing their multi-target therapeutic potential.

## Key findings

- Natural herbs like Coicis Semen and Scutellaria baicalensis reduce inflammation and muscle atrophy in cancer cachexia.
- Herbal treatments modulate signaling pathways such as NF-κB and IL-6, showing minimal tumor suppression but significant anti-inflammatory effects.

## Abstract

Cachexia often occurs in many cancer patients at the terminal stage, which seriously affects their subsequent treatment and prognosis. Although currently commonly used clinical drugs have provided significant assistance, their limitations are also quite obvious. Many natural herbs possess the property of “medicine–food homology” and have a good safety profile, so incorporating them into the treatment of cachexia is highly valuable. Meanwhile, the multi-target characteristic of herbs enables them to target the immune–metabolic axis and alleviate cachexia.

Cancer cachexia (CC) is a multifactorial, multi-organ syndrome characterized by systemic inflammation, metabolic dysregulation, anorexia, and progressive depletion of skeletal muscle and adipose tissue. Despite its high prevalence among patients with advanced malignancies, effective therapeutic options remain limited. Recent studies have elucidated the molecular underpinnings of CC and the therapeutic potential of natural herbs, highlighting the involvement of central nervous system regulation, adipose tissue, immune responses, gut microbiota, skeletal muscle, and disruptions in anabolic–catabolic signaling pathways such as mTOR, UPS, NF-κB, and STAT3. Persistent inflammation induces E3 ubiquitin ligases (Atrogin-1/MuRF-1) through cytokines including IL-6 and TNF-α, thereby impairing muscle homeostasis, while suppression of anabolic cascades such as IGF-1/mTOR further aggravates muscle atrophy. The limited efficacy and adverse effects of synthetic agents like megestrol acetate underscore the value of herbal therapies as safer adjunctive strategies. Botanicals such as Coicis Semen, Scutellaria baicalensis, and Astragalus demonstrate anti-inflammatory and muscle-preserving activities by modulating NF-κB, IL-6, and oxidative stress signaling. Numerous investigations indicate that these herbs downregulate MuRF-1 and Atrogin-1 expression, enhance appetite, and attenuate muscle loss, though they exhibit minimal influence on tumor suppression. While promising, current evidence remains largely preclinical and mechanistic validation is incomplete. This review consolidates contemporary insights into CC pathogenesis and the bioactivity of herbal interventions, highlighting the need for translational research to bridge preclinical findings with clinical applicability.