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Cancer-associated depression accelerates tumor progression and worsens patient prognosis, yet conventional single-modality antitumor regimens fail to address this bidirectional pathology. Chronic low-grade inflammation triggered by gut microbiota dysbiosis acts as a shared pathological driver for both malignancy and depressive disorders, constituting a targetable gut microbiota–inflammation–depression axis. As a clinically approved natural antitumor agent with verified anti-inflammatory and microbiota-regulating properties, β-elemene shows promise for integrative cancer therapy, but its pharmacological role along this axis remains poorly defined. This review systematically delineates the pathological contribution of the gut microbiota–inflammation–depression axis to tumor development, explores the multi-node regulatory potential of β-elemene on this axis, and identifies core molecular targets and signaling pathways via supplementary bioinformatic analysis. Relevant English and Chinese publications from database inception through 2026 were retrieved from PubMed, Web of Science Core Collection and CNKI; eligible studies were screened, and an integrated analysis was performed incorporating network pharmacology and molecular docking data. The results identified a total of 125 overlapping therapeutic targets were identified, and 13 core hub targets were finally obtained, among which STAT3, MTOR, PPARA, EGFR and NR3C1 were defined as the key potential targets of β-elemene. The PI3K-Akt signaling pathway emerged as the most significantly enriched pathway, serving as a pivotal signaling hub bridging gut barrier homeostasis, inflammatory cascades, and neurofunctional modulation. However, current research still has limitations. Clinical evidence supporting the antidepressant efficacy of β-elemene is lacking, its microbiota-regulating and anti-inflammatory mechanisms remain mostly at the stage of basic research, and constraints such as poor aqueous solubility and inadequate targeted delivery hinder the clinical translation and application of this integrative therapeutic strategy.
Chen et al. (Wed,) studied this question.