Research progress on targeting autophagy pathways with medicinal plants and their active metabolites for the treatment of heart failure.

Despite the therapeutic promise of natural plants in preclinical models, their clinical value for heart failure (HF) remains unconfirmed and requires rigorous validation through well-designed trials. HF severely impairs quality of life, and natural plant therapies-known for their multi-metabolites and multi-target effects-have been explored as potential treatments via modulation of autophagy, inhibition of inflammation, and reduction of oxidative stress. However, several critical issues remain unresolved: the broad-spectrum activity raises concerns about target specificity and off-target effects. Current evidence largely relies on correlative observations rather than direct mechanistic validation. The assumption that natural products are inherently safer than synthetic drugs is flawed due to dose-dependent toxicity and the absence of long-term clinical data. And the reductionist isolation of active metabolites may overlook the synergistic actions of whole herbal preparations. Moreover, while modulation of multiple autophagy-related pathways is theoretically superior, existing data stem primarily from basic or observational studies rather than from rigorously designed randomized controlled trials. Chinese herbal formulas exhibit "multi-metabolite, multi-target, multi-pathway" actions that cannot be explained by a single pathway, and the transition from traditional use to evidence-based therapy faces challenges in standardization, quality control, and dose optimization. This review critically examines the ethnopharmacological use of natural plants in HF through autophagy regulation, drawing on traditional medicine classics and databases including PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, and Wanfang. Our key findings indicate that medicinal plants offer advantages in multi-target regulation and safety, but these potential benefits must be interpreted with caution. Claims of "significant clinical efficacy" should not be overgeneralized. Thus, rigorous methodologies and large-scale clinical trials are urgently needed to confirm whether natural plant therapies can truly translate into tangible benefits for HF patients.