Phytochemical Insights into Panax Genus Metabolites: Evidence-Based Fatigue Intervention via Ethnopharmacological and Biomedical Perspectives

Traditional Chinese Medicine (TCM) has a longstanding history in the treatment of fatigue-related conditions, and is increasingly recognized as a foundation for novel therapeutic approaches. The Panax genus, extensively utilized in the fundamental TCM principles to enhance vitality, modulate immune function, and stimulate Yang energy, is a key resource in managing both physiological and pathological fatigue. This study provides a comprehensive synthesis of recent advancements in plant-derived metabolites from various Panax species with an emphasis on their structural diversity and structure-activity relationships. Notably, this represents the first systematic exploration of Panax metabolites with potential antifatigue effects. A systematic literature review was conducted using major scientific databases such as PubMed, Google Scholar, and ScienceDirect. The search query "(scientific name of herbal medicine in the Panax genus) AND ("antifatigue")" was employed. Additionally, classical herbals, botanical literature, and pharmacopoeias were reviewed to contextualize the findings. Comprehensive analysis of 105 studies elucidated 16 predominant metabolites exhibiting antifatigue activity. These metabolites primarily originated from Panax ginseng, Panax quinquefolium, and Panax notoginseng. Ginsenosides Rb1 and Rg1 demonstrated the most substantial pharmacological efficacy in experimental models, in particular by ameliorating metabolic perturbations and mitigating oxidative stress in vivo. Clinical trials predominantly relied on subjective patient-reported measures, such as the Multidimensional Fatigue Inventory (MFI) and Visual Analogue Scale (VAS), and yielded largely positive outcomes. These findings substantiate fundamental TCM principles and reinforce the therapeutic potential of Panax species in fatigue management. The integration of traditional knowledge with contemporary biomedical research enhances the understanding and clinical applicability of Panax species in addressing fatigue-related disorders.