Er-xian Decoction: A comprehensive review on chemical constituents, quality control, pharmacokinetics, pharmacological properties and clinical applications

BACKGROUND: Er-xian Decoction (EXD) is a renowned traditional Chinese medicine (TCM) formula developed by Professor Bo-Ne Zhang in the 1950s for managing menopausal syndrome. It comprises six herbs, including Curculiginis Rhizoma, Epimedii Folium, Morindae Officinalis Radix, Angelicae Sinensis Radix, Phellodendri Chinensis Cortex, and Anemarrhenae Rhizoma, has demonstrated broad pharmacological effects, including estrogen-like activity, anti-osteoporosis, anti-aging, and anti-depression properties, making it applicable for conditions like osteoporosis, premature ovarian failure, and hypertension. PURPOSE: This review aims to comprehensively summarize the chemical constituents, quality control, pharmacokinetics, pharmacological properties, and clinical applications of EXD seeking to elucidate the multi-component, multi-target mechanisms underlying its therapeutic effects, and provide insights for quality standardization, and explore future research directions to expand its clinical use, particularly in age-related and metabolic diseases. METHODS: The review adhered to systematic literature search principles, drawing data from databases such as PubMed, CNKI, and Web of Science using keywords like "Er-xian Decoction," "chemical composition," and "pharmacology." Data were organized into narrative and tabular formats, with chemical structures illustrated using tools like InDraw. Information spanned publications from 1965 to 2025, ensuring comprehensive coverage of EXD's phytochemistry and bioactivity. RESULTS: Phytochemical studies have identified 128 compounds in EXD, including alkaloids, flavonoids, phenolic acids, and terpenes, which contribute to its diverse bioactivities. Quality control relies on quantifying markers like icariin and berberine, though extraction methods significantly influence component levels. Pharmacokinetic studies in rats have shown that EXD's components are absorbed systemically and distributed to organs like kidneys and ovaries, with flavonoids exhibiting prolonged retention. Pharmacologically, EXD regulates the hypothalamic-pituitary-gonadal (HPG) axis, exhibits antioxidant and anti-osteoporosis effects via pathways like PI3K/Akt and Nrf2, and demonstrates efficacy in menopausal syndrome, osteoporosis, and cardiovascular protection. Clinically, EXD and its modifications, often combined with hormone therapy, improve symptoms in patients with menopausal syndrome, osteoporosis, and premature ovarian failure, based on randomized trials involving thousands of patients. CONCLUSION: EXD represents a holistic TCM approach with synergistic multi-target actions. Future research should focus on identifying active constituents, developing integrated quality control systems, elucidating pharmacokinetic and combination therapy mechanisms, and conducting evidence-based clinical trials to optimize personalized treatments. This will advance EXD from empirical use to precision medicine.