Study on the dose-efficacy relationship of Dahuang (Rhei Radix et Rhizoma) based on fuzzy association rules

Abstract

Objective

To investigate the dose-efficacy relationship of Dahuang (Rhei Radix et Rhizoma) using fuzzy association rules, provide scientific evidence for its precise clinical application, and establish a novel paradigm for research on the dose-efficacy relationship of Chinese materia medica (CMM).

Methods

A total of 2 449 prescriptions with Dahuang (Rhei Radix et Rhizoma) as the sovereign drug and with explicit dosage records were screened from the Traditional Chinese Medicine Ancient Prescription Database. Efficacy terminology was standardized and consolidated, dosage units were uniformly converted into metric units (g) according to their respective dynasties, and a Dahuang (Rhei Radix et Rhizoma) dose-efficacy prescription database was constructed. The prescriptions were divided into six groups according to patient age and route of administration; the internal-use adults group (n = 1 828), the internal-use children group (n = 280), and the external-use adults group (n = 272) were included in the analysis, while the other three groups were excluded owing to insufficient sample sizes. Dosages were partitioned into small, medium, and large fuzzy intervals at an approximate equal-frequency ratio of 2 : 6 : 2, triangular membership functions were defined to fuzzify the dosage data, and a fuzzy association rule mining algorithm was applied to mine the dose-efficacy relationships.

Results

The dosage of Dahuang (Rhei Radix et Rhizoma) exhibited a decreasing trend across dynasties, with a relatively large dose being commonly used during the Han and Tang-Song periods, gradually approaching modern clinical dosages from the Ming-Qing period onward. In the internal-use adults group, small doses were mainly associated with reducing swelling, unblocking the channels, descending Qi, resolving toxins, and enhancing medicinal potency; medium doses were associated with clearing heat, purging, and dispersing wind; and large doses were associated with breaking blood, attacking heat, and expelling pus. In the external-use adults group, small doses were mainly associated with reducing swelling, relieving pain, and promoting tissue regeneration; medium doses were associated with clearing heat and drying dampness, dissipating masses, and reducing swelling; and large doses were associated with expelling pus and promoting tissue regeneration, healing sores, and strengthening teeth. In the internal-use children group, small doses were dominated by clearing heat, resolving toxins, and purging; medium doses centered on relieving jaundice, eliminating sores, and clearing lung heat; and large doses leaned toward killing parasites, clearing phlegm, and eliminating food accumulation.

Conclusion

Using fuzzy association rules, this study quantitatively elucidated the dose-efficacy relationships of Dahuang (Rhei Radix et Rhizoma) for internal and external use, revealing lower dosages and distinct efficacy emphases in children versus adults. The method effectively handles the continuity and fuzziness of CMM dosage data, providing a replicable and scalable paradigm for quantitative dose-efficacy research and advancing the precise clinical application of Dahuang (Rhei Radix et Rhizoma).