Objectives: This study aimed to further explore the efficacy and safety of Danggui Buxue Tang (DBT), a simple herbal formula, for improving the quality of life of women suffering from menopausal symptoms. Methods: A third clinical trial to determine the clinical efficacy of high-dose DBT for a period of 12 weeks was carried out. The standard Menopause-Specific Quality of Life (MENQOL) assessment chart was used for the evaluation. Safety was defined as an absence of direct estrogenic effects, serum inflammatory cytokines. Notably, interleukin IL-6, IL-8 and tumor necrosis factor TNF-α, known to be directly related to estrogenic reactions in menopause studies, were monitored. Results: The third clinical trial indicated an overall improvement in the four domains of MENQOL, offering further proof of the efficacy of DBT demonstrated in the two previous trials. The serial checks of the three cytokines related to estrogen activities did not show either upward or downward trends. The haphazard behavior reactions of the three cytokines offered indirect indications that DBT improved the MENQOL independently from estrogen activities. Conclusions The three clinical trials using DBT to relieve menopausal syndrome have offered solid evidence for its efficacy. The uncertainty regarding whether the “phytoestrogen” contained in DBT had bioactivities similar to estrogen was alleviated through the confirmation that no strict estrogenic bioactivities were observed. The issue of safety was further clarified via laboratory platform studies on DBT, which not only showed the lack of similarity with estrogen actions but also confirmed the value of combining the two herbs in the classic formula.

The herb pair is the simple and exquisite experience summary accumulated by generations of traditional Chinese medicine (TCM) experts in the process of long-term herbal prescription for curing diseases. Although it is only a combination of two herbs, it is cleverly matched and properly proportioned, which can well interpret TCM characteristics of "great combination and artful application". Moreover, the herb pair is an intermediate point between single herb and several TCM formulae, which implicates certain regularity and some connotation of many TCM formulae for diagnosis and treatment based on an overall analysis of the illness and the patient's condition. Our team has long been focusing on the complexity of drug interactions and the diversity of TCM components to carry out systematic research on herb pair by using modern scientific and technological knowledge and approaches. As results, a series of modern research approaches and strategies formed for the compatibility effect and bio-active components of the herb pair. By representing the principles and application characteristics of these approaches, this paper provides important support for elucidating scientific connotation of compatibility regularity of herb pairs and application of formulae optimization, as well as explorative ideas and approaches for modern research on other herb pairs.