Guizhi Fuling Formulation: A review on chemical constituents, quality control, pharmacokinetic studies, pharmacological properties, adverse reactions and clinical applications

Ethnopharmacological relevance: Guizhi Fuling Formulation (GF), composed of Cinnamomi Ramulus, Poria, Paeoniae Radix, Moutan Cortex, and Persicae Semen, was first recorded as a pill in the Traditional Chinese Medicine (TCM) classical book Synopsis of Prescriptions of the Golden Chamber written by Zhang Zhongjing in the Eastern Han Dynasty (25-220 CE). As a TCM prescription, it functions to improve blood circulation, reduce blood stasis and eliminate abdominal lumps. Originally used to treat the restlessness of pregnancy due to a mass, it is now also effective in treating gynecological illnesses and various tumors such as cervical cancer, ovarian cancer, and others. With the expansion of clinical applications, GF was developed into different dosage forms, including Guizhi Fuling Pill (GFP), Guizhi Fuling Capsule (GFC), Guizhi Fuling Tablet (GFT), Guizhi Fuling Granule (GFG), and Guizhi Fuling Decoction (GFD). Different dosage forms of GF play an important role in clinical treatment. Aim of the review: To systematically analyze and summarize the research findings concerning the chemical constituents, quality control, pharmacokinetic studies, pharmacological properties, adverse reactions, and clinical applications of GF, so as to point out the problems existing in the current research and provides opinions for future study. Materials and methods: The relevant literatures were collected from classical TCM books and a variety of databases, including China National Knowledge Infrastructure, WanFang Data, PubMed, SpringerLink, Web of Science, and Google Scholar. All eligible studies are analyzed and summarized in this review. Results: There are some problems for GF: the quality control system is not perfect, the study of pharmacokinetics is not comprehensive, the explanation of pharmacological mechanism is insufficient, and the clinical safety has not been fully verified. A few of research directions for future research are proposed: (i) to establish the method of characteristic components combined with bioassay and multi-index content determination to improve the quality evaluation; (ii) to elucidate pharmacokinetic studies based on human pharmacokinetic characteristics and interaction with intestinal microbiota; (iii) to carry out pharmacological mechanism studies at whole, organ, cellular and molecular levels; (iv) to reconfirm safety of various dosage forms of GF based on large-scale clinical studies. Conclusions: GF is extremely valuable in drug research and in clinical treatment especially for gynecological diseases. However, there are also some issues. Future efforts should focus on strengthening quality control, clarifying pharmacological and pharmacokinetic processes, and reconfirming clinical safety.